Hot Flashes in Womens Health

1. Hot Flashes in Women's Health Elizabeth Cerceo, MD Assistant Program Director Internal Medicine Cooper University Hospital

2. Goals of Talk Review some common clinical topics in womens health. Update on current screening guidelines in a variety of women's health issues. Highlight some of the years significant papers in the field. Q/A

3. Goals of Talk Contraception/Emergency Contraception Abnormal Uterine Bleeding Preconception care Menopause/HRT STD screening Cervical cancer screening Breast masses Breast cancer screening/BRCA Ovarian cancer screening Osteoporosis

4. Contraception

5. Contraception Almost 50% of pregnancies in US (~3.2 million) are unintended. Almost 50% women ages 15-44 will experience at least one unintended pregnancy. Urine pregnancy tests are accurate at time of missed period. Chance of pregnancy increases beginning 5 days before ovulation and drops to 0 day after ovulation. American adolescents are less likely to become pregnant now than a decade ago. However, this is not a reason for complacency or diminished concern. International statistics demonstrate that a 15- to 19-year-old American girl is still far more likely to become pregnant and give birth than her counterpart in other western developed countries. Among girls this age, the birthrate is approximately 5% in the United States compared to less than 1% in France and Sweden, 2% in Canada, and 3% in Great Britain. This is not because 15- to 19-year-old American girls are more likely to be sexually active. Among girls this age, the rate of sexual activity is approximately 51% in the United States compared to 41% in France, 51% in Canada, 61% in Great Britain. It is because 15- to 19-year-old American girls are less likely to use contraception. The proportion who failed to use contraception at last intercourse was approximately 20% in the United States compared to 12% in France, 7% in Sweden, and 4% in Great Britain. 15- to 19-year-old American girls are also less likely to use modern methods of contraception. Among sexually experienced girls this age, the proportion who use modern methods of contraception � oral contraceptives, injectables, implants and intrauterine methods � is approximately 42% in the United States compared to 52% in Sweden, 60% in France, 65% in Canada, and 70% in Great Britain. American adolescents are less likely to become pregnant now than a decade ago. However, this is not a reason for complacency or diminished concern. International statistics demonstrate that a 15- to 19-year-old American girl is still far more likely to become pregnant and give birth than her counterpart in other western developed countries. Among girls this age, the birthrate is approximately 5% in the United States compared to less than 1% in France and Sweden, 2% in Canada, and 3% in Great Britain. This is not because 15- to 19-year-old American girls are more likely to be sexually active. Among girls this age, the rate of sexual activity is approximately 51% in the United States compared to 41% in France, 51% in Canada, 61% in Great Britain. It is because 15- to 19-year-old American girls are less likely to use contraception. The proportion who failed to use contraception at last intercourse was approximately 20% in the United States compared to 12% in France, 7% in Sweden, and 4% in Great Britain. 15- to 19-year-old American girls are also less likely to use modern methods of contraception. Among sexually experienced girls this age, the proportion who use modern methods of contraception � oral contraceptives, injectables, implants and intrauterine methods � is approximately 42% in the United States compared to 52% in Sweden, 60% in France, 65% in Canada, and 70% in Great Britain.

6. Contraception Used both for protection against unwanted pregnancy and a variety of other medical problems including dysmenorrhea, anemia, and acne. New contraceptive options, including a new progestin, a patch, a once a month shot, a vaginal ring and an experimental device for surgery free sterilization. New contraceptives afford women more options and fewer adverse effects. BP monitoring key during the first few months after starting OCPs. Many commonly used drugs interact with OCPs. Essure = soft, flexible inserts into fallopian tubes. During the 3 months following the procedure, pt forms a natural barrier that prevents sperm from reaching the egg. During this period, you must continue using another form of birth control. After 3 months, test with hysterosalpingogram to confirm fallopian tubes are completely blocked. Essure = soft, flexible inserts into fallopian tubes. During the 3 months following the procedure, pt forms a natural barrier that prevents sperm from reaching the egg. During this period, you must continue using another form of birth control. After 3 months, test with hysterosalpingogram to confirm fallopian tubes are completely blocked.

7. Implanon= alternative to a cyclic method of contraception or an intrauterine device. = lasts 3 yrs, effects over 3 months after removal = 100% bioavailable within hours and undetectable within 1 week of removal = The insertion site is the inner side of the nondominant arm at a level six to eight inches above the elbow crease. Although the implant is inconspicuous, both the clinician and patient should be able to feel it once it has been inserted. = inhibition of ovulation through the prevention of the midcycle LH peak and thickens cervical mucus = irregular bleeding most common in first 8 monthsImplanon= alternative to a cyclic method of contraception or an intrauterine device. = lasts 3 yrs, effects over 3 months after removal = 100% bioavailable within hours and undetectable within 1 week of removal = The insertion site is the inner side of the nondominant arm at a level six to eight inches above the elbow crease. Although the implant is inconspicuous, both the clinician and patient should be able to feel it once it has been inserted. = inhibition of ovulation through the prevention of the midcycle LH peak and thickens cervical mucus = irregular bleeding most common in first 8 months

9. Selecting the right pill Always attempt to start with a low dose estrogen (less than 50ug). Anticipate side effects during the first few months. Typical estrogenic side effects: nausea, bloating, breast tenderness Typical androgenic effects: acne, weight gain, hirsuitism Triphasic pills (different dose) have no distinct advantage over monophasic pills (same dose every day). Obtain history about prior OCP use. www.fpnotebook.com good resource on OCP side effect profiles and what to switch to.

10. Contraindications to combination contraceptives Ex. pills, the patch, or the vaginal ring <6 weeks postpartum and breastfeeding Arterial cardiovascular disease, ischemic heart disease, CVA, valvular heart disease, or vascular disease HTN (>160 mm Hg systolic/>100 mm Hg diastolic) DM with related eye, liver, or nerve diseases H/o VTE =15 cigarettes/day Headaches with auras Cirrhosis, active viral hepatitis, or liver tumors Bone mineral density decreases have been documented with the use of injectable contraceptives; some but not complete recovery of bone mineral density has been documented after discontinuation. FDA has issued a warning that a woman should use Depo-Provera� (depot-medroxyprogesterone acetate) for more than 2 years only if other contraceptive methods are inadequate for her. Bone mineral density decreases have been documented with the use of injectable contraceptives; some but not complete recovery of bone mineral density has been documented after discontinuation. FDA has issued a warning that a woman should use Depo-Provera� (depot-medroxyprogesterone acetate) for more than 2 years only if other contraceptive methods are inadequate for her.

11. Cancer risk and contraception Large case-control studies have demonstrated that oral contraceptive use is associated with a decreased risk of cervical, ovarian, and uterine cancer. Data on the risk of breast cancer with oral contraceptive use are conflicting. Analyses indicate a slight increased risk of breast cancer with oral contraceptive use, whereas a case-control study conducted in several cities in the United States found no increased risk in current or former users. There are no data regarding the effects of the contraceptive patch and vaginal ring on cancer. Overall, risks associated with these methods are expected to be comparable to other methods that contain similar hormones; however, patch users are exposed to increased levels of estrogen when compared to oral contraceptive users. Barrier methods, such as the condom or diaphragm, protect against cervical cancer, most likely because they block infection from penetrating the cervix. Small case-control studies indicate that use of injectable depot-medroxyprogesterone acetate is associated with protection against uterine cancer and without an increased risk of cervical cancer. Copper intrauterine devices and the levonorgestrel-releasing intrauterine system are associated with a decreased risk of cervical and endometrial cancer. Tubal sterilization is associated with a decreased risk of cervical, uterine, and ovarian cancer. Large case-control studies have demonstrated that oral contraceptive use is associated with a decreased risk of cervical, ovarian, and uterine cancer. Data on the risk of breast cancer with oral contraceptive use are conflicting. Analyses indicate a slight increased risk of breast cancer with oral contraceptive use, whereas a case-control study conducted in several cities in the United States found no increased risk in current or former users. There are no data regarding the effects of the contraceptive patch and vaginal ring on cancer. Overall, risks associated with these methods are expected to be comparable to other methods that contain similar hormones; however, patch users are exposed to increased levels of estrogen when compared to oral contraceptive users. Barrier methods, such as the condom or diaphragm, protect against cervical cancer, most likely because they block infection from penetrating the cervix. Small case-control studies indicate that use of injectable depot-medroxyprogesterone acetate is associated with protection against uterine cancer and without an increased risk of cervical cancer. Copper intrauterine devices and the levonorgestrel-releasing intrauterine system are associated with a decreased risk of cervical and endometrial cancer. Tubal sterilization is associated with a decreased risk of cervical, uterine, and ovarian cancer.

12. Myths and misconceptions about contraceptives Oral contraceptives Cause cancer Cause blood clots Are associated with weight gain Should not be taken by women >35 yo Build up in a woman�s body b/c daily use Injectable contraceptives Cause infertility Condoms Can get lost in a woman�s body Lessen sexual pleasure Provide extra protection if 2 are worn simultaneously The low-dose oral contraceptives available today are not associated with an increased risk of cancer or of blood clots, except in rare instances. Women are more susceptible to blood clots should not use oral contraceptives. Some women may experience weight gain from the use of oral contraceptives and other hormonal methods. Switching to another oral contraceptive and implementing a regimen of diet and exercise can minimize the amount of weight gained. Women over 35 years of age who do not smoke or do not have risk factors for heart attack or stroke can safely use the newer formulations of oral contraceptives. Some women believe that they need to periodically stop taking oral contraceptives because they �build up in the body.� Some women who use the injectable contraceptive depot-medroxyprogesterone acetate may experience a delay in becoming pregnant; clinical data indicate that the average delay is 6 months following the last injection. Since an injection is expected to be effective for 13 weeks, such a delay would not be unreasonable. The low-dose oral contraceptives available today are not associated with an increased risk of cancer or of blood clots, except in rare instances. Women are more susceptible to blood clots should not use oral contraceptives. Some women may experience weight gain from the use of oral contraceptives and other hormonal methods. Switching to another oral contraceptive and implementing a regimen of diet and exercise can minimize the amount of weight gained. Women over 35 years of age who do not smoke or do not have risk factors for heart attack or stroke can safely use the newer formulations of oral contraceptives. Some women believe that they need to periodically stop taking oral contraceptives because they �build up in the body.� Some women who use the injectable contraceptive depot-medroxyprogesterone acetate may experience a delay in becoming pregnant; clinical data indicate that the average delay is 6 months following the last injection. Since an injection is expected to be effective for 13 weeks, such a delay would not be unreasonable.

13. Myths and Misconceptions about Intrauterine Contraceptives (IUDs) IUDs are abortifacients IUDs cause ectopic pregnancies and, therefore, cannot be used in women with a history of ectopic pregnancy IUDs cause PID IUDs cannot be used in nulliparous women IUDs cause infertility IUDs can leave the uterus and travel through a woman's body � IUDs are not abortifacients; their primary mechanism of action is to prevent fertilization. � IUDs do not increase the risk of ectopic pregnancy but are highly effective in preventing all types of pregnancy. Should a pregnancy occur, it is more likely to be ectopic than intrauterine. Although IUD use in women with a previous ectopic pregnancy is appropriate, this is an off-label use. According to the Medical Eligibility Criteria for Contraceptive Use developed by the World Health Organization (WHO), a previous ectopic pregnancy is a condition for which there are no restrictions (risk category 1). � IUDs do not increase the risk of PID, but PID can occur within the first 20 days after insertion. For this reason, patients should be evaluated for the presence of infection, as well as for proper IUD placement, during the clinic visit immediately after the first postinsertion menstrual period. According to the WHO Medical Eligibility Criteria for Contraceptive Use, PID is a condition that precludes the use of an IUD (risk category 4), but a past occurrence of PID is a condition for which the advantages of using intrauterine contraception generally outweigh the theoretical or proven risks (risk category 2). � A four-year study found that the failure and expulsion rates for IUDs were lower for nulliparous women than for parous women. Another study that evaluated three types of IUDs in nulliparous women also found low failure and expulsion rates. According to the WHO Medical Eligibility Criteria for Contraceptive Use, nulliparity is a condition for which the advantages of using intrauterine contraception generally outweigh the theoretical or proven risks (risk category 2). � A case-control study found that tubal infertility in nulliparous women was not linked to a history of IUD use but was significantly associated with the presence of antibodies to Chlamydia. WHO reviewed the available evidence and concluded that most of the data concerning the return to fertility after IUD use are reassuring. � IUDs are not abortifacients; their primary mechanism of action is to prevent fertilization. � IUDs do not increase the risk of ectopic pregnancy but are highly effective in preventing all types of pregnancy. Should a pregnancy occur, it is more likely to be ectopic than intrauterine. Although IUD use in women with a previous ectopic pregnancy is appropriate, this is an off-label use. According to the Medical Eligibility Criteria for Contraceptive Use developed by the World Health Organization (WHO), a previous ectopic pregnancy is a condition for which there are no restrictions (risk category 1). � IUDs do not increase the risk of PID, but PID can occur within the first 20 days after insertion. For this reason, patients should be evaluated for the presence of infection, as well as for proper IUD placement, during the clinic visit immediately after the first postinsertion menstrual period. According to the WHO Medical Eligibility Criteria for Contraceptive Use, PID is a condition that precludes the use of an IUD (risk category 4), but a past occurrence of PID is a condition for which the advantages of using intrauterine contraception generally outweigh the theoretical or proven risks (risk category 2). � A four-year study found that the failure and expulsion rates for IUDs were lower for nulliparous women than for parous women. Another study that evaluated three types of IUDs in nulliparous women also found low failure and expulsion rates. According to the WHO Medical Eligibility Criteria for Contraceptive Use, nulliparity is a condition for which the advantages of using intrauterine contraception generally outweigh the theoretical or proven risks (risk category 2). � A case-control study found that tubal infertility in nulliparous women was not linked to a history of IUD use but was significantly associated with the presence of antibodies to Chlamydia. WHO reviewed the available evidence and concluded that most of the data concerning the return to fertility after IUD use are reassuring.

14. Emergency Contraception Defined as the prevention of pregnancy within 72 hours of unprotected intercourse or failure of a contraceptive method. Evidence also indicates that ECPs are still effective between 72hrs and 120hrs but efficacy reduced especially after 96hrs. Unknown efficacy after 120hrs. Extremely effective, low potential for adverse effects. Very under-prescribed because physicians do not know enough about it and or uncomfortable about prescribing it. Ideally, pts should take levonorgestrel- only or combined estrogen-progestogen ECPs as early as possible after unprotected intercourse, within 72 hrs.

15. Regimens Preferred regimen, 1.50mg of levonorgesterol in a single dose. Alternatively, levonorgesterol in 2 doses (0.75mg q12h x 2 doses) 3rd option is combined ECPs in 2 doses (ethinyl estradiol 100ug plus levonorgesterol 0.50mg q12h x 2 doses). 40% have severe n/v. Studies indicate that a woman is more likely to use ECPs after unprotected intercourse if she has an advance supply

16. FDA-approved regimens The Preven kit (Ethinyl estradiol 50ug and Levonorgesterol 25ug) 2pills q12hrs x 2. Plan B kit-progestin only. One tablet followed by a second dose 12 hrs later. OTC $35-60. Pharmacist may legally refuse to dispense. Mifepristone: single 600 mg dose Copper IUD Mifepristone followed by misoprostol: Mifepristone causes placenta to separate from endometrium, increases uterine CTX. Misoprostol po within 6-48 hours of mifepristone which causes uterine contractions so that your body passes the uterine contents.Mifepristone followed by misoprostol: Mifepristone causes placenta to separate from endometrium, increases uterine CTX. Misoprostol po within 6-48 hours of mifepristone which causes uterine contractions so that your body passes the uterine contents.

17. Abnormal Uterine Bleeding Menorrhagia � Bleeding occurs at normal intervals but is prolonged or excessive Metrorrhagia - Irregular bleeding between menstrual cycles Menometrorrhagia � Irregular, noncyclic bleeding that is prolonged or excessive Polymenorrhea/oligomenorrhea � Bleeding interval is less than 21 days (poly) or greater than 35 days (oligo) Hypermenorrhea/hypomenorrhea � Amount of menses is abnormally high (hyper) or low (hypo)

18. Menstrual Cycle Menstrual cycle lasts ~ 28 days (range 21-35 days) Menstruation lasts 3 to 6 days with avg blood loss 35 mL Chronic menstrual blood loss of > 80 mL per cycle leads to anemia Patients measure abnormal bleeding by: An increase of = 2 pads or tampons/day Menstrual bleeding lasting 3 days longer than usual Blood clots that have increased in size and/or number Sanitary product needs that interfere with their usual activities Although patient perception of blood loss does not usually correlate with the actual quantity of blood lost, any abnormal bleeding reported by the patient warrants investigation. The blood on toilet tissue or a sanitary napkin may not be uterine: Check urinalysis for blood that may be caused by: ? Cystitis ? Urinary tract stones ? Bladder cancer Check stool for hidden blood (guaiac) that may be caused by: ? Colon polyps ? Diverticula ? Gastrointestinal cancer ? Gastroduodenal ulcers ? HemorrhoidsAlthough patient perception of blood loss does not usually correlate with the actual quantity of blood lost, any abnormal bleeding reported by the patient warrants investigation. The blood on toilet tissue or a sanitary napkin may not be uterine: Check urinalysis for blood that may be caused by: ? Cystitis ? Urinary tract stones ? Bladder cancer Check stool for hidden blood (guaiac) that may be caused by: ? Colon polyps ? Diverticula ? Gastrointestinal cancer ? Gastroduodenal ulcers ? Hemorrhoids

19. Differential of Abnormal Uterine Bleeding Pregnancy: >1/3 have bleeding during the first 20 weeks Pregnancy-related conditions: Ectopic pregnancy; Trophoblastic disease; Miscarriage � incomplete, threatened, or missed abortion Thyroid disease Metrorrhagia -> hypothyroidism Oligomenorrhea -> hyperthyroidism Polycystic ovary syndrome Associated with anovulation -> oligomenorrhea -> buildup of endometrium and menorrhagia Adrenal hyperplasia/Cushing disease Hematologic disorders Up to 20% of women with menorrhagia have an underlying bleeding problem, most commonly von Willebrand disease type 1. Renal disease Liver disease Metrorrhagia is typically associated with hypothyroidism, whereas oligomenorrhea is associated with hyperthyroidism. A thyroid panel can be used to eliminate thyroid diseases as a cause of uterine bleeding. Hematologic deficiencies such as von Willebrand disease, prothrombin deficiency, leukemia, and ITP have been linked to uterine bleeding. Polycystic ovary syndrome is associated with anovulation, which often results in oligomenorrhea, which in turn leads to menorrhagia due to buildup of the endometrium.Metrorrhagia is typically associated with hypothyroidism, whereas oligomenorrhea is associated with hyperthyroidism. A thyroid panel can be used to eliminate thyroid diseases as a cause of uterine bleeding. Hematologic deficiencies such as von Willebrand disease, prothrombin deficiency, leukemia, and ITP have been linked to uterine bleeding. Polycystic ovary syndrome is associated with anovulation, which often results in oligomenorrhea, which in turn leads to menorrhagia due to buildup of the endometrium.

20. Differential of Abnormal Uterine Bleeding Infections Chlamydia Benign abnormalities Cervical or endometrial polyps Submucosal uterine leiomyomata Premalignant/malignant lesions of cervix, endometrium, and ovary Trauma/irritation Sexual assault Presence of a foreign body

21. Differential of Abnormal Uterine Bleeding: Meds and devices OCPs IUDs HRT SSRI/antipsychotics � increase prolactin Anticoagulants Steroids Herbal supplements, including ginseng, gingko, soy supplements The diagnosis of abnormal uterine bleeding involves elimination of other causes, such as a side effect of medication or iatrogenic factors. Use of combination and progestin-only oral contraceptives or hormone therapy may result in menstrual irregularities. The copper-releasing intrauterine device also increases menstrual bleeding in some women. Antidepressants and antipsychotics often increase prolactin levels, resulting in menstrual irregularities. The diagnosis of abnormal uterine bleeding involves elimination of other causes, such as a side effect of medication or iatrogenic factors. Use of combination and progestin-only oral contraceptives or hormone therapy may result in menstrual irregularities. The copper-releasing intrauterine device also increases menstrual bleeding in some women. Antidepressants and antipsychotics often increase prolactin levels, resulting in menstrual irregularities.

22. Ancillary Lab Testing Anovulatory bleeding is a common occurrence in young women at the time of menarche because of an immature hypothalamic-pituitary axis. A blood dyscrasia (i.e., von Willebrand disease or prothrombin deficiency) or platelet dysfunction (i.e., leukemia, ITP) in adolescents may cause heavy bleeding and should be ruled out by performing a complete blood count with a platelet count. In addition, one group recommends that the prothrombin time (extrinsic pathway), the activated partial thromboplastin time (intrinsic pathway), thrombin time, and the level of fibrinogen be measured. Consultation with a hematologist may be required if a coagulation defect is evident.Anovulatory bleeding is a common occurrence in young women at the time of menarche because of an immature hypothalamic-pituitary axis. A blood dyscrasia (i.e., von Willebrand disease or prothrombin deficiency) or platelet dysfunction (i.e., leukemia, ITP) in adolescents may cause heavy bleeding and should be ruled out by performing a complete blood count with a platelet count. In addition, one group recommends that the prothrombin time (extrinsic pathway), the activated partial thromboplastin time (intrinsic pathway), thrombin time, and the level of fibrinogen be measured. Consultation with a hematologist may be required if a coagulation defect is evident.

23. When to biopsy

24. Medical Therapies for Heavy Uterine Bleeding Combination oral contraceptives Progestins Cyclic or continuous administration Levonorgestrel intrauterine system NSAIDs If bleeding does not improve with NSAIDs, consider a coagulation disorder, or liver or kidney disease Danazol $$$ and androgenic side effects Gonadotropin-releasing hormone agonists $$$ and bone loss due to hypoestrogenemia Antifibrinolytics (tranexamic acid) are very effective but not available in US; ongoing trial from 2007. Medical treatment should be considered as a frontline treatment for abnormal uterine bleeding to avoid surgery. Combination and progestin-only oral contraceptives are often used to regulate the menstrual cycle and may reduce blood loss. The levonorgestrel intrauterine system decreases menstrual blood loss in many women, resulting in amenorrhea in approximately 15%. NSAIDs reduce blood loss but are less effective than other medical therapies. Although danazol and gonadotropin-releasing hormone agonists are effective at reducing blood loss, long-term use is limited by the risk of serious side effects and by the high cost. Specifically, long term use of danazol is associated with androgenic side effects, and the use of gonadotropin-releasing hormone agonists may result in bone loss due to hypoestrogenemia. Nevertheless, these agents may be used to promote endometrial thinning before endometrial ablation.Medical treatment should be considered as a frontline treatment for abnormal uterine bleeding to avoid surgery. Combination and progestin-only oral contraceptives are often used to regulate the menstrual cycle and may reduce blood loss. The levonorgestrel intrauterine system decreases menstrual blood loss in many women, resulting in amenorrhea in approximately 15%. NSAIDs reduce blood loss but are less effective than other medical therapies. Although danazol and gonadotropin-releasing hormone agonists are effective at reducing blood loss, long-term use is limited by the risk of serious side effects and by the high cost. Specifically, long term use of danazol is associated with androgenic side effects, and the use of gonadotropin-releasing hormone agonists may result in bone loss due to hypoestrogenemia. Nevertheless, these agents may be used to promote endometrial thinning before endometrial ablation.

25. Medical Therapy for Heavy Uterine Bleeding: OCPs OCPs reduce endometrial thickness as visualized by uterine US. Paucity of data on OCPs for heavy menstrual bleeding One small, RCT reported a 43% reduction in menstrual blood loss with a low-dose monophasic combined oral contraceptive (comparable to NSAIDs or danazol). Fraser IS, McCarron G. Randomized trial of 2 hormonal and 2 prostaglandin-inhibiting agents in women with a complaint of menorrhagia. Aust N Z J Obstet Gynaecol. 1991;31:66-70. This reduction was comparable to that observed with the subjects who were treated with a NSAID or danazol. Larger, randomized, controlled trials have not been conducted, precluding assessment of the effects of oral contraceptives on heavy menstrual bleeding. Although a variety of oral contraceptive formulations are available, the mechanism by which they affect heavy menstrual bleeding is unknown but may involve the estrogen dose or progestin type. Combination oral contraceptives may be a viable option for women with heavy menstrual bleeding who also wish to use contraception.This reduction was comparable to that observed with the subjects who were treated with a NSAID or danazol. Larger, randomized, controlled trials have not been conducted, precluding assessment of the effects of oral contraceptives on heavy menstrual bleeding. Although a variety of oral contraceptive formulations are available, the mechanism by which they affect heavy menstrual bleeding is unknown but may involve the estrogen dose or progestin type. Combination oral contraceptives may be a viable option for women with heavy menstrual bleeding who also wish to use contraception.

26. Medical Therapy for Heavy Uterine Bleeding: Progestins Oral progestin Administration during the luteal phase of the menstrual cycle is less effective than other methods of administration Progestin therapy for 21 days of the menstrual cycle is more effective but causes more side effects Lethaby AE, Cooke I, Rees M. Progesterone or progestogen-releasing intrauterine systems for heavy menstrual bleeding. Cochrane Database Syst Rev. 2005;(4):CD002126. During the luteal phase (days 12�26) of the menstrual cycle was less effective in decreasing menstrual blood loss when compared with danazol, tranexamic acid, and the levonorgestrel intrauterine system. Luteal phase, also referred to as 'days past ovulation' or 'DPO', is the part of the cycle that starts at ovulation and ends the day before your next period. It usually lasts about 14 days and does not vary by more than a day in each person. The luteal phase is named after the corpus luteum (Latin: "yellow body"), a structure that grows on the surface of the ovary where a mature egg was released at ovulation. The corpus luteum produces progesterone in preparing the body for pregnancy. Your luteal phase must be at least 10 days long to support pregnancy.During the luteal phase (days 12�26) of the menstrual cycle was less effective in decreasing menstrual blood loss when compared with danazol, tranexamic acid, and the levonorgestrel intrauterine system. Luteal phase, also referred to as 'days past ovulation' or 'DPO', is the part of the cycle that starts at ovulation and ends the day before your next period. It usually lasts about 14 days and does not vary by more than a day in each person. The luteal phase is named after the corpus luteum (Latin: "yellow body"), a structure that grows on the surface of the ovary where a mature egg was released at ovulation. The corpus luteum produces progesterone in preparing the body for pregnancy. Your luteal phase must be at least 10 days long to support pregnancy.

27. Medical Therapy: Injectable depot medroxyproesterone acetate Potent inhibitor of gonadotropins Bone mass may decrease with long-term use During adolescence, critical bone mass depends on adequate estrogen levels. So avoid in girls 12-14 yo.

28. Medical Therapy for Heavy Uterine Bleeding: NSAIDs NSAIDs decrease prostaglandin levels, thereby decreasing menstrual bleeding. All NSAIDs, except ibuprofen, reduced menstrual flow vs placebo Reduction in flow averaged 35 ml Pain relief was additional benefit in 75% Adverse effects: Nausea, vomiting, and indigestion Working Party for Guidelines for the Management of Heavy Menstrual Bleeding. An evidence-based guideline for the management of heavy menstrual bleeding. NZ Med J. 1999;112:174-177. Systematic review of studies evaluating NSAIDs vs placebo. Mefenamic acid, meclofenamic acid, diclofenac, ibuprofen, naproxen were compared. Another systematic review reported that NSAIDs were effective at reducing menstrual blood loss when compared with placebo but were less effective than tranexamic acid or danazol.Systematic review of studies evaluating NSAIDs vs placebo. Mefenamic acid, meclofenamic acid, diclofenac, ibuprofen, naproxen were compared. Another systematic review reported that NSAIDs were effective at reducing menstrual blood loss when compared with placebo but were less effective than tranexamic acid or danazol.

29. New treatment for menorrhagia FDA recently approved levonorgestrel intrauterine system (LNG-IUS; Mirena) for menorrhagia to suppress endometrial growth Small meta-analysis said Mirena was as effective as endometrial ablation in controlling menorrhagia for at least 2 yrs. Convenience and lower cost compared to endometrial ablation of hysterectomy FDA approves additional use for IUD Mirena to treat heavy menstrual bleeding in IUD users. [press release]. Silver Spring, MD: U.S. Food and Drug Administration; October 1 , 2009. Kilic S et al. The effect of levonorgestrel-releasing intrauterine device on menorrhagia in women taking anticoagulant medication after cardiac valve replacement. Contraception 2009 Aug; 80:152. The FDA has approved the levonorgestrel intrauterine system (LNG-IUS; Mirena) for treating heavy menstrual bleeding in women who also use the device for pregnancy prevention. In a news release, the FDA cited a manufacturer-sponsored study (recently published as an abstract) showing that, compared with medroxyprogesterone acetate, the LNG-IUS was associated with statistically significant reductions in menstrual-blood loss in parous women whose excessive bleeding did not have clear etiologies (except for small uterine fibroids in some cases). Comment: A small meta-analysis (JW Womens Health May 7 2009) showed the LNG-IUS to be as effective as endometrial ablation in controlling menorrhagia for at least 2 years. The convenience and lower cost of intrauterine device insertion compared with more-invasive interventions (endometrial ablation or hysterectomy) should make the LNG-IUS a desirable treatment option for some women. Use of the LNG-IUS to control menorrhagia in women who do not need contraception or who use other contraceptive methods remains off-label.The FDA has approved the levonorgestrel intrauterine system (LNG-IUS; Mirena) for treating heavy menstrual bleeding in women who also use the device for pregnancy prevention. In a news release, the FDA cited a manufacturer-sponsored study (recently published as an abstract) showing that, compared with medroxyprogesterone acetate, the LNG-IUS was associated with statistically significant reductions in menstrual-blood loss in parous women whose excessive bleeding did not have clear etiologies (except for small uterine fibroids in some cases). Comment: A small meta-analysis (JW Womens Health May 7 2009) showed the LNG-IUS to be as effective as endometrial ablation in controlling menorrhagia for at least 2 years. The convenience and lower cost of intrauterine device insertion compared with more-invasive interventions (endometrial ablation or hysterectomy) should make the LNG-IUS a desirable treatment option for some women. Use of the LNG-IUS to control menorrhagia in women who do not need contraception or who use other contraceptive methods remains off-label.

30. Surgical Therapy for Heavy Uterine Bleeding Dilation and curettage (acute bleeding) Stops acute uterine bleeding but is ineffective for dysfunctional uterine bleeding since blood loss returns within two cycles and frequently is increased Endometrial ablation destroys the basal layer of the endometrium First-generation techniques (assoc with fluid retention and hemorrhage; often require re-intervention) Rollerball ablation Transcervical resection Second-generation techniques (less complications � vol overload, perf but more side effects �n/v, cramping) Bipolar impedance Cryoablation Balloon ablation Hydrothermal ablation Hysterectomy Many of the endometrial ablation techniques require mechanical or hormonal pretreatment of the endometrium; the overall efficacy of the technique can be increased with the use of a preoperative endometrial thinning agent (e.g., gonadotropin-releasing hormone analogue, danazol). First-generation surgical techniques include rollerball ablation and transcervical resection. These techniques are associated with fluid retention and hemorrhage and often require reintervention. Second-generation techniques are easier to perform and are associated with fewer risks than are the first-generation approaches. The second-generation techniques employ various devices, including a thermal balloon and cryo, microwave, laser, and bipolar ablation devices. The second-generation techniques were associated with fewer complications (e.g., fluid overload, perforation, hematometra) when compared with the first-generation techniques; reports of nausea, vomiting, and cramping, however, were more likely with the second-generation techniques. Endometrial ablation is associated with a risk of perforation and does not detect abnormal pathology. As such, a preoperative endometrial biopsy is recommended. Endometrial ablation is not an option for women who wish to preserve fertility. Pregnancies after endometrial ablation procedures have occurred and are associated with an increased risk of retarded growth and preterm labor.Many of the endometrial ablation techniques require mechanical or hormonal pretreatment of the endometrium; the overall efficacy of the technique can be increased with the use of a preoperative endometrial thinning agent (e.g., gonadotropin-releasing hormone analogue, danazol). First-generation surgical techniques include rollerball ablation and transcervical resection. These techniques are associated with fluid retention and hemorrhage and often require reintervention. Second-generation techniques are easier to perform and are associated with fewer risks than are the first-generation approaches. The second-generation techniques employ various devices, including a thermal balloon and cryo, microwave, laser, and bipolar ablation devices. The second-generation techniques were associated with fewer complications (e.g., fluid overload, perforation, hematometra) when compared with the first-generation techniques; reports of nausea, vomiting, and cramping, however, were more likely with the second-generation techniques. Endometrial ablation is associated with a risk of perforation and does not detect abnormal pathology. As such, a preoperative endometrial biopsy is recommended. Endometrial ablation is not an option for women who wish to preserve fertility. Pregnancies after endometrial ablation procedures have occurred and are associated with an increased risk of retarded growth and preterm labor.

31. Fibroids Most common gynecologic tumor (20-40% of women of reproductive age. Symptoms: menorrhagia, pelvic pressure/pain, decreased fertility Risk factors: AA, Nulliparity, Obesity, EtOH Treatment: Expectant management if asx Medical: OCP if mild sc, GnRH agonists most effective Surgical: Indications include increasing size, pelvic pressure, bladder problems, anemia Hysterectomy : TAH, TVH most definitive tx Myomectomy : Recur 50-60% at 5yr, procedure of choice in women who want future pregnancies Endometrial ablation: Hysteroscopically Uterine Artery Embolization (EtOH microspheres): Could cause infertility via embolization of the arteries to the ovaries. Success 75% MRI with US heat: 15 sites in the US; 3 hours for 5 cm

32. Preconception Care

33. Preconception Care All women of childbearing age are candidates for preconception care. Every negative pregnancy test presents an opportunity. Many of the important physiologic events such as organogenesis occur way before many women are aware of their pregnancy or see a health care provider. Many women delaying pregnancy and entering pregnancy with a variety of chronic medical conditions.

36. Necessities in screening Rhesus type and antibody screen to detect antibodies potentially causing hemolytic disease of the newborn. Hgb/Hct, MCV Cervical cytology Rubella, Varicella immunity testing UA for asx bacteriuria RPR, Hep B, Chlamydia, HIV TSH At risk populations: TB, Hep C, Toxo, HSV, N. gonorrhoeae Tests for heritable conditions: CF, phenylalanine level, fragile X, Hgb electrophoresis Toxo: temperate climate countries, the prevalence of infection has declined over the last 30 years, with 10 to 50% of adults aged 15 to 45 years displaying serological evidence of past infection. Much higher rates of infection (up to 80%) are found in the tropics in communities exposed to contaminated soil, undercooked meat, or unfiltered water. Immunocompetent women infected prior to conception virtually never transmit toxoplasmosis to the fetus, although rare exceptions have been reported. Immunocompromised women (eg, women with AIDS or taking immunosuppressive medications) may have parasitemia during pregnancy despite preconceptional infection; their infants are at risk of congenital infection. Pregnant women who experience a mononucleosis-like illness, but who have a negative heterophile test, should be tested for toxoplasmosis. Maternal infection during pregnancy is most accurately diagnosed when based on a minimum of two blood samples at least two weeks apart showing seroconversion from negative to positive toxoplasma-specific IgM or IgG. Tx more effective if caught early on. Spiromycin 1 gm q8h or Pyrimethamine/sulfadiazine + leukovorin to prevent BM suppression. Tx usually till delivery.Toxo: temperate climate countries, the prevalence of infection has declined over the last 30 years, with 10 to 50% of adults aged 15 to 45 years displaying serological evidence of past infection. Much higher rates of infection (up to 80%) are found in the tropics in communities exposed to contaminated soil, undercooked meat, or unfiltered water. Immunocompetent women infected prior to conception virtually never transmit toxoplasmosis to the fetus, although rare exceptions have been reported. Immunocompromised women (eg, women with AIDS or taking immunosuppressive medications) may have parasitemia during pregnancy despite preconceptional infection; their infants are at risk of congenital infection. Pregnant women who experience a mononucleosis-like illness, but who have a negative heterophile test, should be tested for toxoplasmosis. Maternal infection during pregnancy is most accurately diagnosed when based on a minimum of two blood samples at least two weeks apart showing seroconversion from negative to positive toxoplasma-specific IgM or IgG. Tx more effective if caught early on. Spiromycin 1 gm q8h or Pyrimethamine/sulfadiazine + leukovorin to prevent BM suppression. Tx usually till delivery.

37. Necessities in screening A standard prenatal multivitamin with iron Folate before conception and throughout 1st trimester Limit caffeine, fish, excess vitamin A Review meds Air travel till 35 weeks

38. Diabetes in pregnancy HYPERGLYCEMIA IS A TERATOGEN. Preconception care key as risk of congenital anomalies directly related to A1c at conception. Fetal issues: increased risk for spontaneous abortions, fetal loss, preeclampsia, preterm delivery. Maternal issues: DM nephropathy, retinopathy, neuropathy may worsen. Preeclampsia, risk for operative delivery, cardiovascular disease, DKA. Glucose control: Goal is for lowest a1c possible w/o excessive hypoglycemia. At least 4 x daily monitoring. Fasting 65-95mg/dl 1 hr postprandial <140 2hr postprandial < 120

39. Diabetes and Pregnancy Rapid acting (lispro) does not cross placenta. No data on aspart. Long acting (glargine): no data on placenta transfer and concern for IGF binding protein. Insulin is gold standard. Oral Agents: Glyburide shown to be safe and efficacious in women with gestational diabetes. Less useful with significant insulin resistance in Type 2 DM and not routinely recommended. Metformin: does not appear to increase the risk of congenital anomalies or spontaneous losses. Crosses the placenta. Limited data on use in second or third trimesters. Metglitinides and glitazones: no data in pregnancy

40. HTN in pregnancy Most common chronic medical condition in women of childbearing age. Second leading cause of maternal mortality in U.S. BP decreases up to 16-18 wks. Then rises continuously until 38 wks when it plateaus. Methyldopa, hydralazine, and labetalol safe in pregnancy and appropriate first line meds. Pindolol, nifedipine, and clonidine are acceptable options. Diuretics are controversial. Most antihypertensive agents are compatible with breastfeeding. HCTZ, Aldomet, nifedipine, metoprolol all approved by AAP. Avoid atenolol and propanalol which are concentrated in breast milk. No evidence that HCTZ affects milk volume. Enalapril and captopril preferred ACE-inhibitors.

41. Antibiotics and pregnancy PCNs, erythromycins, and cephalosporins appear to be safe. Sulfonamides were associated with six major birth defects, including anencephaly (OR, 3.4) and hypoplastic left heart syndrome (OR, 3.2). Nitrofurantoins were associated with four birth defects (including hypoplastic left heart syndrome; OR, 4.2). Quinolones, used infrequently by women in this study, are not recommended for use during pregnancy. Crider KS et al. Antibacterial medication use during pregnancy and risk of birth defects: National Birth Defects Prevention Study. Arch Pediatr Adolesc Med 2009 Nov; 163:978. Investigators analyzed data from a national birth defects study to compare antibiotic use in 13,155 mothers of infants with at least one major birth defect and 4941 randomly selected mothers of infants without birth defects from the same geographic region and born during the same period (1997�2003). Antibiotic use was determined by telephone interview 6 weeks to 2 years after the pregnancy. Exposure to antibiotics was defined as reported use during the month before the estimated date of conception through the end of the first trimester; 14% of cases and 13% of controls used antibiotics during this interval.Investigators analyzed data from a national birth defects study to compare antibiotic use in 13,155 mothers of infants with at least one major birth defect and 4941 randomly selected mothers of infants without birth defects from the same geographic region and born during the same period (1997�2003). Antibiotic use was determined by telephone interview 6 weeks to 2 years after the pregnancy. Exposure to antibiotics was defined as reported use during the month before the estimated date of conception through the end of the first trimester; 14% of cases and 13% of controls used antibiotics during this interval.

42. Perimenopause Changing ovarian function and hormone levels that preceeds menopause by 2-8 yrs. Earliest lab finding during the transition is rise in FSH. It�s not helpful if patient is still menstruating because too many fluctuating levels. Marked by menstrual irregularities but 30% also have hot flashes and night sweats.

43. Hot Flashes Vasomotor symptoms last 6 months to 2 yrs. Risk factors: inc BMI, AA > white > Asian, no exercise, post surgical/chemo, h/o premenstrual symptoms Tx: low dose Paxil12.5 or Effexor 37.5 as good as higher doses, exercise, tobacco cessation, paced respiration, yoga, HRT Vitamin E, soy and Paxil interfere with tamoxifen. No: red clover, dong quai, primrose oil. Maybe: gabapentin Short-term: black cohosh, soy proteins (no long-term data) Placebo in all of these 30% Lowest dose possible for shortest period of time.

44. Herbals Ginkgo biloba: used in traditional Chinese medicine; increases blood flow by inhibiting platelet activating factor L-arginine: needed to make nitric oxide; increases blood flow Damiana: used as a sexual stimulant by Mayan people of Central America; may have progestin-like action Ginseng: used in traditional Chinese medicine; phytoestrogen activity; increases blood flow Black cohosh: phytoestrogen activity; used for menopausal symptoms Wild yam: progestin-like properties; anti-inflammatory; muscle relaxant Data from the 2002 National Health Interview Survey (n=31,044) and a 1997 random household survey (n=2055) were compared to determine the prevalence of complementary and alternative medicine (CAM) use in adults in the United States. Female gender and being an adult aged 40 to 64 years were among the greatest predictors of CAM use. The most commonly used CAM was herbal therapy, with its use increasing from 12.1% in 1997 to 18.6% in 2002. Approximately 70% of adults do not disclose CAM use to their physician. Data from the 2002 National Health Interview Survey (n=31,044) and a 1997 random household survey (n=2055) were compared to determine the prevalence of complementary and alternative medicine (CAM) use in adults in the United States. Female gender and being an adult aged 40 to 64 years were among the greatest predictors of CAM use. The most commonly used CAM was herbal therapy, with its use increasing from 12.1% in 1997 to 18.6% in 2002. Approximately 70% of adults do not disclose CAM use to their physician.

45. Commonly used oral preparations Avlimil � to enhance sexual function by increasing blood flow and relaxing body, 1 RCT to support Asotas � to increase sex drive. No data Libidol - for low sexual drive and female sexual dysfunction ArginMax � to enhance sexual function by increasing blood flow and relaxing body. 1 placebo-controlled double-blind study. Ginkgo biloba � to increase blood flow, nerve transmission, antioxidant. In open-label trial of ginkgo for antidepressant-induced sexual function, 91% of women reported positive effects(significance not reported). In placebo-controlled trial of same, no difference. Xzite - medulla oblongata, regulate mood and emotions, and increase blood flow. 1 double blind, placebo-controlled trial. Kyo-Green � barley and wheat drink. 1 open-label trial of men and women; 80% of the women reported improved sexual function after 3 months Although not peer reviewed or published, the manufacturer reports on a double-blind, placebo-controlled trial using Xzite. In this study, Xzite produced statistically significant improvement in vaginal lubrication, sexual desire, clitoral sensation, orgasmic potential, and satisfaction. In an open-label trial of men and women, 80% of the women reported improved sexual function after 3 months of Kyo-Green use. Subjects also reported increases in energy levels. Although not peer reviewed or published, the manufacturer reports on a double-blind, placebo-controlled trial using Xzite. In this study, Xzite produced statistically significant improvement in vaginal lubrication, sexual desire, clitoral sensation, orgasmic potential, and satisfaction. In an open-label trial of men and women, 80% of the women reported improved sexual function after 3 months of Kyo-Green use. Subjects also reported increases in energy levels.

46. Commonly used topicals Zestra - One published double-blind, placebo-controlled, cross-over trial Vigorelle�Ingredients include damiana leaf, sumaroot, mothewrot, wild yam, ginkgo biloba, peppermint leaf, L-arginine, and vitamins A and C Climatique�Ingredients include L-arginine, niacin, menthol, and glycerylpolymethacrylate ProSensual�Ingredients include natural mint, orange, and clove oil Alura�Ingredients include menthol and L-arginine

47. Vaginal changes Epithelial cells contain less glycogen, resulting in increased pH. Increased E coli and loss of lactobacilli leave tissue thin, friable, vulnerable to infection. Urethra and urinary tract undergo atrophic changes similar to vagina; dysuria, urgency, frequency, and suprapubic pain may often occur without infection.

48. Vaginal Atrophy Estring (17 beta estradiol): every 3 months Vagifem 25mcg (estradiol): q 14 d, then 2 x week Conjugated estrogen (Premarin): 0.3 mg 3 x week HRT At suggested doses, barely detectable serum levels. Most use less. �

49. STD screening Strong recommendation (A) for routine screening in all sexually active women, younger than 25yo, and those at increased risk for chlamydial infection. All pregnant women <25yo and older with risk No indication for screening if >25yo and no increased risk.

50. HIV screening Strong recommendation for screening in all adolescents and adults at increased risk (A) All pregnant women (A). No rec for or against routine screening in those not at risk. 9/06 CDC recommends all 13-64yo be screened with opt-out. No separate consent

51. Birth control and HIV In trial in Zambia, hormonal contraception was associated with faster rates of HIV disease progression in women off ART. Progression of HIV or to death was more likely in women on OCPs (HR, 1.7)or Depot (HR, 1.6) than IUDs. Specific contributions of estrogen and progesterone could not be evaluated in this study. Stringer EM et al. HIV disease progression by hormonal contraceptive method: Secondary analysis of a randomized trial. AIDS 2009 Jul 17; 23:1377. Does Hormonal Contraception Accelerate HIV Progression? Use of either DMPA or OCPs was associated with hastened unfavorable disease outcomes. Access to safe and effective contraception is particularly important for HIV-infected women, both for maintaining health and for preventing perinatal transmission. In a previous trial, conducted in Zambia, investigators randomized 595 HIV-infected women who were not receiving antiretroviral therapy to copper intrauterine devices or hormonal contraception (depot medroxyprogesterone acetate [DMPA] or oral contraceptive pills [OCPs]). Unexpectedly, hormonal contraception was associated with faster rates of HIV disease progression. Now, the investigators report a secondary analysis that was designed to determine whether this effect on disease progression differed by type of hormonal contraception. Among women who were allocated to hormonal contraception, 63% chose DMPA and 37% chose OCPs. Progression to the composite endpoint (death or eligibility for antiretroviral therapy) during the 24-month study period was more likely among women who were randomized to OCPs (adjusted hazard ratio, 1.7) or DMPA (AHR, 1.6) than among those randomized to IUDs. Analyses that took into account whether participants switched contraceptive methods during the study did not substantially alter the conclusions. Comment: Although these researchers did not originally postulate that HIV progression would be faster among users of hormonal contraception, this finding is consistent with previous studies in humans and primates. Unfortunately, the specific contributions of estrogen and progesterone could not be evaluated in this study. The authors note that these results are worrisome but not definitive; thus, gaining a better understanding of the interactions between HIV progression and hormonal contraception should be a top priority. Notably, 50% of women who were randomized to IUDs switched methods during the study, suggesting low satisfaction with this method, even if � or perhaps because � pregnancy was effectively prevented. This finding underscores the need for further research on decision making about contraception and pregnancy among African women.Does Hormonal Contraception Accelerate HIV Progression? Use of either DMPA or OCPs was associated with hastened unfavorable disease outcomes. Access to safe and effective contraception is particularly important for HIV-infected women, both for maintaining health and for preventing perinatal transmission. In a previous trial, conducted in Zambia, investigators randomized 595 HIV-infected women who were not receiving antiretroviral therapy to copper intrauterine devices or hormonal contraception (depot medroxyprogesterone acetate [DMPA] or oral contraceptive pills [OCPs]). Unexpectedly, hormonal contraception was associated with faster rates of HIV disease progression. Now, the investigators report a secondary analysis that was designed to determine whether this effect on disease progression differed by type of hormonal contraception. Among women who were allocated to hormonal contraception, 63% chose DMPA and 37% chose OCPs. Progression to the composite endpoint (death or eligibility for antiretroviral therapy) during the 24-month study period was more likely among women who were randomized to OCPs (adjusted hazard ratio, 1.7) or DMPA (AHR, 1.6) than among those randomized to IUDs. Analyses that took into account whether participants switched contraceptive methods during the study did not substantially alter the conclusions. Comment: Although these researchers did not originally postulate that HIV progression would be faster among users of hormonal contraception, this finding is consistent with previous studies in humans and primates. Unfortunately, the specific contributions of estrogen and progesterone could not be evaluated in this study. The authors note that these results are worrisome but not definitive; thus, gaining a better understanding of the interactions between HIV progression and hormonal contraception should be a top priority. Notably, 50% of women who were randomized to IUDs switched methods during the study, suggesting low satisfaction with this method, even if � or perhaps because � pregnancy was effectively prevented. This finding underscores the need for further research on decision making about contraception and pregnancy among African women.

52. Lesbian Health

54. Revised ACOG Guidelines Cervical cancer screening should begin at age 21 regardless of age at onset of sexual activity. Cervical cytology screening from age 21 to 29 is recommended every 2 years but should be more frequent in women who are HIV-positive, are immunosuppressed, were exposed in utero to diethylstilbestrol, or have been treated for CIN 2, 3 or cervical cancer. Women age 30 who have three consecutive negative screens and who do not fit the above criteria for more-frequent screening may be tested every 3 years. Co-testing with cervical cytology and high-risk HPV typing is also appropriate; if both tests are negative, rescreening in 3 years is warranted. ACOG Committee on Practice Bulletins � Gynecology. ACOG Practice Bulletin No. 109: Cervical cytology screening. 2009 Dec; 114:1409. 1st at age 21or sex +3yrs q3yrs. Stop age 65 with prev nl. NO in benign hysterectomy. ACS At 30yo and if 3 nl, q2-3y. At 70: if 10y, clean stop ACOG To 30: q1y, At 30:if nl, q1-3yr or q3y pap/HPV 1st at age 21or sex +3yrs q3yrs. Stop age 65 with prev nl. NO in benign hysterectomy. ACS At 30yo and if 3 nl, q2-3y. At 70: if 10y, clean stop ACOG To 30: q1y, At 30:if nl, q1-3yr or q3y pap/HPV

55. Revised ACOG Guidelines Cervical cancer screening is unnecessary in women who have undergone hysterectomies for benign disease and who have no histories of CIN. Discontinuation of screening after age 65 or 70 is reasonable in women with 3 negative consecutive tests and no cervical abnormalities during the previous decade. Women with histories of CIN 2, 3 or cancer should undergo annual screening for 20 years after treatment. HPV vaccination does not change these recommendations. ACOG Committee on Practice Bulletins � Gynecology. ACOG Practice Bulletin No. 109: Cervical cytology screening. 2009 Dec; 114:1409.

56. Cervical Cancer Screening Majority of cancers occur in women who have never been screened or have not been screened in the last 5 years. Sensitivity of a single pap for high grade lesions 60-80%. American Cancer Society (ACS) recommends annual screening with conventional paps and biennial screening with liquid based cytology until age 30 before lengthening the screening interval. ACOG lists previous HPV infection or other STDs or high risk behavior as reasons to continue annual screening.

57. Cervical Cancer Screening Cervical cytology can be obtained using either conventional or liquid based technology. Dutch study of 90,000 women showed both were comparable. Liquid based is more $$ but more accurate in the presence of inflammation or menses and reflex HPV, Gonorrhea, and Chlamydia testing can be done on the same specimen, lab processing is easier, quicker. 90% of invasive cervical cancer have HPV DNA. The majority of people with HPV DNA do not progress to invasive cervical cancer. Siebers AG et al. Comparison of liquid-based cytology with conventional cytology for detection of cervical cancer precursors: A randomized controlled trial. JAMA 2009 Oct 28; 302:1757. The results of this trial, however, are unlikely to influence practice in the U.S., where liquid-based cytology has largely replaced conventional Pap testing. Liquid-based cytology is more expensive. However, some costs can be recovered: Fewer unsatisfactory preparations occur (largely because menstrual bleeding does not interfere), laboratory processing and microscopic scanning are easier and quicker, and testing for human papillomavirus (HPV) as well as Chlamydia trachomatis and Neisseria gonorrhoeae can be performed on the remaining sample. As more women are vaccinated against HPV, approaches to � and frequency of � cervical cancer screening by any method should be reevaluated.The results of this trial, however, are unlikely to influence practice in the U.S., where liquid-based cytology has largely replaced conventional Pap testing. Liquid-based cytology is more expensive. However, some costs can be recovered: Fewer unsatisfactory preparations occur (largely because menstrual bleeding does not interfere), laboratory processing and microscopic scanning are easier and quicker, and testing for human papillomavirus (HPV) as well as Chlamydia trachomatis and Neisseria gonorrhoeae can be performed on the remaining sample. As more women are vaccinated against HPV, approaches to � and frequency of � cervical cancer screening by any method should be reevaluated.

58. HPV vaccine HPV quadrivalent vaccine (Gardasil) Also decreases incidence of genital warts Recent FDA approval for preventing genital warts in boys 90% clear in 2 years especially <30 yo Vaccine almost 100% effective in preventing diseases caused by the 4 HPV types covered by the vaccine. Indicated for women 9-26 yo. 3 shots about $120 each. Many insurances covering. Can HPV Vaccination Combat Genital Warts? Yes � and the benefit extends beyond vaccinated women to their male sexual partners. In mid-2007, Australia began a free quadrivalent human papillomavirus (HPV) vaccination program for schoolgirls and young women (age, 26); by the end of 2007, about 70% of the target population had received all three doses. Now, investigators have assessed the initial effect of such immunization on the incidence of genital warts at a large sexual health clinic in Melbourne. Overall, genital warts were diagnosed in 11% of 36,055 new patients who presented from 2004 through 2008. The proportion of young women (age, <28) with diagnoses of genital warts declined by 25% each quarter of 2008 (P<0.001). The proportion of heterosexual men diagnosed with genital warts decreased by 5% per quarter that year (P=0.031). In contrast, the proportions of older women (age, 28), and of men who have sex with men, who were diagnosed with genital warts remained stable, as did the proportion of patients who presented with genital herpes. Comment: The benefit of the HPV quadrivalent vaccine extends beyond preventing dysplasia and cervical cancer � a long-term goal � to reducing the burden of genital warts. These study findings support benefit of HPV immunization not only to vaccinated women but also to their male sexual partners, and, in turn, to partners' subsequent female partners. Because the vaccine currently is provided only to women, any protection of men against genital warts is indirect. Clinicians might want to provide these emerging data to their patients who are considering immunization. Discussion about the benefits of HPV vaccination is likely to continue, especially given that the FDA recently approved the quadrivalent vaccine (Gardasil) for preventing genital warts in boys and the bivalent vaccine (Cervarix) for preventing cervical cancer in girls. Fairley CK et al. Rapid decline in presentations of genital warts after the implementation of a national quadrivalent human papillomavirus vaccination programme for young women. Sex Transm Infect 2009 Oct 16 Can HPV Vaccination Combat Genital Warts? Yes � and the benefit extends beyond vaccinated women to their male sexual partners. In mid-2007, Australia began a free quadrivalent human papillomavirus (HPV) vaccination program for schoolgirls and young women (age, 26); by the end of 2007, about 70% of the target population had received all three doses. Now, investigators have assessed the initial effect of such immunization on the incidence of genital warts at a large sexual health clinic in Melbourne. Overall, genital warts were diagnosed in 11% of 36,055 new patients who presented from 2004 through 2008. The proportion of young women (age, <28) with diagnoses of genital warts declined by 25% each quarter of 2008 (P<0.001). The proportion of heterosexual men diagnosed with genital warts decreased by 5% per quarter that year (P=0.031). In contrast, the proportions of older women (age, 28), and of men who have sex with men, who were diagnosed with genital warts remained stable, as did the proportion of patients who presented with genital herpes. Comment: The benefit of the HPV quadrivalent vaccine extends beyond preventing dysplasia and cervical cancer � a long-term goal � to reducing the burden of genital warts. These study findings support benefit of HPV immunization not only to vaccinated women but also to their male sexual partners, and, in turn, to partners' subsequent female partners. Because the vaccine currently is provided only to women, any protection of men against genital warts is indirect. Clinicians might want to provide these emerging data to their patients who are considering immunization. Discussion about the benefits of HPV vaccination is likely to continue, especially given that the FDA recently approved the quadrivalent vaccine (Gardasil) for preventing genital warts in boys and the bivalent vaccine (Cervarix) for preventing cervical cancer in girls. Fairley CK et al. Rapid decline in presentations of genital warts after the implementation of a national quadrivalent human papillomavirus vaccination programme for young women. Sex Transm Infect 2009 Oct 16

59. HPV screening in the Third World More than three quarters of the world�s 500,000 annual cervical cancer cases occur in developing countries Study with 130,000 found that one-time HPV screening was associated with fewer cervical cancer deaths than cytologic testing or visual cervical inspection with acetic acid Sankaranarayanan R et al. HPV screening for cervical cancer in rural India. N Engl J Med 2009 Apr 2; 360:1385. In a cluster-randomized, controlled trial in rural India, researchers evaluated the effects of a single round of HPV screening on rates of advanced cervical cancer and cervical cancer deaths. More than 130,000 women (age range, 30�59) were assigned to four groups: HPV testing (13 high-risk types), cytologic testing, visual cervical inspection with acetic acid (VIA), or no screening (the current standard of care in this area of India; women in the control group received information about how to obtain screening). Women with positive screening tests underwent colposcopy and treatment as needed. At 8 years of follow-up, 34 cervical cancer deaths had occurred in the HPV-screened group and 64 cervical cancer deaths had occurred in the control group (hazard ratio, 0.52). For detection of advanced cervical cancers, HR was 0.47 in the HPV-screened group compared with the control group. Rates of advanced cervical cancer and cancer-related death also were substantially lower in the HPV-screened group than in the cytologic-screened and VIA-screened groups. Comment: In showing that a single round of HPV screening (compared with cytologic or VIA screening) had the most marked effect on preventing cervical cancer deaths, these results have tremendous international health implications: Single rounds of HPV screening are much easier to implement than repetitive cytologic screening, particularly in resource-poor countries where cervical cancer is relatively common. Nonetheless, we should not rush to apply such findings to populations with optimal resources. Clinicians in the U.S. should continue to screen as recommended by the American Society for Colposcopy and Cervical Pathology .In a cluster-randomized, controlled trial in rural India, researchers evaluated the effects of a single round of HPV screening on rates of advanced cervical cancer and cervical cancer deaths. More than 130,000 women (age range, 30�59) were assigned to four groups: HPV testing (13 high-risk types), cytologic testing, visual cervical inspection with acetic acid (VIA), or no screening (the current standard of care in this area of India; women in the control group received information about how to obtain screening). Women with positive screening tests underwent colposcopy and treatment as needed. At 8 years of follow-up, 34 cervical cancer deaths had occurred in the HPV-screened group and 64 cervical cancer deaths had occurred in the control group (hazard ratio, 0.52). For detection of advanced cervical cancers, HR was 0.47 in the HPV-screened group compared with the control group. Rates of advanced cervical cancer and cancer-related death also were substantially lower in the HPV-screened group than in the cytologic-screened and VIA-screened groups. Comment: In showing that a single round of HPV screening (compared with cytologic or VIA screening) had the most marked effect on preventing cervical cancer deaths, these results have tremendous international health implications: Single rounds of HPV screening are much easier to implement than repetitive cytologic screening, particularly in resource-poor countries where cervical cancer is relatively common. Nonetheless, we should not rush to apply such findings to populations with optimal resources. Clinicians in the U.S. should continue to screen as recommended by the American Society for Colposcopy and Cervical Pathology .

63. Breast masses Common but usually benign. CBE/imaging and tissue sampling highest yield for definitive diagnosis. Risk factor assessment key. Mammography screens for occult malignancy in the same and contralateral breast and can detect malignant lesions in older women though not as sensitive in women <40. Fine needle aspiration fast, inexpensive, and can reliably distinguish between solid and cystic masses.

64. USPSTF Guidelines 2009 Update USPSTF now recommends against routine screening of younger women (40�49 yo). Decisions about screening women younger than 50 should be individualized. Biennial mammo recommended for women 50-74 yo. Evidence is insufficient for women >75 yo. Breast Cancer Screening: Who, When, and How? New USPSTF guidelines narrow the proposed age range for screening mammography and recommend biennial screening. In 2002, the U.S. Preventive Services Task Force (USPSTF) recommended screening mammography every 1 to 2 years for all women 40 or older. In a 2009 update, the task force has revised its guidelines based on: 1) a systematic review of the benefits and harms of screening; and 2) statistical modeling to estimate outcomes associated with annual versus biennial screening that begins and ends at different ages. The USPSTF now recommends against routine screening of younger women (age range, 40�49). Decisions about screening women younger than 50 should be individualized. C recommendation (The USPSTF recommends against routinely providing the service; the grading system can be accessed on the USPSTF website.) The task force recommends biennial screening mammography for all middle-aged women (age range, 50�74). B recommendation (The USPSTF recommends the service.) However, current evidence is insufficient to assess the benefits and harms of screening mammography in older women (age, 75 [I statement]). The task force also found that current evidence is insufficient to assess the benefits and risks of clinical breast examination that is performed in addition to mammography in women age 40 (I statement), as well as to assess benefits and harms of digital mammography or magnetic resonance imaging compared with film mammography. (I statement) Teaching women to perform breast self-examination is now discouraged. D recommendation (The USPSTF recommends against the service.) Comment: Understandably, breast cancer screening generates anxiety among many women. Because these new guidelines specify that mammography be performed in fewer women � and less often � reactions among women likely will be characterized by confusion and even outrage. Several other U.S. organizations still endorse annual screening beginning at age 40. Although this discrepancy will add to the confusion, it will also enable clinicians and patients to choose the guideline that is most consistent with their preconceptions and preferences. Citation(s): U.S. Preventive Services Task Force. Screening for breast cancer: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med 2009 Nov 17; 151:716.Breast Cancer Screening: Who, When, and How? New USPSTF guidelines narrow the proposed age range for screening mammography and recommend biennial screening. In 2002, the U.S. Preventive Services Task Force (USPSTF) recommended screening mammography every 1 to 2 years for all women 40 or older. In a 2009 update, the task force has revised its guidelines based on: 1) a systematic review of the benefits and harms of screening; and 2) statistical modeling to estimate outcomes associated with annual versus biennial screening that begins and ends at different ages. The USPSTF now recommends against routine screening of younger women (age range, 40�49). Decisions about screening women younger than 50 should be individualized. C recommendation (The USPSTF recommends against routinely providing the service; the grading system can be accessed on the USPSTF website.) The task force recommends biennial screening mammography for all middle-aged women (age range, 50�74). B recommendation (The USPSTF recommends the service.) However, current evidence is insufficient to assess the benefits and harms of screening mammography in older women (age, 75 [I statement]). The task force also found that current evidence is insufficient to assess the benefits and risks of clinical breast examination that is performed in addition to mammography in women age 40 (I statement), as well as to assess benefits and harms of digital mammography or magnetic resonance imaging compared with film mammography. (I statement) Teaching women to perform breast self-examination is now discouraged. D recommendation (The USPSTF recommends against the service.) Comment: Understandably, breast cancer screening generates anxiety among many women. Because these new guidelines specify that mammography be performed in fewer women � and less often � reactions among women likely will be characterized by confusion and even outrage. Several other U.S. organizations still endorse annual screening beginning at age 40. Although this discrepancy will add to the confusion, it will also enable clinicians and patients to choose the guideline that is most consistent with their preconceptions and preferences. Citation(s): U.S. Preventive Services Task Force. Screening for breast cancer: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med 2009 Nov 17; 151:716.

65. Breast masses

67. Breast masses

69. Breast Pain Classified as cyclical mastalgia associated with menses or noncyclical mastalgia. Noncyclic is further classified as breast pain or chest wall pain. Both have chronic-relapsing course. Unknown cause Cyclical mastalgia is often bilateral and more responsive to treatment whereas noncyclical mastalgia is can be unilateral or bilateral.

70. Treatment of Breast Pain Well-fitting support bra, low-fat low-carb No evidence for evening primose oil, vit E or methykxanthine-restricted diet (avoidance of coffee, tea, chocolate, and cola) Evidence supported therapies include bromocriptine, tamoxifen, danazol (the only FDA-approved medication). Danazol increases DVT risk and is teratogenic so must be taken with nonhormonal contraception. If severe and persistent, local injection of steroid and a local anesthetic.

71. Prognosis of Breast Pain The risk of breast cancer in patients with only breast pain is 0.8-2%. Localized pain followed by detection of a lump is the presenting symptom in 18% of patients with breast cancer. Both cyclical and noncyclical mastalgia resolves spontaneously in 20-50%.

72. Breast Cancer Screening The balance of benefit and potential harms from mammography improves with increasing age between 40-70 Those most likely to benefit are those at increased risk FMHx in a mother or sister Previous biopsy with atypical hyperplasia First childbirth after age 30

73. Breast Cancer Screening � New USPSTF guidelines narrow the age range and recommend biennial screening. In 2002, USPSTF recommended screening mammography every 1 to 2 years for all women 40 or older. In a 2009 update, the task force has revised its guidelines based on: 1) a systematic review of the benefits and harms of screening; and 2) statistical modeling to estimate outcomes associated with annual versus biennial screening that begins and ends at different ages.

74. Breast Cancer Screening � New USPSTF guidelines narrow the age range and recommend biennial screening. Recommends against routine screening of younger women (40�49yo). Decisions about screening women younger than 50 should be individualized. (C recommendation) Recommends biennial screening mammography for all middle-aged women (50�74yo). (B recommendation) Evidence is insufficient to assess the benefits and harms of screening mammography in older women (>75yo). (I statement) New USPSTF guidelines narrow the proposed age range for screening mammography and recommend biennial screening. A rec B rec = The USPSTF recommends the service. C rec = The USPSTF recommends against routinely providing the service. D rec = The USPSTF recommends against the service. I statement = Insufficient evidence to assess the benefits and harmsNew USPSTF guidelines narrow the proposed age range for screening mammography and recommend biennial screening. A rec B rec = The USPSTF recommends the service. C rec = The USPSTF recommends against routinely providing the service. D rec = The USPSTF recommends against the service. I statement = Insufficient evidence to assess the benefits and harms

75. Breast Cancer Screening � New USPSTF guidelines narrow the age range and recommend biennial screening. Evidence is insufficient for clinical breast examination that is performed in addition to mammography in women age 40 (I statement) Evidence is insufficient for digital mammography or MRI compared with film mammography. (I statement) Teaching women to perform breast self-examination is now discouraged. D recommendation D rec = The USPSTF recommends against the service.D rec = The USPSTF recommends against the service.

76. Breast Cancer Screening Trials looking at improved breast cancer mortality, no difference was seen between annual and biennial mammography. However, most expert recommendations are for annual mammography due to the low sensitivity of the test

77. Breast Cancer The age to discontinue mammography is uncertain Only 2 RCT�s looked at patients > 69, and only 1 at patients >74 Older women have a higher probability of getting and dying from breast cancer, but also a greater risk of death from other causes Women with co-morbid conditions limiting their life expectancy are unlikely to benefit from screening mammography

78. Breast Tenderness after starting menopausal HT: an ominous sign? Users of HT who reported new-onset breast tenderness had 48% higher risk for breast cancer than did HT users who did not report this complaint (P=0.02). Breast tenderness has been linked to high mammographic density, an independent risk factor for breast cancer. Crandall CJ et al. New-onset breast tenderness after initiation of estrogen plus progestin therapy and breast cancer risk. Arch Intern Med 2009 Oct 12; 169:1684. Breast Tenderness After Starting Menopausal HT: An Ominous Sign? In the WHI trial, HT users with new-onset breast tenderness had higher risk for breast cancer than did HT users without this side effect. Breast tenderness is a common side effect associated with initiation of menopausal hormone therapy. In a report from the Women's Health Initiative estrogen-plus-progestin (E+P) trial, investigators assessed self-reported breast tenderness at baseline and after 12 months in relation to HT use and risk for breast cancer. Among women without breast tenderness at baseline, incidence of breast tenderness at 12 months was threefold higher in participants assigned to HT than among those assigned to placebo (36.1% vs. 11.8%; P<0.001). Women who reported new-onset breast tenderness were older and more likely to be black or Latina than were women without this complaint. More than three quarters of participants who reported new-onset breast tenderness (most often rated as mild) had been assigned to HT. Users of HT who reported new-onset breast tenderness had 48% higher risk for breast cancer than did HT users who did not report this complaint (P=0.02). In contrast, new-onset breast tenderness in women who were assigned to placebo was not associated with elevated breast cancer risk. Comment: Breast tenderness has been linked to high mammographic density, an independent risk factor for breast cancer. New-onset breast tenderness is also common among women when they begin HT and generally is dose-dependent. The results of this analysis suggest that new-onset breast tenderness predicts higher risk for breast cancer in women who use E+P HT. To put this excess risk in perspective, recall that the original E+P trial results showed that use of estrogen-progestin HT was associated with eight additional cases of breast cancer diagnosed per 10,000 women-years. The present analysis suggests that, if new-onset breast tenderness is present, absolute risk for breast cancer � although greater � is still relatively modest. Women who are considering initiating or continuing E+P HT should be counseled about its risks and benefits (as has long been recommended). Those women who experience new-onset breast tenderness upon starting E+P HT should discuss this condition with their clinicians, as it could affect decisions about HT choice, dose, and duration, as well as strategies for breast cancer surveillance. Published in Journal Watch Women's Health November 19, 2009Breast Tenderness After Starting Menopausal HT: An Ominous Sign? In the WHI trial, HT users with new-onset breast tenderness had higher risk for breast cancer than did HT users without this side effect. Breast tenderness is a common side effect associated with initiation of menopausal hormone therapy. In a report from the Women's Health Initiative estrogen-plus-progestin (E+P) trial, investigators assessed self-reported breast tenderness at baseline and after 12 months in relation to HT use and risk for breast cancer. Among women without breast tenderness at baseline, incidence of breast tenderness at 12 months was threefold higher in participants assigned to HT than among those assigned to placebo (36.1% vs. 11.8%; P<0.001). Women who reported new-onset breast tenderness were older and more likely to be black or Latina than were women without this complaint. More than three quarters of participants who reported new-onset breast tenderness (most often rated as mild) had been assigned to HT. Users of HT who reported new-onset breast tenderness had 48% higher risk for breast cancer than did HT users who did not report this complaint (P=0.02). In contrast, new-onset breast tenderness in women who were assigned to placebo was not associated with elevated breast cancer risk. Comment: Breast tenderness has been linked to high mammographic density, an independent risk factor for breast cancer. New-onset breast tenderness is also common among women when they begin HT and generally is dose-dependent. The results of this analysis suggest that new-onset breast tenderness predicts higher risk for breast cancer in women who use E+P HT. To put this excess risk in perspective, recall that the original E+P trial results showed that use of estrogen-progestin HT was associated with eight additional cases of breast cancer diagnosed per 10,000 women-years. The present analysis suggests that, if new-onset breast tenderness is present, absolute risk for breast cancer � although greater � is still relatively modest. Women who are considering initiating or continuing E+P HT should be counseled about its risks and benefits (as has long been recommended). Those women who experience new-onset breast tenderness upon starting E+P HT should discuss this condition with their clinicians, as it could affect decisions about HT choice, dose, and duration, as well as strategies for breast cancer surveillance. Published in Journal Watch Women's Health November 19, 2009

79. Breast Cancer Genetic Testing Lifetime breast cancer risk of 50-85% in women with BRCA1 and BRCA2 mutations. Routine mammography detects approx. 50% of tumors in women with the mutations vs. 75% of tumors in women w/o mutation. On the basis of biopsy rates, sensitivity and specificity for the detection of breast cancer were 77%/95.4 % for MRI, 36% /99.8% for mammo, and 9.1% and 99.3% for CBE. MRI more sensitive than sono, mammo, or CBE in BRCA carriers.

80. BRCA Testing No: Routine (D) Yes:Family hx (B) 2 1st degree rel w/breast cancer,1dx <50 OR 3 1st/2nd degree rel w/breast cancer OR 1 1st/2nd degree rel w/breast/ovarian cancer How do you screen for BRCA1 and BRCA2?

81. BRCA Testing Testing only those index cases who were of Ashkenazi Jewish ancestry, had personal histories of breast cancer, or had family histories of breast or ovarian cancer (Society of Gynecologic Oncologists [SGO] recommendation) Cost-effective approach to lowering future breast/ovarian CA ($20-32K per QALY) Kwon JS et al. Preventing future cancer by testing women with ovarian cancer for BRCA mutations. J Clin Oncol 2009 Oct 19 BRCA Testing of Women with Ovarian Cancer: Which Strategy Is Best? Testing women of Ashkenazi Jewish ancestry or with family histories of breast or ovarian cancer was projected to be cost-effective for lowering subsequent cancer rates among first-degree relatives. About 10% of women with ovarian cancer carry BRCA mutations. Investigators developed a simulation model to estimate costs and benefits of BRCA testing in women with ovarian cancer (index cases) using one of four strategies: 1. No BRCA testing (reference strategy) 2. Testing only those index cases who were of Ashkenazi Jewish ancestry, had personal histories of breast cancer, or had family histories of breast or ovarian cancer (Society of Gynecologic Oncologists [SGO] recommendation) 3. Testing only if index cancer was serous (the most common form of ovarian cancer) 4. Testing all index cases The model was based on the assumption that, if index cases tested positive, first-degree relatives (FDRs) could be tested and, if positive, could undergo prophylactic procedures. Projections were made for two scenarios: the "ideal," in which all FDRs of mutation-positive index cases were tested and all who were positive underwent prophylactic surgery; and the "realistic," in which 50% of FDRs of mutation-positive cases were tested and 70% who were positive underwent prophylactic surgery. In the ideal scenario, strategies 2 (i.e., SGO-based), 3, and 4 were associated with approximate costs of US$20,000, $65,000, and $74,000 per life-year gained, respectively, compared with no testing. In the realistic scenario, strategies 2, 3, and 4 were associated with approximate costs of $32,000, $128,000, and $148,000 per life-year gained, respectively, compared with no testing. The authors concluded that testing ovarian cancer cases according to the SGO strategy represents a cost-effective approach to lowering rates of future breast and ovarian cancers among FDRs and that more-inclusive testing approaches could prevent more cases (albeit at substantially higher costs). Comment: More women are learning about familial breast and ovarian cancer and the availability of BRCA testing. When a woman without a history of cancer informs her clinician about a first-degree relative who has ovarian or breast cancer, BRCA testing, if appropriate, optimally is performed in the affected relative. If the test is positive, unaffected relatives can be counseled and tested. Unfortunately, when I suggest this strategy to my patients, more often than not the affected relative does not undergo BRCA testing. This might reflect challenges such as testing costs, reluctance to be tested, and limited access to clinicians who are willing to counsel and test. By highlighting the possible benefits and costs associated with BRCA testing, reports such as this one should lead to more candidates being tested appropriately. Published in Journal Watch Women's Health November 19, 2009 BRCA Testing of Women with Ovarian Cancer: Which Strategy Is Best? Testing women of Ashkenazi Jewish ancestry or with family histories of breast or ovarian cancer was projected to be cost-effective for lowering subsequent cancer rates among first-degree relatives. About 10% of women with ovarian cancer carry BRCA mutations. Investigators developed a simulation model to estimate costs and benefits of BRCA testing in women with ovarian cancer (index cases) using one of four strategies: 1. No BRCA testing (reference strategy) 2. Testing only those index cases who were of Ashkenazi Jewish ancestry, had personal histories of breast cancer, or had family histories of breast or ovarian cancer (Society of Gynecologic Oncologists [SGO] recommendation) 3. Testing only if index cancer was serous (the most common form of ovarian cancer) 4. Testing all index cases The model was based on the assumption that, if index cases tested positive, first-degree relatives (FDRs) could be tested and, if positive, could undergo prophylactic procedures. Projections were made for two scenarios: the "ideal," in which all FDRs of mutation-positive index cases were tested and all who were positive underwent prophylactic surgery; and the "realistic," in which 50% of FDRs of mutation-positive cases were tested and 70% who were positive underwent prophylactic surgery. In the ideal scenario, strategies 2 (i.e., SGO-based), 3, and 4 were associated with approximate costs of US$20,000, $65,000, and $74,000 per life-year gained, respectively, compared with no testing. In the realistic scenario, strategies 2, 3, and 4 were associated with approximate costs of $32,000, $128,000, and $148,000 per life-year gained, respectively, compared with no testing. The authors concluded that testing ovarian cancer cases according to the SGO strategy represents a cost-effective approach to lowering rates of future breast and ovarian cancers among FDRs and that more-inclusive testing approaches could prevent more cases (albeit at substantially higher costs). Comment: More women are learning about familial breast and ovarian cancer and the availability of BRCA testing. When a woman without a history of cancer informs her clinician about a first-degree relative who has ovarian or breast cancer, BRCA testing, if appropriate, optimally is performed in the affected relative. If the test is positive, unaffected relatives can be counseled and tested. Unfortunately, when I suggest this strategy to my patients, more often than not the affected relative does not undergo BRCA testing. This might reflect challenges such as testing costs, reluctance to be tested, and limited access to clinicians who are willing to counsel and test. By highlighting the possible benefits and costs associated with BRCA testing, reports such as this one should lead to more candidates being tested appropriately. Published in Journal Watch Women's Health November 19, 2009

82. QALY Measure of disease burden, including both the quality and the quantity of life lived Each year in perfect health =1.0 and death =0.0. If loss of limb, blind, paralyzed, etc, the extra life-years are given a value between 0 and 1. Used to allocate healthcare resources Controversial The QALY is used in cost-utility analysis to calculate the ratio of cost to QALYs saved for a particular health care intervention. This is then used to allocate healthcare resources, with an intervention with a lower cost to QALY saved ratio being preferred over an intervention with a higher ratio. This method is controversial because it means that some people will not receive treatment as it is calculated that cost of the intervention is not warranted by the benefit to their quality of life. However, its supporters argue that since health care resources are inevitably limited, this method enables them to be allocated in the way that is most beneficial to society instead of most beneficial to the patient. The meaning and usefulness of the QALY is debated. Perfect health is hard, if not impossible, to define. Some argue that there are health states worse than death, and that therefore there should be negative values possible on the health spectrum (indeed, some health economists have incorporated negative values into calculations). Determining the level of health depends on measures that some argue place disproportionate importance on physical pain or disability over mental health. The effects of a patient's health on the quality of life of others (e.g. caregivers or family) do not figure into these calculations.The QALY is used in cost-utility analysis to calculate the ratio of cost to QALYs saved for a particular health care intervention. This is then used to allocate healthcare resources, with an intervention with a lower cost to QALY saved ratio being preferred over an intervention with a higher ratio. This method is controversial because it means that some people will not receive treatment as it is calculated that cost of the intervention is not warranted by the benefit to their quality of life. However, its supporters argue that since health care resources are inevitably limited, this method enables them to be allocated in the way that is most beneficial to society instead of most beneficial to the patient. The meaning and usefulness of the QALY is debated. Perfect health is hard, if not impossible, to define. Some argue that there are health states worse than death, and that therefore there should be negative values possible on the health spectrum (indeed, some health economists have incorporated negative values into calculations). Determining the level of health depends on measures that some argue place disproportionate importance on physical pain or disability over mental health. The effects of a patient's health on the quality of life of others (e.g. caregivers or family) do not figure into these calculations.

83. Breast cancer prevention Consumption of dried or fresh mushrooms was associated with lower breast cancer risk in Chinese women, especially when they also drank green tea. Mushrooms and their extracts, as well as polyphenols in green tea, seem to be anticarcinogenic for breast cancer. Zhang M et al. Dietary intakes of mushrooms and green tea combine to reduce the risk of breast cancer in Chinese women. Int J Cancer 2009 Mar 15; 124:1404 Participants completed one-time questionnaires that assessed their intake of foods, including fresh and dried mushrooms and green tea. Women who had breast cancer were less educated, less likely to have used oral contraceptives or hormone therapy, and more likely to have passive smoke exposure or first-degree relatives with breast cancer than control women. Adjusted analyses showed that both premenopausal and postmenopausal women in the top quartiles of fresh or dried mushroom consumption had the lowest risk for breast cancer: Compared with women who ate no mushrooms, those who consumed 10 g of fresh mushrooms daily had an adjusted odds ratio (AOR) of 0.34 for breast cancer, and those who ate 4 g of dried mushrooms daily had an AOR of 0.50. The effect of mushroom consumption on breast cancer risk was dose dependent. Moreover, intake of fresh or dried mushrooms plus green tea had additive, dose-dependent effects on breast cancer risk. AOR was 0.11 for women who consumed the most green tea plus fresh mushrooms and was 0.18 for those who consumed the most green tea plus dried mushrooms.Participants completed one-time questionnaires that assessed their intake of foods, including fresh and dried mushrooms and green tea. Women who had breast cancer were less educated, less likely to have used oral contraceptives or hormone therapy, and more likely to have passive smoke exposure or first-degree relatives with breast cancer than control women. Adjusted analyses showed that both premenopausal and postmenopausal women in the top quartiles of fresh or dried mushroom consumption had the lowest risk for breast cancer: Compared with women who ate no mushrooms, those who consumed 10 g of fresh mushrooms daily had an adjusted odds ratio (AOR) of 0.34 for breast cancer, and those who ate 4 g of dried mushrooms daily had an AOR of 0.50. The effect of mushroom consumption on breast cancer risk was dose dependent. Moreover, intake of fresh or dried mushrooms plus green tea had additive, dose-dependent effects on breast cancer risk. AOR was 0.11 for women who consumed the most green tea plus fresh mushrooms and was 0.18 for those who consumed the most green tea plus dried mushrooms.

84. Ovarian Cancer Screening Recommends against (D) routine screening for ovarian cancer. Includes: CA-125, Ultrasound, Pelvic Exam No evidence showing that these interventions reduce ovarian cancer mortality 6/07: Bloating/abd pain/early satiety/urinary sx everyday for 2-3 weeks: u/s and ca-125(ACS)

85. Osteoporosis Recommends women 65 and older be screened routinely for osteoporosis. Screening should begin at age 60 for women at increased risk (B). Weight < 70kg is single best predictor for presence of osteoporosis Dual energy x-ray absorptiometry (DEXA) at the femoral neck is the best predictor of hip fracture

86. Osteoporosis NOF and AACE: > 65 or menopause with 1 risk factor What is risk ? No studies have evaluated the optimal interval for repeat screening. No data to determine age to stop screening and very little data on the treatment of osteoporosis after age 85

87. Fewer Falls with Vitamin D Every yr 1 in 3 pts >65yo have at least 1 fall. High dose vit D (700-1000 IU qd) was associated with 19% lower fall risk. Subgroup analysis showed this was independent of calcium supplementation. Bischoff-Ferrari HA et al. Fall prevention with supplemental and active forms of vitamin D: A meta-analysis of randomised controlled trials. BMJ 2009 Oct 1; 339 Fewer Falls with Vitamin D High-dose vitamin D lowered risk for falls in older individuals. Every year, one in three older adults (age, 65) experiences at least one fall, which makes fall prevention an important public health issue. Researchers performed a meta-analysis of eight double-blind randomized controlled trials to evaluate the effect of oral vitamin D supplementation on risk for falls in 2624 older adults (81% women). High-dose vitamin D (700�1000 IU daily) was associated with 19% lower fall risk (number needed to treat, 11 people for 2�36 months). Low-dose vitamin D (200�600 IU daily) did not attenuate risk significantly. Serum 25-hydroxyvitamin D3 (25[OH]D) levels of 60 nmol/L lowered fall risk by 23%, whereas concentrations <60 nmol/L had no significant effect. Subgroup analysis suggested that the effect of vitamin D was independent of calcium supplementation. Comment: These results confirm those of a 2004 meta-analysis that showed that vitamin D supplementation lowered fall risk by 22% (JW Gen Med May 7 2004) and emphasize the importance of daily high-dose vitamin D. Clinicians routinely recommend calcium supplementation for osteoporosis prevention, but they might not recommend high-dose vitamin D supplementation. Because fall prevention is crucial to averting hip fractures, clinicians should recommend 700�1000 IU of supplemental vitamin D daily to maintain patients' serum 25(OH)D concentrations at 60 nmol/L, especially in women who are older than 65. Bischoff-Ferrari HA et al. Fall prevention with supplemental and active forms of vitamin D: A meta-analysis of randomised controlled trials. BMJ 2009 Oct 1; 339 Fewer Falls with Vitamin D High-dose vitamin D lowered risk for falls in older individuals. Every year, one in three older adults (age, 65) experiences at least one fall, which makes fall prevention an important public health issue. Researchers performed a meta-analysis of eight double-blind randomized controlled trials to evaluate the effect of oral vitamin D supplementation on risk for falls in 2624 older adults (81% women). High-dose vitamin D (700�1000 IU daily) was associated with 19% lower fall risk (number needed to treat, 11 people for 2�36 months). Low-dose vitamin D (200�600 IU daily) did not attenuate risk significantly. Serum 25-hydroxyvitamin D3 (25[OH]D) levels of 60 nmol/L lowered fall risk by 23%, whereas concentrations <60 nmol/L had no significant effect. Subgroup analysis suggested that the effect of vitamin D was independent of calcium supplementation. Comment: These results confirm those of a 2004 meta-analysis that showed that vitamin D supplementation lowered fall risk by 22% (JW Gen Med May 7 2004) and emphasize the importance of daily high-dose vitamin D. Clinicians routinely recommend calcium supplementation for osteoporosis prevention, but they might not recommend high-dose vitamin D supplementation. Because fall prevention is crucial to averting hip fractures, clinicians should recommend 700�1000 IU of supplemental vitamin D daily to maintain patients' serum 25(OH)D concentrations at 60 nmol/L, especially in women who are older than 65. Bischoff-Ferrari HA et al. Fall prevention with supplemental and active forms of vitamin D: A meta-analysis of randomised controlled trials. BMJ 2009 Oct 1; 339

88. Other Topics Thyroid disease PCOS Domestic Violence Common medical problems in pregnancy.

89. QUESTIONS?????? JAMA 2006: Effects of tamoxifen vs raloxifen on the risk of developing invasive breast cancer and other disease outcomes: the NSABP study of tamoxifen and raloxifen (STAR) P-2 trial. --raloxifene just as good at preventing breast cancer with less dvt/pe than tamoxifen. --risk reduction absolute is 1.2 cases of invasive breast cancer /1000 women treated for one year. NEJM 2006: Calcium plus vitamin D supplementation and the risk of fractures. More WHI.f/u 7 years. Bone density slightly higher 1.06% but no change hip fracture. Increased risk of kidney stones. --baseline women took a lot of calcium. --compare no calcium at all vs. any calcium, sig diff in hip fracture (HR 0.7; CI .51 - .98) � JAMA 2006: aspirin for the primary prevention of cardiovascular events in women and men: a sex specific meta-analysis of randomized controlled trials. --ASA reduced the risk of ischemic stroke in women and MI in men. --rec possibly all women over 65 JAMA 2004: MRI was more sensitive than ultrasound, mammography, or CBE for detecting breast cancer in BRCA1 and BRCA2 Mutation carriers. NEJM 2004: Exemestane Therapy after 2 to 3 years of Tamoxifen therapy improved survival compared with 5 years of tamoxifen therapy alone. (new guidelines now state that optimal adjuvant hormonal therapy for a postmenopausal woman with breast cancer includes an aromatase inhibitor as initial therapy or after tx with tamoxifen). JAMA JAMA 2006: Effects of CEE on breast cancer and mammography screening in postmenopausal women with hysterectomy. WHI: -- no diff in breast cancer risk in women on CEE without uterus but the cancer was more invasive in the CEE group with more bx. 7.1years � JAMA 2006: Nonhormonal therapies for menopausal hot flashes: systemic review and meta-analysis. --YES: SSRI, clonidine (0.1mg qd) and gabapentin (300 tid minimum) (SSRI: paroxetine, paroxetine CR, venlafaxine, fluoxetine, citalopram) --NO: all the rest (red clover, soy, black cohosh) � ACIP Aug 2006: HPV vaccine information --ages11-12 up to 26 ideally prior to sex activity. 0,2,6 m � JAMA 2006: Salpingooophorectomy and the risk of ovarian, fallopian tube, and peritoneal cancers in women with BRCA1 or BRCA2 mutation. --dec risk ovarian and fallopian tube cancer (adj risk in cancer was 80%) --USPSTF : rec genetic testing if (about 2%) --family BRCA+ --Ashkenazi Jew with 1 first degree or 2 second degree rel on the same side with breast/ovarian cancer --1 first degree relative with bilateral breast cancer --2 first degree relatives with breast cancer � 1 prior to 50 y/o --3 first/second degree relatives with breast cancer --2 first/second degree relatives with ovarian cancer --1 male relative with breast cancer --ASCO --1 first/second degree relative with ovarian cancer or self --1 first degree relative with breast cancer prior to 50 --2 first/second degree relatives with breast cancerJAMA 2006: Effects of tamoxifen vs raloxifen on the risk of developing invasive breast cancer and other disease outcomes: the NSABP study of tamoxifen and raloxifen (STAR) P-2 trial. --raloxifene just as good at preventing breast cancer with less dvt/pe than tamoxifen. --risk reduction absolute is 1.2 cases of invasive breast cancer /1000 women treated for one year. NEJM 2006: Calcium plus vitamin D supplementation and the risk of fractures. More WHI.f/u 7 years. Bone density slightly higher 1.06% but no change hip fracture. Increased risk of kidney stones. --baseline women took a lot of calcium. --compare no calcium at all vs. any calcium, sig diff in hip fracture (HR 0.7; CI .51 - .98) � JAMA 2006: aspirin for the primary prevention of cardiovascular events in women and men: a sex specific meta-analysis of randomized controlled trials. --ASA reduced the risk of ischemic stroke in women and MI in men. --rec possibly all women over 65 JAMA 2004: MRI was more sensitive than ultrasound, mammography, or CBE for detecting breast cancer in BRCA1 and BRCA2 Mutation carriers. NEJM 2004: Exemestane Therapy after 2 to 3 years of Tamoxifen therapy improved survival compared with 5 years of tamoxifen therapy alone. (new guidelines now state that optimal adjuvant hormonal therapy for a postmenopausal woman with breast cancer includes an aromatase inhibitor as initial therapy or after tx with tamoxifen). JAMA JAMA 2006: Effects of CEE on breast cancer and mammography screening in postmenopausal women with hysterectomy. WHI: -- no diff in breast cancer risk in women on CEE without uterus but the cancer was more invasive in the CEE group with more bx. 7.1years � JAMA 2006: Nonhormonal therapies for menopausal hot flashes: systemic review and meta-analysis. --YES: SSRI, clonidine (0.1mg qd) and gabapentin (300 tid minimum) (SSRI: paroxetine, paroxetine CR, venlafaxine, fluoxetine, citalopram) --NO: all the rest (red clover, soy, black cohosh) � ACIP Aug 2006: HPV vaccine information --ages11-12 up to 26 ideally prior to sex activity. 0,2,6 m � JAMA 2006: Salpingooophorectomy and the risk of ovarian, fallopian tube, and peritoneal cancers in women with BRCA1 or BRCA2 mutation. --dec risk ovarian and fallopian tube cancer (adj risk in cancer was 80%) --USPSTF : rec genetic testing if (about 2%) --family BRCA+ --Ashkenazi Jew with 1 first degree or 2 second degree rel on the same side with breast/ovarian cancer --1 first degree relative with bilateral breast cancer --2 first degree relatives with breast cancer � 1 prior to 50 y/o --3 first/second degree relatives with breast cancer --2 first/second degree relatives with ovarian cancer --1 male relative with breast cancer --ASCO --1 first/second degree relative with ovarian cancer or self --1 first degree relative with breast cancer prior to 50 --2 first/second degree relatives with breast cancer