Occurs secondary to a genetically programmed loss of ovarian follicles .Defined as the cessation of menstrual period

1. occurs secondary to a genetically programmed loss of ovarian follicles .Defined as the cessation of menstrual periods, menopause occurs at a mean age of 51.4 years in normal women

2. �The menopausal transition variation in menstrual cycle length (>7 days different from normal menstrual cycle length, which is 21 to 35 days) =2 skipped cycles and an interval of amenorrhea =60 days elevated serum FSH concentration Cessation menstrual period (not recognized until after 12 months of amenorrhea).

3. Perimenopause���"around the menopause," and begins with the menopausal transition and ends 12 months after the last menstrual period Menopause���Menopause is defined by 12 months of amenorrhea after the final menstrual period. It reflects complete, or near complete, ovarian follicular depletion and absence of ovarian estrogen secretion. Postmenopause���is defined as (early) the first five years after the final menstrual period. It is characterized by further and complete dampening of ovarian function and accelerated bone loss; many women in this stage continue to have hot flashes. (late) begins five years after the final menstrual period and ends with death

4. EPIDEMIOLOGY� Although the average age at menopause is approximately 51 years, for 5 percent of women, it occurs after age 55 (late menopause), and for another 5 percent, between ages 40 to 45 years (early menopause). Menopause occurring prior to age 40 years is considered to be premature ovarian failure

5. The age of menopause is reduced by about two years in women who smoke . There is also a tendency for women who have never had children and for those with more regular cycles to have an earlier age of menopause Other factors that may be important include: A family history of early menopause A history of type 1 diabetes mellitus The presence of a variant of form galactose-1-phosphate uridyl transferase Shorter cycle length during adolescence (which is also a predictor of higher basal FSH).

6. Menstrual cycle and hormone patterns begin to change many years prior to menopause. In the late reproductive years, prior to the menopausal transition, menstrual cycles are ovulatory, but follicular phase length begins to shorten. In the early menopausal transition, women begin to experience some menstrual irregularity. During this stage, inhibin B concentrations fall due to a decline in follicular number, and as a result, serum FSH levels begin to rise, with relative preservation of estradiol secretion (normal or high estradiol levels), but with low luteal phase progesterone concentrations .

7. The preservation of estradiol secretion appears to be due to an increase in aromatase activity. In the late menopausal transition, cycle variability increases. High FSH and low estradiol values may be suggestive of menopause, After menopause, when ovarian follicles are depleted, the ovary no longer secretes estradiol. However, it continues to produce and secrete androgens under the continued stimulation of LH

8. CLINICAL MANIFESTATIONS Bleeding patterns Chronic anovulation and Progesterone deficiency in this transition period may lead to long periods of unopposed estrogen exposure and therefore anovulatory bleeding and endometrial hyperplasia. Oligomenorrhea (irregular cycles) for six or more months, or an episode of heavy dysfunctional bleeding. Irregular or heavy bleeding during the menopausal transition may be treated with low-dose oral contraceptives or intermittent progestin therapy.

9. Hot flashes �The most common acute change during menopause is the hot flash, which occurs in up to 75 percent of women in some cultures, but only about 20 percent of these women seek medical attention for treatment of their flashes. As noted above, hot flashes are most common in the late menopausal transition and early postmenopausal periods They are self-limited, usually resolving without treatment within one to five years, although some women will continue to have hot flashes until after age 70. The prevalence of vasomotor symptoms is quite variable across cultures

10. Hot flashes typically begin as the sudden sensation of heat centered on the upper chest and face that rapidly becomes generalized. The sensation of heat lasts from two to four minutes, is often associated with profuse perspiration and occasionally palpitations, and is often followed by chills and shivering, and sometimes a feeling of anxiety. Hot flashes usually occur several times per day, although the range may be from only one or two each day to as many as one per hour during the day and night. Hot flashes are particularly common at night.

11. Sleep disturbance �A distressing feature of hot flashes is that they are often associated with arousal from sleep. In addition, primary sleep disorders are common in this population, even in the absence of hot flashes.

12. Genitourinary symptoms � The epithelial lining of the vagina and urethra are very sensitive to estrogen, and estrogen deficiency leads to thinning of the vaginal epithelium. This results in vaginal atrophy (atrophic vaginitis) causing symptoms of vaginal dryness, itching and often, dyspareunia. The prevalence of vaginal dryness was about 47 percent of women On exam, the vagina typically appears pale, with lack of the normal rugae and often has visible blood vessels or petechial hemorrhages. Vaginal pH, which is usually <4.5 in the reproductive years, increases to the 6.0 to 7.5 range in postmenopausal women not taking estrogen. The increase in pH and vaginal atrophy may lead to impaired protection against vaginal and urinary tract infection

13. Sexual dysfunction �Estrogen deficiency leads to a decrease in blood flow to the vagina and vulva. This decrease is a major cause of decreased vaginal lubrication and sexual dysfunction in menopausal women This neuropathy appears to be completely reversible with estrogen replacement therapy The cervix also can atrophy and become flush with the top of the vaginal vault. The elasticity of the vaginal wall may decrease and the entire vagina can become shorter or narrower.

14. urinary symptoms Low estrogen production after the menopause results in atrophy of the superficial and intermediate layers of the urethral epithelium with subsequent atrophic urethritis, diminished urethral mucosal seal, loss of compliance, and irritation; these changes predispose to both stress and urge urinary incontinence. The prevalence of incontinence increases with age. It has not been established, however, that the frequency of urinary incontinence increases across the menopausal transition Although data are conflicting, systemic estrogen therapy does not appear to be effective for the treatment of urinary incontinence. Recurrent urinary tract infections are also a problem for many postmenopausal women. In addition to epithelial atrophy, estrogen deficiency can increase vaginal pH and alter the vaginal flora, changes which may predispose to urinary tract infection

15. Depression� and mood changes However, a significant association between the menopausal transition and risk for depression seems apparent overall. In the largest prospective cohort study to date, the Study of Women's Health Across the Nation (SWAN) reported that women in early perimenopause had a higher rate of mood symptoms (14.9 to 18.4 percent) than premenopausal women (8 to 12 percent) These mood symptoms primarily were irritability, nervousness, and frequent mood changes, but not feeling "blue," and were more common in women with lower educational attainment.

16. Several studies have reported that a prior history of depression or PMS is a strong predictor of depressive recurrence during the menopausal transition .

17. Breast pain Breast pain and tenderness are common in the early menopausal transition, but begin to diminish in the late menopausal transition Menstrual migraines���Menstrual migraines are migraine headaches that cluster around the onset of each menstrual period. In many women, these headaches worsen in frequency and intensity during the menopausal transition . Skin changes���The collagen content of the skin and bones is reduced by estrogen deficiency. Decreased cutaneous collagen may lead to increased aging and wrinkling of the skin. The collagen changes may be minimized with estrogen.

18. Joint pain���Although the prevalence is not known, some women experience diffuse joint pain during the menopausal transition and postmenopausal period Balance���Impaired balance in postmenopausal women may be a central effect of estrogen deficiency .Problems with balance may play a major role in the incidence of forearm fractures in women. The incidence of Colles' fractures increases markedly in women at age 50 but remains stable in men up to the age of 80. A mechanism other than osteoporosis must be invoked to explain this observation because osteoporosis occurs gradually. The fracture is usually caused by falling on an outstretched hand. The role of estrogen therapy on falls is discussed elsewhere.

19. Long-term issues Bone loss���Bone loss begins prior to menopause. The annual rates of loss during these phases were approximately 1.8 to 2.3 percent in the spine and 1.0 to 1.4 percent in the hip. Higher body mass index was associated with slower bone loss; ethnicity had no effect. Cardiovascular disease Dementia�

20. DIAGNOSIS  Menopause is defined clinically as 12 months of amenorrhea in a woman over age 45 in the absence of other biological or physiological causes. The best approach to diagnosing the menopausal transition is a longitudinal assessment of menstrual cycle history and menopausal symptoms (vasomotor flushes, mood changes, sleep disturbances). Differential diagnosis���Hyperthyroidism should always be considered in the differential diagnosis pregnancy, hyperprolactinemia. Atypical hot flashes and night sweats may be due to other disorders, such as medications, carcinoid, pheochromocytoma, or underlying malignancy.

21. Hormon Replacement Therapy

22. Postmenopausal hormone therapy is currently recommended short-term for the management of moderate to severe vasomotor flushes. Long-term use for prevention of disease is no longer recommended

23. Hormone preparations� Combined, continuous conjugated estrogens e.g. (0.625 mg) and medroxyprogesteroneacetate (MPA 2.5 mg). Un-opposed estrogens (in hysterectomised patients ) Oral preparations , local , injectables , vaginal preparations and implants

24. Treat short term menopausal symptoms Disease prevention �  Uses

25. Disease prevention Coronary heart disease� Osteoporosis Dementia

26. SUMMARY AND RECOMMENDATIONS Most postmenopausal women, with the EXCEPTIONof women with breast cancer or known cardiovascular disease, who have symptoms of vaginal atrophy and/or vasomotor instability are good candidates for estrogen therapy (for the shortest duration possible depending upon symptoms). Vasomotor instability For postmenopausal women with moderate-to-severe vasomotor symptoms (and no history of breast cancer or cardiovascular disease), short-term estrogen therapy as the treatment of choice Urogenital atrophy���With the exception of women with breast cancer, almost all postmenopausal women are candidates for vaginal estrogen. Osteoporosis���We currently do not consider estrogen to be a first-line therapy for osteoporosis. Therefore, the management of women who choose not to or cannot take estrogen is the same as for other postmenopausal women. Cardiovascular disease prevention���Estrogen is NO longer indicated for the prevention of CHD in postmenopausal women. The best means of primary and secondary prevention of cardiovascular disease involves attention to risk factors such as smoking, hypertension, dyslipidemia, and diabetes mellitus.

27. WOMEN WITH POF In healthy women with premature ovarian failure, we continue their hormone therapy until their late 40s or age 50 years. At that point, the same discussion of potential risks and benefits of postmenopausal hormone therapy should take place

28. Although women with breast cancer often experience early menopause due to adjuvant chemotherapy, and may have vasomotor symptoms due to tamoxifen therapy, estrogen therapy should NOT be prescribed. The epidemiologic data and clinical trial data have been inconsistent, but the increased risk of breast cancer recurrence with estrogen therapy in one trial (HABITS), is of great concern. We therefore do not recommend estrogen for women with a personal history of breast cancer.

29. ANDROGEN REPLACEMENT � The known decrease in ovarian androgen production rates and serum androgen concentrations has caused concern that menopause might be associated with a decline in libido. An age-associated decline in sexual desire has been observed in both men and women. However, it is unclear whether the decline in libido in women is age- or menopause-related, since studies in women have not shown a significant correlation between libido and the serum estradiol or testosterone concentration

30. HRT CONTRA INDICATIONS