amenorrhea

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Amenorrhea. PrimaryAbsence of menses by age 16 with normal secondary sexual characteristicsAbsence of menses by age 14 without secondary sexual developmentSecondaryAbsence of menses for 6 months in a previously menstruating female. Events of Puberty. Thelarche (breast development)Requires estrogenPubarche/adrenarche (pubic hair development)Requires androgensMenarcheRequires:GnRH from the hypothalamusFSH and LH from the pituitaryEstrogen and progesterone from the ovariesNormal outf9459

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1: Amenorrhea Jean Amoura, MD, MSc

2: Amenorrhea Primary Absence of menses by age 16 with normal secondary sexual characteristics Absence of menses by age 14 without secondary sexual development Secondary Absence of menses for 6 months in a previously menstruating female There is a 5% lifetime incidence for some form of amenorrhea. Physiologic causes of amenorrhea are: Prepubertal status, pregnancy, lactation, and menopauseThere is a 5% lifetime incidence for some form of amenorrhea. Physiologic causes of amenorrhea are: Prepubertal status, pregnancy, lactation, and menopause

3: Events of Puberty Thelarche (breast development) Requires estrogen Pubarche/adrenarche (pubic hair development) Requires androgens Menarche Requires: GnRH from the hypothalamus FSH and LH from the pituitary Estrogen and progesterone from the ovaries Normal outflow tract

4: Are there secondary sexual characteristics?

5: Primary Amenorrhea Is there normal development of secondary sexual characteristcs? NO Think hypogonadism or hypogonadotropism

6: Amenorrhea with Immature Secondary Characteristics

7: Primary Amenorrhea Hypogonadism 30% have genetic abnormality Gonadal dysgenesis, Turner’s syndrome, mosaicism Enzyme deficiencies Kallmann’s syndrome, CNS tumors Irradiation Chemotherapy Galactosemia

8: Primary Amenorrhea with Immature Sexual Characteristics Hypogonadism (gonadal failure) Gonadal dysgenesis Irradiation Chemotherapy Galactosemia Note: gonadotropins (FSH/LH) will be high, similar to menopause Irradiation risk at >250 rads Kallmann’s = insufficient pulsatile GnRH Irradiation risk at >250 rads Kallmann’s = insufficient pulsatile GnRH

9: Gonadal Dysgenesis Chromosomally abnormal - Classic turner’s syndrome (45XO) - Turner variants (45XO/46XX),(46X-abnormal X) - Mixed gonadal dygenesis (45XO/46XY) Chromosomally normal - 46XX (Pure gonadal dysgeneis) - 46XY (Swyer’s syndrome)

10: Primary Amenorrhea with Immature Sexual Characteristics Hypogonadotropism Hypothalamic dysfunction Kallmann syndrome Anorexia nervosa Space-occupying lesion of CNS Marijuana use Pituitary damage (surgery/radiation) Constitutional delay Constitutional delay: diagnosis of exclusion after negative workup including head CT/MRI. Bone age should be delayed as well.Constitutional delay: diagnosis of exclusion after negative workup including head CT/MRI. Bone age should be delayed as well.

11: Are there secondary sexual characteristics?

12: Primary Amenorrhea Is there normal development of secondary sexual characteristics? YES Think Pregnancy Mullerian anomaly Androgen insensitivity With androgen insensitivity, there will typically be more breast development than pubic hair development.With androgen insensitivity, there will typically be more breast development than pubic hair development.

13: Primary Amenorrhea with Normal Secondary Characteristics Mullerian Anomalies Mullerian agenesis (Mayer-Rokitansky-Kuster-Hauser syndrome) Imperforate hymen Transverse vaginal septum M-K-K-H is second most common cause of primary amenorrhea (1/4000) Mullerian aplasia -> nl breast devlpmt, body hair, blind vaginal pouch Check for renal abnormalities (present in 34%), skeletal abnormalities (12%) M-K-K-H is second most common cause of primary amenorrhea (1/4000) Mullerian aplasia -> nl breast devlpmt, body hair, blind vaginal pouch Check for renal abnormalities (present in 34%), skeletal abnormalities (12%)

14: Mayer-Rokitansky-Kuster-Hauser Syndrome (utero-vaginal agenesis) 15% of primary amenorrhea Normal secondary development & external female genitalia Normal female range testosterone level Absent uterus and upper vagina & normal ovaries Karyotype 46-XX 15-30% renal, skeletal and middle ear anomalies

15: Imperforate Hymen

16: Androgen Insensitivity Normal breasts but no sexual hair Normal looking female external genitalia Absent uterus and upper vagina Karyotype 46, XY Male range testosterone level Treatment : gonadectomy after puberty + HRT

17: Primary Amenorrhea Evaluation Pregnancy test Physical exam to determine presence of uterus FSH Karyotype

18: Primary Amenorrhea Treatment Cyclic estrogen/progestin Remove gonadal streaks if XY or mosaic Increased (52%) risk of gonadoblastomas, dysgerminomas, and yolk sac tumors Pulsatile GnRH for ovulation induction in select patients Surgical resection of intrauterine, cervical, and vaginal adhesions/septa

19: Secondary Amenorrhea Pregnancy! CNS disorders Pituitary gland Thyroid Ovary Uterus Systemic disorders Renal failure, liver disorders, DM Medications: anti-psychotics, reserpine

20: Secondary Amenorrhea CNS disorders Chronic hypothalamic anovulation Stress Increased exercise levels Anorexia nervosa Head trauma Space-occupying lesions

21: Secondary Amenorrhea Pituitary disorders Hyperprolactinemia Prolactinoma Medications PCOS Renal failure Hypoprolactinemia Pituitary resection Sheehan’s syndrome Thyroid disorders Hyper- or hypothyroidism

22: Secondary Amenorrhea Ovulation disorders Polycystic ovarian syndrome Premature ovarian failure Uterine abnormalities Asherman’s syndrome Cervical stenosis Drug-induced amenorrhea Hormonal contraceptives GnRH analogues

23: Asherman’s Syndrome

24: Secondary Amenorrhea History Nutrition/exercise habits, weight change Sexual/contraceptive practice History of uterine/cervical surgery Physical exam Height/weight Hirsutism Galactorrhea Estrogen status of tissues Laboratory BhCG ?PRL & TSH ? progesterone challenge ? FSH ? if high ?karyotype Karyotype for patients with premature ovarian failure <30yo If hirsutism is present, consider PCOS, congenital adrenal hyperplasia, Cushing’s, or ovarian tumors: check free testosteroneKaryotype for patients with premature ovarian failure <30yo If hirsutism is present, consider PCOS, congenital adrenal hyperplasia, Cushing’s, or ovarian tumors: check free testosterone

26: Secondary Amenorrhea Treatment goals Discovery and treatment of underlying disorder Hormone replacement Menses every 1-3 months Pregnancy Ovulation induction GnRH pump FSH/LH Purpose for inducing menses at least every 3 months is to prevent endometrial hyperplasia and cancerPurpose for inducing menses at least every 3 months is to prevent endometrial hyperplasia and cancer

27: Amenorrhea 26 yo Gravida 0 with menarche at age 14 presents with one-year history of amenorrhea.

28: Amenorrhea Sexually active, using condoms No recent change in weight, skin, hair Occasional heat intolerance No cyclic pain No gynecologic surgery Regular menses (every 28-30 days) prior to past year

29: Amenorrhea Exam Overweight No galactorrhea Normal hair distribution Normal pelvic exam Pregnancy test Progestin challenge, TSH, serum prolactin Estrogen/progestin cycle, FSH

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