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Amenorrhea
- 1. a-men-o-rrhea Rawa Muhsin lack of -- monthly -- flow
- 5. Definition • No menses at age – 15 yr in the presence of secondary sexual characteristics – 13 yr in the absence of secondary sexual characteristics
- 6. Etiology Hypothalamus 1. Functional 2. Congenital 3. Constitutional 4. Infiltrative disease, trauma, radiation 5. Prader-Willi, Laurence- Moon-Biedl Ovary 1. Gonadal dysgenesis 2. Polycystic ovary syndrome Müllerian structures 1. Imperforate hymen 2. Transverse vaginal septum 3. Vaginal agenesis (MRKH) Receptors and enzymes 1. Androgen insensitivity 2. 5-alpha-reductase deficiency 3. CYP17 deficiency 4. Vanishing testes syndrome Pituitary 1. Hyperprolactinemia 2. Infiltrative diseases, trauma, radiation
- 7. Etiology
- 8. Diagnostic approach • Step 1: History – Secondary sexual characteristics and height – Symptoms of virilization – Stress, weight, diet, and exercise – Galactorrhea – Headaches, visual field defects, polyuria, polydipsia – Neonatal and childhood health – Drugs – Family history of delayed puberty
- 9. Diagnostic approach • Step 2: Physical examination – Height, weight, BMI – Breast development – Genital examination – Skin examination – Features of Turner syndrome
- 10. Diagnostic approach and the anorexic winners are…
- 17. Diagnostic approach • Step 3: Investigations – Uterus absent • karyotype • serum testosterone – Uterus present • FSH (then karyotype or MRI) • prolactin and TSH • serum testosterone and DHEA-S • CYP17 deficiency tests
- 18. Treatment • Aims: underlying pathology, fertility, complications • Hypothalamic and pituitary causes – Functional → weight gain, reduce exercise intensity, resolution of illness or emotional stress, hormone replacement, exogenous gonadotrophins or pulsatile GnRH – Congenital → exogenous gonadotrophins or pulsatile GnRH – Infiltrative diseases and hyperprolactinemia → specific treatment
- 19. Treatment • Ovarian causes – Gonadal dysgenesis → hormone replacement therapy, donor oocytes – PCOS → relief of hirsutism, resumption of menses, fertility, endometrial hyperplasia, obesity, metabolic defects
- 20. Treatment • Anatomical causes – Corrective surgery – Absent müllerian structures → creation of neovagina, surrogacy – Psychological counseling • Enzyme and receptor defects – Surgery to remove testicular substance – Psychological counseling
- 22. Definition • Absence of menses for more than – 3 cycles or – 6 months • in women who previously had menses
- 24. Etiology Hypothalamus 1. Functional 2. Infiltrative diseases 3. Trauma, radiation Ovary 1. Polycystic ovary syndrome 2. Primary ovarian insufficiency Uterus 1. Asherman syndrome 2. Infections, TB Systemic illness 1. Celiac disease 2. Thyroid disease 3. Pulmonary TB, uremia, Addison Pituitary 1. Hyperprolactinemia 2. Sellar masses 3. Infiltrative diseases 4. Sheehan, radiation
- 25. Diagnostic approach • Step 1: Rule out pregnancy! – serum beta-hCG measurement
- 26. Diagnostic approach • Step 2: History – Stress, weight, diet, exercise – Hot flashes, vaginal dryness, poor sleep, ↓ libido – Acne, hirsutism, deepening of voice – Galactorrhea – Headaches, visual field defects, polyuria, polydipsia – Obstetric catastrophe, endometritis, D&C – Past medical history – Drugs
- 27. Diagnostic approach • Step 3: Physical examination – Height, weight, BMI – Skin examination – Genital examination – Parotid glands and teeth
- 30. Diagnostic approach • Step 4: Investigations – FSH (then MRI) – Prolactin and TSH (then MRI) – Estrogen status – Progestin challenge (then HSG or hysteroscopy) – Serum testosterone, 17-HP, DHEA-S – Transferrin, ACE, blood glucose, Hb A1c
- 31. Diagnostic approach • Diagnostic criteria (Rotterdam) for PCOS are two out of three • CAH, Cushing syndrome, and androgen-secreting tumors must be excluded
- 32. Treatment • Hypothalamic – Lifestyle changes → adequate caloric intake, ↓ exercise, relief of stress – Cognitive behavioral therapy – Leptin administration – Estrogen therapy
- 33. Treatment • Hyperprolactinemia – Dopamine agonists (cabergoline, bromocriptine, pergolide, quinagolide) – Transsphenoidal surgery ∓ radiation therapy – Estrogen + progestin – Treat hypothyroidism – If due to antipsychotic drug → add dopamine agonist, change to quetiapine, add aripiprazole (e.g. to risperidone), add estrogen and progestin
- 34. Treatment • Primary ovarian insufficiency – Oral contraceptive pill – Replacement dose of estrogen and progesterone • Asherman syndrome – Hysteroscopic lysis – Long-term high-dose estrogen, IUD, or Foley catheter
- 35. Treatment • Polycystic ovary syndrome – Hirsutism and acne → OCP ∓ antiandrogen, GnRH agonists, mechanical methods – Androgenetic alopecia → finasteride, minoxidil, surgery – Endometrial protection → OCP, progestin – Infertility → weight loss, clomiphene, + adjuvants, FSH injections, ovarian surgery, IVF – Treat obesity, insulin resistance, dyslipidemia, OSA, NASH
- 36. Exercise
- 37. The End
Editor's Notes
- The average adult menstrual cycle lasts 28 to 35 days. There is relatively little cycle variability among women between the ages of 20 and 40 years. Sudden positive feedback effect, resulting in a 10-fold increase in serum LH concentrations and a smaller rise in serum FSH concentrations. The oocyte is released from the follicle at the surface of the ovary approximately 36 hours after the LH surge.
- In Lecture Notes investigation is done at 16 if secondary characteristics are absent, 18 if present.
- Gonadal dysgenesis — 50 percent Hypothalamic — 20 percent Mullerian — 20 percent Pituitary — 5 percent Others (including PCOS) — 5 percent craniopharyngioma, germinoma, and Langerhans cell histiocytosis, hemochromatosis, sarcoidosis prolactin inhibits GnRH Vaginal agenesis, also known as müllerian agenesis or Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome, refers to congenital absence of the vagina with variable uterine development. in 5-alpha-reductase deficiency testosterone-dependent processes are intact, including male pattern hair growth, muscle mass, and voice deepening in CYP17 deficiency adrenal and gonadal sex steroids are not produced so that affected subjects typically present as phenotypic females with hypertension (due to mineralocorticoid excess)
- Poor neonatal health in CAH, poor childhood health in hypothalamic/pituitary disorders. Drugs taken for diseases which themselves cause amenorrhea (e.g. sarcoidosis) or the drugs cause amenorrhea (dopamine antagonists, OCP)
- Genital examination should be performed for clitoral size, pubertal hair development, intactness of the hymen, depth of the vagina, and presence of a cervix, uterus, and ovaries.
- A. Vulva and vestibule showing vaginal agenesis.
- Photograph of a 17-year-old woman with androgen insensitivity syndrome (AIS). The external genitalia are female, but the patient has a 46, XY karyotype and testes. B, Photomicrograph of a section through a testis removed from the inguinal region of this woman showing seminiferous tubules lined by Sertoli cells. There are no germ cells, and the interstitial cells are hypoplastic.
- A grey-black, papillomatous thickening of the skin at the flexor areas. It is usually, symmetrical and velvety to the touch. Acanthosis nigricans (AN) is found most commonly around the posterolateral neck, axillae, groin and abdominal folds. Causes The key factor in most cases is insulin resistance. 1. Type 2 diabetes 2. Obesity, Cushing’s syndrome, PCOS 3. Acromegaly, malignancy 4. Other states of hyperinsulinaemia
- androgen-secreting tumor CYP17 if hypertensive → rise in serum progesterone (>3 ng/mL) and deoxycorticosterone and low serum 17-alpha-hydroxyprogesterone
- estrogen-progestin replacement therapy should be given to those not seeking fertility to prevent osteoporosis and heart disease
- principal estrogen produced by the functioning premenopausal ovary is 17beta-estradiol; mean serum estradiol level averaged across the menstrual cycle is approximately 104 pg/mL transdermal estradiol (usually 100 mcg daily) or oral estradiol (usually 2 mg/day) 10 mg of medroxyprogesterone acetate per day for the first 12 calendar days of each month
- There is a high risk (30 percent) of developing a gonadal tumor (gonadoblastoma or dysgerminoma) so that early extirpation of testicular remnants is recommended. gonadectomy should be delayed until after puberty in patients with complete androgen insensitivity syndrome
- In addition, at age 12 or 13, if cyclic pelvic pain is present, obstructed müllerian outflow track, a cause of both primary amenorrhea and pelvic pain, should be considered in the differential diagnosis.
- Ovary — 40 percent Hypothalamus — 35 percent Pituitary — 19 percent Uterus — 5 percent Other — 1 percent Infiltrative includes lymphoma; infiltrative cases usually have severe headache, change in personality, marked mood changes Sellar masses include pituitary adenomas, craniopharyngiomas, meningiomas, cysts
- women with hypothalamic amenorrhea do not usually have menopausal symptoms
- On exam, the vagina typically appears pale, with lack of the normal rugae. The external genitalia may show scarce pubic hair, diminished elasticity and turgor of the vulvar skin, introital narrowing or decreased moisture, and fusion or resorption of the labia minora. Parotid gland swelling and/or erosion of dental enamel would suggest an eating disorder (bulimia nervosa).
- Loss of labial and vulvar fullness, narrow introitus, loss of urethral meatal turgor, minimal vaginal moisture, pallor of urethral and vaginal epithelium.
- Clinical evidence of hyperandrogenism → serum total testosterone; also 17-hydroxyprogesterone at initial visit to rule out nonclassic 21-hydroxylase deficiency; DHEA-S to look for an adrenal source of androgens. Progestin withdrawal test, measurement of endometrial thickness on ultrasound, or a serum estradiol. High serum transferrin saturation may indicate hemochromatosis, high serum angiotensin-converting enzyme values sarcoidosis, and high fasting blood glucose or hemoglobin A1c values diabetes mellitus. Progestin challenge → medroxyprogesterone acetate 10 mg for 10 days, no withdrawal bleeding in Asherman
- criteria: oligo- and/or anovulation; clinical and/or biochemical signs of hyperandrogenism; polycystic ovaries (by US) clinical (hirsutism, acne, or male pattern balding) or biochemical (high serum androgen concentrations) ultrasound criteria for PCOS ≥ 12 follicles / ovary; each follicle < 10 mm in diameter; ovarian volume > 10 mL follicle distribution and stromal echogenicity, and volume suggested to be removed from criteria ovarian volume = 0.5 x length x width x thickness US features alone not sufficient for diagnosis; one ovary sufficient for diagnosis; transvaginal US should be used other criteria systems are NIH consensus criteria (no US criteria) and AES criteria
- Estrogen therapy for low bone density.
- estrogen for 30 days (+ progesterone in last 10 days), IUD for 3 months, Foley for 10 days + antibiotic
- adjuvant = addition of dexamethasone, pretreatment with oral contraceptives, or metformin anti-androgen = spironolactone, finasteride, cyproterone acetate; added after 6 mo if suboptimal response metformin not helpful for hirsutism and acne nor endometrial protection endometrial protection from endometrial hyperplasia, DUB, and endometrial cancer
- Turner AIS Hypogonadotrophic hypogonadism Prolactinoma PCOS POF