5. Definition
⢠No menses at age
â 15 yr in the presence of secondary sexual
characteristics
â 13 yr in the absence of secondary sexual
characteristics
8. Diagnostic approach
⢠Step 1: History
â Secondary sexual characteristics and height
â Symptoms of virilization
â Stress, weight, diet, and exercise
â Galactorrhea
â Headaches, visual field defects, polyuria, polydipsia
â Neonatal and childhood health
â Drugs
â Family history of delayed puberty
9. Diagnostic approach
⢠Step 2: Physical examination
â Height, weight, BMI
â Breast development
â Genital examination
â Skin examination
â Features of Turner syndrome
31. Diagnostic approach
⢠Diagnostic criteria (Rotterdam) for PCOS are two out
of three
⢠CAH, Cushing syndrome, and androgen-secreting
tumors must be excluded
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 â 50 percent
Hypothalamic â 20 percent
Mullerian â 20 percent
Pituitary â 5 percent
Others (including PCOS) â 5 percent
craniopharyngioma, germinoma, and Langerhans cell histiocytosis, hemochromatosis, sarcoidosis
prolactin inhibits GnRH
Vaginal agenesis, also known as mĂźllerian agenesis or Mayer-Rokitansky-KĂźster-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, Cushingâs syndrome, PCOS
3. Acromegaly, malignancy
4. Other states of hyperinsulinaemia
androgen-secreting tumor
CYP17 if hypertensive â rise in serum progesterone (>3Â ng/mL)Â 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 104Â pg/mL
transdermal estradiol (usually 100 mcg daily) or oral estradiol (usually 2Â 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 mĂźllerian outflow track, a cause of both primary amenorrhea and pelvic pain, should be considered in the differential diagnosis.
Ovary â 40 percent
Hypothalamus â 35 percent
Pituitary â 19 percent
Uterus â 5 percent
Other â 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 â 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 â 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 ⼠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
