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Sexual & Reproductive Health Across the Female Life Cycle

Gynecology Midterm Study Guide

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1. OVERVIEW: THE HPO AXIS (Foundation for Everything)

• Hypothalamus - secretes GnRH (a decapeptide, also called LHRH) from neurons in the arcuate nucleus. GnRH must be secreted pulsatilely - continuous infusion causes downregulation and shuts off FSH/LH. Half-life of GnRH is only 2-4 minutes.
• Anterior Pituitary - responds to GnRH pulses by releasing FSH and LH
• Ovary - responds to FSH/LH to produce follicular growth, ovulation, corpus luteum formation

• High-frequency GnRH pulses → favors LH secretion
• Low-frequency pulses → favors FSH secretion
• Follicular phase: frequent, small-amplitude pulses
• Luteal phase: less frequent, higher-amplitude pulses

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2. NEONATAL PERIOD

• Neonatal vulvovaginal discharge/pseudomenstruation is normal - due to withdrawal from maternal estrogen crossing the placenta
• Vaginal mucosa is estrogenized at birth, then becomes atrophic within weeks as maternal estrogen clears
• Clitoromegaly, labial fusion, or ambiguous genitalia at birth warrants urgent workup (rule out congenital adrenal hyperplasia - CAH - the #1 cause of female pseudohermaphroditism)
• The labia minora are relatively prominent at birth due to maternal estrogen exposure

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3. CHILDHOOD (Pre-pubertal, ages ~2-8)

• Prepubertal vulvovaginitis - most common gynecologic complaint in children. Causes: poor hygiene, non-specific bacterial infections, pinworms. Vaginal pH is alkaline (no estrogen). Treated with hygiene measures ± topical estrogen cream.
• Labial adhesions - common, estrogen-deficient state leads to adhesion of labia minora. Treat with topical estrogen cream.
• Foreign body vaginitis - recurrent, bloody or malodorous discharge; toilet paper is the most common culprit. Examination ± vaginoscopy needed.
• Sexual abuse - any unexplained genital trauma, STI in a child, or behavioral changes must prompt evaluation.
• Ovarian cysts - mostly functional; significant cysts may torse.

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4. PUBERTY

• Stage I = prepubertal
• Stage II = breast budding / sparse pubic hair (earliest sign of puberty)
• Stage III = breast/areola enlarge / darker, curlier hair
• Stage IV = areola and nipple form secondary mound / adult hair, not spread to thighs
• Stage V = adult mature breast / adult pattern spread to medial thighs

• Precocious puberty = sexual development before age 8 in girls (isosexual precocious puberty). Can be:
  • Central (GnRH-dependent) - early activation of HPO axis. Treat with GnRH agonist (paradoxically suppresses HPO axis via downregulation)
  • Peripheral (GnRH-independent) - autonomous sex hormone production (McCune-Albright syndrome, granulosa cell tumor, exogenous estrogen)
• Delayed puberty = no breast development by age 13, or no menarche by age 15 (or >5 years after thelarche)
  • Most common cause: constitutional delay (normal variant)
  • Pathologic: hypogonadotropic (low FSH/LH - e.g., Kallmann syndrome) vs. hypergonadotropic (high FSH/LH - e.g., Turner syndrome 45,X)

• First cycles are commonly anovulatory (irregular, painless)
• Regular ovulatory cycles typically established within 1-2 years

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5. REPRODUCTIVE YEARS (approx. ages 16-45)

The Normal Menstrual Cycle

• Cycle length: 21-35 days (mean 28 days)
• Duration of flow: 2-6 days
• Blood loss: 20-60 mL (>80 mL = heavy menstrual bleeding)
• Two phases: Ovarian cycle (follicular + luteal) / Uterine cycle (proliferative + secretory)

Hormonal Sequence (Step by Step)

1. Early follicular phase (Days 1-5): FSH rises as corpus luteum involutes → recruits follicular cohort
2. Mid-follicular (Days 6-10): Growing follicles secrete estradiol → endometrium proliferates. Rising estrogen + inhibin B suppress FSH (negative feedback). LH initially suppressed.
3. Late follicular (Days 10-13): Estradiol rises sharply → LH surge triggered (biphasic response - high sustained estradiol switches from negative to positive feedback). LH surge = proximate cause of ovulation
4. Ovulation (Day ~14): Occurs 24-36 hours after LH surge. FSH mid-cycle surge also occurs (progesterone-mediated).
5. Luteal phase (Days 15-28): Corpus luteum secretes progesterone + estradiol. Endometrium becomes secretory. Inhibin A secreted by corpus luteum.
6. Late luteal / menses: If no implantation, corpus luteum involutes → estrogen and progesterone fall → endometrium shed.

Key Hormones Summary

Common Reproductive-Age Gynecologic Conditions

• PALM (structural): Polyp, Adenomyosis, Leiomyoma, Malignancy/hyperplasia
• COEIN (non-structural): Coagulopathy, Ovulatory dysfunction, Endometrial, Iatrogenic, Not yet classified

• Primary - no pelvic pathology; prostaglandin-mediated uterine cramping. Tx: NSAIDs (first-line), OCP
• Secondary - due to pathology (endometriosis, fibroids, adenomyosis). Onset later in life, worsening dysmenorrhea

• Start at age 21 (regardless of sexual debut)
• Age 21-29: Pap smear every 3 years
• Age 30-65: Pap + HPV co-test every 5 years (preferred) or Pap alone every 3 years
• Adolescents: NOT screened until age 21 (even if HIV-negative)

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6. PRE-MENOPAUSAL / PERIMENOPAUSE (Menopausal Transition, approx. ages 40-51)

• Ovarian follicular reserve depletes → FSH rises (FSH >10-25 IU/L in early perimenopause)
• Estradiol levels fluctuate erratically - can be high or low
• Inhibin B falls (first detectable change)
• Cycles become irregular, often anovulatory
• AMH (anti-Müllerian hormone) falls progressively - best marker of ovarian reserve

• Stage -2 (early menopausal transition): variable cycle length, FSH rising
• Stage -1 (late menopausal transition): ≥2 skipped cycles, amenorrhea ≥60 days

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7. MENOPAUSE

• FSH markedly elevated (>40 IU/L)
• LH elevated
• Estradiol very low (<20 pg/mL)
• No progesterone production
• Testosterone also decreases (ovaries continue to produce some androgens post-menopause)

• Osteoporosis - estrogen loss accelerates bone resorption. Bone loss fastest in first 3-5 years post-menopause. Screen with DXA.
• Cardiovascular disease - estrogen had cardioprotective effects; menopause increases CVD risk.
• Urogenital atrophy - GSM (genitourinary syndrome of menopause) affects up to 50% of postmenopausal women.

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8. POST-MENOPAUSE

Hormone Therapy (HT)

• Systemic HT (oral or transdermal estrogen ± progestogen):
  • Indicated for: moderate-to-severe vasomotor symptoms, GSM
  • If uterus intact: must add progestogen (to prevent endometrial hyperplasia/carcinoma)
  • Hysterectomized women: estrogen alone is sufficient
  • WHI study showed increased breast cancer risk with combined E+P (but mainly with oral conjugated equine estrogen + MPA); transdermal estradiol + micronized progesterone may be safer
  • Timing hypothesis: HT started within 10 years of menopause or before age 60 has better cardiovascular risk profile ("window of opportunity")
• Local/vaginal estrogen: For GSM only; minimal systemic absorption; does NOT require progestogen even with uterus intact (very low dose)

Non-Hormonal Options

• SSRIs/SNRIs (paroxetine FDA-approved) - for hot flashes
• Gabapentin - for hot flashes and sleep
• Ospemifene (SERM) - oral treatment for dyspareunia
• Black cohosh (Cimicifuga racemosa) - traditional herbal remedy; modest evidence; may act as SERM at serotonin receptors; does NOT contain phytoestrogens
• Phytoestrogens (soy isoflavones, red clover) - weak evidence

Bone health

• Calcium 1200 mg/day + Vitamin D 800-1000 IU/day
• Weight-bearing exercise
• Bisphosphonates (alendronate, risedronate) for established osteoporosis
• DEXA screening: all women ≥65, or earlier if risk factors

Cardiovascular

• Lifestyle: diet, exercise, smoking cessation
• HT is NOT recommended for primary or secondary CVD prevention

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9. QUICK-REFERENCE TABLE: Hormonal Profile Across Life Stages

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10. HIGH-YIELD EXAM POINTS SUMMARY

1. GnRH must be pulsatile - continuous exposure causes receptor downregulation (basis for GnRH agonist therapy in precocious puberty, endometriosis, fibroids)
2. Ovulation trigger = LH surge, occurs 24-36 hours before ovulation
3. Menarche = last event of puberty; first sign = thelarche (breast budding)
4. Precocious puberty = < 8 years; Delayed puberty = no breast development by 13
5. Normal menstrual cycle = 21-35 days, 2-6 days flow, 20-60 mL blood loss
6. Perimenopause = irregular cycles + vasomotor symptoms; FSH rising but variable
7. Menopause = confirmed by 12 months amenorrhea; FSH >40; average age 51
8. POI (Premature Ovarian Insufficiency) = menopause before age 40
9. HT with uterus intact = MUST add progestogen (estrogen alone causes endometrial hyperplasia)
10. Cervical cytology starts at age 21 regardless of sexual debut
11. GSM (genitourinary syndrome of menopause) = vaginal atrophy, dryness, dyspareunia, recurrent UTIs
12. PALM-COEIN = classification system for abnormal uterine bleeding
13. Inhibin B falls first in perimenopause (before FSH rises); AMH is the best ovarian reserve marker
14. Anovulatory cycles are common just after menarche AND just before menopause
15. Postmenopausal bleeding = must rule out endometrial cancer first (endometrial biopsy)

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