Reproductive Hormonal Function & Disorders

Female Reproductive Anatomy & Physiology

  • External genitalia
    • Labia majora/minora & vestibular glands ➜ protection & lubrication
    • Clitoris ➜ homologous to penis; highly innervated, engorges during sexual arousal
  • Internal organs
    • Vagina ➜ copulation & birth canal
    • Cervix
    • Inlet to uterus; secretes mucus that varies with hormonal milieu
    • Acts as infection barrier & regulates sperm entry
    • Uterus (3 layers)
    • Endometrium (functional layer proliferates & sloughs each cycle)
    • Myometrium (smooth muscle; contracts to expel menses & for labor)
    • Perimetrium (outer serosa)
    • Fallopian (uterine) tubes
    • Fimbriae sweep ovum; ciliated epithelium propels gametes/zygote
    • Ovaries (4 histologic components)
    • Stroma (support)
    • Interstitial cells ➜ secrete estrogens
    • Follicles ➜ contain ova
    • Corpus luteum ➜ post-ovulation endocrine body (progesterone ± estrogen)

Female Reproductive Hormones

  • Hierarchy: Hypothalamus →\to GnRH ➜ Anterior Pituitary →\to FSH & LH ➜ Ovaries →\to Estrogen, Progesterone, Androgens
  • Estrogens (estradiol, estrone, estriol)
    • Secreted mainly by ovarian interstitial/follicular cells
    • Peak from end-menses →\to ovulation
    • Physiologic actions
    • Development of female reproductive tract & secondary sex traits (breast, fat deposition, hair)
    • Pubertal growth spurt; epiphyseal closure
    • Endometrial proliferation; cervical mucus becomes thin & spermic receptive
    • Bone conservation (↓ resorption), skin integrity, Na⁺/H₂O retention
  • Progesterone
    • Dominant luteal hormone (corpus luteum)
    • Thickens & maintains endometrium; relaxes myometrium (pregnancy maintenance)
    • Thermogenic ↑ core temp, contributes to N/V, constipation, edema

Pregnancy-Specific Hormones

  • hCG
    • Appears 2–32\text{–}3 days post-implantation; produced by trophoblast
    • Maintains corpus luteum (↑ estrogen & progesterone); basis of pregnancy tests
  • Prolactin (anterior pituitary) ➜ lactogenesis & maintenance
  • Oxytocin (posterior pituitary)
    • Uterine contractions, milk ejection, parent–infant bonding; stimulated by nipple stretch & skin-to-skin

Loss of Ovarian Hormones

  • Estrogen deficiency (oophorectomy, disease, menopause)
    • Vasomotor: hot flashes, night sweats
    • GU atrophy ➜ dryness, dyspareunia, incontinence, UTIs
    • Bone: ↓ density ➜ osteoporosis/fracture
    • CV: loss of cardioprotection ➜ ↑ MI/stroke risk
    • Skin: ↓ collagen ➜ thin, dry, wrinkled
    • Mood: ↓ serotonin modulation ➜ swings, depression
  • Progesterone deficiency
    • Unstable/over-proliferative endometrium ➜ irregular bleeding, ↑ endometrial cancer risk
    • Infertility (impaired implantation/maintenance)

Menstrual Cycle Phases (≈ 21–4021\text{–}40 d; mean 2828 d)

  1. Menstrual (d 1–51\text{–}5)
    • ↓ E & P as corpus luteum regresses ➜ functional endometrium sheds
  2. Follicular (d 11 to ovulation)
    • FSH stimulates cohort of follicles ➜ ↑ estradiol ➜ endometrial proliferation
    • Rising E first inhibits FSH (selection of dominant follicle), then triggers LH surge
    • LH surge ➜ ovulation @ mid-cycle
  3. Ovulation
    • Release of secondary oocyte; basal body temperature rises secondary to progesterone
  4. Luteal (post-ovulation ≈14≈14 d)
    • Corpus luteum secretes P > E ➜ endometrial secretory transformation
    • If no hCG, luteolysis ⇒ ↓ P/E ⇒ menses

Male Reproductive Hormones

  • Hypothalamus GnRH ➜ Pituitary FSH & LH
  • LH ➜ Leydig cells ➜ testosterone
    • Functions: secondary sex traits, spermatogenesis, libido, ↑ EPO & bone density, male fat pattern
    • Negative feedback on GnRH/LH/FSH
  • FSH ➜ Sertoli cells ➜ support spermatogenesis, produce inhibin

Spermatogenesis (≈ 64–7464\text{–}74 d)

  1. Spermatogonia (mitosis)
  2. Primary spermatocytes (meiosis I)
  3. Secondary spermatocytes (meiosis II)
  4. Spermatids ➜ spermiogenesis (tail, acrosome, mitochondria)
  5. Spermatozoa stored in epididymis until ejaculation

Infertility & Altered Reproductive Function

  • Defined: failure to conceive after 11 yr unprotected intercourse (≈ 10–15%10\text{–}15\% couples)
  • Female contributors
    • Anovulation/amenorrhea (hormonal, PCOS, thyroid)
    • Tubal/uterine pathology (adhesions, leiomyomas, PID)
    • Cervical mucus hostility; auto-antibodies to sperm
  • Male contributors
    • Hypogonadism (↓ T), varicocele, obstruction, poor semen parameters
  • Evaluation
    • Women: cycle history, pelvic exam, hormone panel (FSH, LH, E₂, P₄, TSH, prolactin, testosterone), pelvic US, HSG, laparoscopy
    • Men: H&P, hormonal assay (T, FSH, LH, prolactin, TFTs), semen analysis, scrotal US, genetic testing, post-ejaculatory urinalysis
  • Management
    • Lifestyle & STI prevention; counseling
    • Ovulation induction (clomiphene, letrozole)
    • Treat hyperprolactinemia (bromocriptine)
    • Surgery for fibroids/adhesions; IUI, IVF

Pelvic Inflammatory Disease (PID)

  • Ascending infection (N. gonorrhoeae, C. trachomatis, E. coli)
  • Pathogenesis: infection ➜ ↑ vascularity/edema ➜ purulent tubal exudate ➜ scarring/adhesions
  • Manifestations: pelvic pain, fever, purulent discharge, irregular bleeding, dyspareunia, CMT/Adnexal tenderness
  • Complications: TOA, pelvic adhesions, infertility, ectopic pregnancy, chronic pain
  • Diagnosis: clinical + TV-US, cultures, laparoscopy, ↑ WBC/CRP/ESR
  • Treatment: broad-spectrum antibiotics (ceftriaxone ± doxy ± metronidazole); hospitalize if severe; drain abscess surgically if needed

Polycystic Ovary Syndrome (PCOS)

  • Core features: hyperandrogenism, chronic anovulation, polycystic ovaries, insulin resistance, endometrial dysfunction
  • Pathophysiology
    • ↑ LH : FSH ratio ➜ ↑ ovarian androgen (testosterone)
    • Hyperinsulinemia amplifies androgen production
    • Follicles arrested ⇒ multiple sub-cm cysts
    • Unopposed estrogen ➜ endometrial hyperplasia/cancer risk
  • Clinical: hirsutism, acne, alopecia, obesity, AUB, infertility, metabolic syndrome
  • Management
    • Lifestyle: weight loss, low-GI diet, exercise
    • Combined OCPs for cycle control & ↓ androgen
    • Spironolactone for hirsutism; Metformin for insulin resistance; ovulation induction (letrozole/clomiphene) or IVF
    • Monitor for DM2, CV disease, endometrial pathology

Endometriosis

  • Ectopic endometrial implants (ovaries, tubes, peritoneum) cycle with hormones ➜ hemorrhage/inflammation ➜ fibrosis & adhesions
  • Symptoms: severe dysmenorrhea, chronic pelvic pain, dyspareunia, infertility, dyschezia/dysuria, menorrhagia
  • Diagnosis: laparoscopy (gold), US shows endometriomas (“chocolate cysts”)
  • Treatment: NSAIDs, hormonal suppression (OCPs, progestins, GnRH agonists), laparoscopic excision/ablation; hysterectomy ± BSO in refractory; IVF for fertility

Ovarian Cancer

  • 2nd most common gynecologic malignancy; 5th leading cause of female cancer death
  • Risk: family history (autosomal dominant BRCA1 / BRCA2), incessant ovulation, nulliparity, post-meno HRT
  • Protective: pregnancy, breastfeeding, OCPs (↓ ovulations)
  • Types
    • Epithelial (serous adenocarcinoma most common)
    • Germ-cell (often benign in adults)
    • Sex-cord stromal
  • Spread: exfoliation within peritoneum ➜ bowel/bladder; lymphatic to pelvic nodes; stage I–IV based on extent
  • Often asymptomatic; vague bloating, distension, pain when large
  • Diagnosis: pelvic exam, TVUS, CA-125125 & HE4 with ROMA, laparotomy/biopsy
  • Treatment: surgical debulking (TAH-BSO + omentectomy ± nodes) + chemo ± radiation; prognosis poor if stage III–IV (< 10%10\% 5-yr)

Menopause

  • Defined: 1212 mo amenorrhea due to ovarian failure (mean age 48–5548\text{–}55 yr)
  • Perimenopause lasts 4–84\text{–}8 yr; fluctuating cycles & symptoms
  • Hormonal profile: ↓ E₂ & P₄ ➜ loss of negative feedback ➜ ↑ FSH > LH but ovaries unresponsive
  • Manifestations
    • Vasomotor flashes, night sweats
    • GU atrophy (dryness, dyspareunia, incontinence)
    • ↓ breast & skin turgor, hair loss, brittle nails
    • Mood swings, “brain fog”, sleep disturbance (↓ E₂ & P₄, ↑ cortisol)
    • ↑ CV risk, osteoporosis
  • Management
    • Non-pharm: layered clothing, avoid triggers, exercise, phytoestrogens, Kegels, water-based lubricants
    • HRT (combined E+P) only for severe symptoms, lowest dose, shortest duration; topical vaginal E preferred

Erectile Dysfunction (ED)

  • Failure to attain/maintain erection sufficient for intercourse; prevalence ↑ with age
  • Physiology: Parasympathetic S2–S4 ➜ NO-mediated vasodilation ➜ blood fills corpora cavernosa ➜ venous occlusion; sympathetic discharge reverses
  • Etiologies
    1. Hormonal: ↓ T, ↑ prolactin, DM insulin resistance, ↑ cortisol
    2. Neurogenic: spinal/peripheral nerve injury
    3. Psychogenic: anxiety, depression
    4. Vascular: atherosclerosis, HTN, smoking
    5. Veno-occlusive failure
    6. Medications: anti-HTN, SSRIs, etc.
  • Work-up: H&P, T/LH/TSH/prolactin, nocturnal tumescence, vascular studies
  • Treatment: PDE-5 inhibitors (sildenafil, vardenafil, tadalafil), T replacement, psychotherapy, vacuum/penile implants

Benign Prostatic Hyperplasia (BPH)

  • Non-malignant prostate enlargement (peri-urethral zone); > 50%50\% men >60 yr, 90%90\% men >70 yr
  • Pathogenesis: aging ⟹ ↓ T : ↑ E ratio ➜ ↑ DHT accumulation ➜ stromal & glandular hyperplasia
  • Symptoms (LUTS) due to urethral compression
    • Hesitancy, weak stream, incomplete emptying, frequency, nocturia, urgency, dribbling, retention ± UTIs/stones
  • Diagnosis: DRE (soft, enlarged), PSA, uroflow/urodynamic studies, US
  • Treatment (symptomatic)
    • α-1 blockers (tamsulosin) relax smooth muscle
    • 5-α-reductase inhibitors (finasteride) ↓ DHT ➜ glandular atrophy
    • TURP, laser ablation, stents

Prostate Cancer

  • 2nd most common male cancer; adenocarcinoma (peripheral zone) driven partly by androgens
  • Risk: age, African ancestry, high fat diet, smoking, BRCA, HPC1 gene (chrom 1q241q24)
  • Early asymptomatic (peripheral location) ➜ detected by DRE (hard, asymmetric) & PSA screening
  • Later mimics BPH LUTS; bone metastases cause pain, pathologic fractures, paraneoplastic syndromes
  • Work-up: PSA, DRE, trans-rectal US, biopsy, bone scan; staged with TNM
  • Treatment: active surveillance, radical prostatectomy, radiation, androgen deprivation, chemo; 5-yr survival >99%99\% localized, ≈34%\approx34\% metastatic

Testicular Cancer

  • "Young man’s cancer" (ages 20–4020\text{–}40); highly curable if early
  • >90\% arise from germ cells
    1. Seminomas – resemble primitive sperm, slower, excellent prognosis
    2. Non-seminomas – embryonal, yolk sac, choriocarcinoma, teratocarcinoma; aggressive
  • Major risk: cryptorchidism (↑ risk 20–4020\text{–}40×). Theory: fetal germ-cell mutation + pubertal hormones
  • Staging: carcinoma in situ ➜ invasive; often malignant at DX
  • Presentation: painless testicular mass/enlargement, scrotal heaviness, mild discomfort
  • Diagnosis: self-exam, US, serum markers (β-hCG, AFP, LDH), inguinal orchiectomy (no trans-scrotal biopsy), imaging for spread
  • Treatment: radical orchiectomy ± radiation (seminoma) or combo chemo (non-seminoma). 5-yr survival ≥95%\ge95\% local seminoma; >70%70\% even with metastasis