Menstrual Disorders and Pelvic Pain¶

Chapter 405 | Part 12: Endocrinology and Metabolism · Part 12 – Endocrinology & Metabolism · Chapter 405

Key Clinical Points¶

Pregnancy must be excluded in all cases of amenorrhea or menstrual irregularity using a β-hCG test.
Primary amenorrhea is defined as absence of menarche by age 15 (with secondary sexual characteristics) or 13 (without).
Secondary amenorrhea is defined as cessation of menses for 3–6 months (3 months if cycles are regular, 6 months if irregular).
PALM-COEIN classifies AUB into structural (Polyp, Adenomyoma, Leiomyoma, Malignancy/hyperplasia) and nonstructural causes.
PCOS diagnosis requires 2 of 3 Rotterdam criteria: oligo/anovulation, hyperandrogenism, or polycystic ovaries on ultrasound (≥20 antral follicles or volume ≥10 cm³).
Letrozole is the first-line treatment for ovulation induction in PCOS; clomiphene citrate follows.
Acute pelvic pain requires immediate evaluation for ectopic pregnancy, PID, ovarian torsion, or ruptured cyst.
Chronic pelvic pain assessment includes pelvic ultrasound and referral for extra-pelvic causes (GI, urological, etc.).
Functional hypothalamic amenorrhea is characterized by low gonadotropins and normal prolactin.
Hormone replacement therapy (HRT) is essential in amenorrhea to provide bone and cardiovascular protection.

DEFINITION & CLASSIFICATION¶

• Amenorrhea: Absence of menstrual periods. • Primary Amenorrhea: Never had a period. • Evaluation by age 15 (with secondary sexual characteristics) or 13 (without). • Secondary Amenorrhea: Cessation of menses for 3–6 months. • 3 months if cycles are regular → 6 months if irregular. • Abnormal Uterine Bleeding (AUB): Irregularities in cycle frequency, cyclicity, duration, or volume outside of pregnancy. • Normal Cycle: Every 21–35 days, lasting 4–7 days, with ≤80 mL blood loss. • PALM-COEIN Classification: • Structural (PALM): Polyp, Adenomyosis, Leiomyoma (submucosal or other), Malignancy/hyperplasia. • Nonstructural (COEIN): Coagulopathy, Ovulatory dysfunction, Endometrial, Iatrogenic, Not yet classified.

Classification Systems¶

• Table 1 (PALM-COEIN): Categorizes AUB into Structural (Polyp, Adenomyosis, Leiomyoma, Malignancy/hyperplasia) and Nonstructural (Coagulopathy, Ovulatory dysfunction, Endometrial, Iatrogenic, Not yet classified).

EPIDEMIOLOGY¶

• Primary Amenorrhea: Rare; <1% of the female population. • Secondary Amenorrhea: 3–5% of women. • Irregular Cycles: Common for up to 3 years after menarche and 1–2 years before menopause. • AUB Prevalence: Affects up to one-third of women between menarche and menopause.

ETIOLOGY & PATHOPHYSIOLOGY¶

• Hormonal Regulation: Mediated by feedback loops involving estradiol, progesterone, inhibin A/B, GnRH, FSH, and LH. • Hypogonadotropic Hypogonadism: • Low estrogen + Normal/Low LH/FSH. • Causes: Anatomic, genetic, or functional abnormalities of hypothalamus or pituitary. • Associated features: Short stature, diabetes insipidus, galactorrhea, headache. • Hypergonadotropic Hypogonadism: • Ovarian failure (Premature Ovarian Insufficiency/POI) in women <40 years old. • Mechanism: Loss of negative feedback → Increased FSH and LH. • Polycystic Ovary Syndrome (PCOS): • Diagnosis of exclusion (must rule out hypothyroidism, hyperprolactinemia, adrenal sources). • Pathophysiology: • GnRH pulsatility abnormalities → Elevated LH → Increased ovarian androgens. • Insulin resistance (skeletal muscle/adipose) → Increased insulin-stimulated androgen production. • Genetic factors: ~19 loci associated with PCOS phenotypes.

CLINICAL FEATURES¶

• Primary Amenorrhea: • Evaluation by age 15/16 (normal growth/secondary characteristics). • Evaluation by age 13 (no secondary features or height <3rd percentile). • Evaluation by age 12-13 (breast development + cyclic pelvic pain). • Within 2 years of breast development if menarche hasn't occurred. • Secondary Amenorrhea: • Trigger evaluation: 3 months of amenorrhea or 6 months if cycles were irregular. • Trigger evaluation: Intermenstrual intervals >35 or 7 days. • Acute Pelvic Pain: • Presentation: Bilateral lower abdominal pain, potentially with fever, peritoneal signs, or hemodynamic instability. • Risk Factors (PID): Age <25, multiple partners, STIs, recent uterine procedures. • Ovarian Torsion: Acute onset of unilateral, intermittent pain. • Chronic Pelvic Pain: • Complex condition; involves gynecologic, urologic, or gastrointestinal organs. • Common causes: Endometriosis, fibroids, adenomyosis, adnexal pathology.

DIFFERENTIAL DIAGNOSIS¶

• Amenorrhea: • Structural/Outflow Tract: Transverse vaginal septum, imperforate hymen, Müllerian agenesis (WNT4 mutation), Androgen insensitivity syndrome (AIS). • AIS: 46,XY karyotype; lack of androgen receptor response → no pubic/axillary hair. • Distinction from Müllerian agenesis: AIS has testosterone in male range; Müllerian agenesis does not. • Asherman’s Syndrome: Secondary amenorrhea due to uterine adhesions (90% from prior surgery). • Pelvic Pain: • Ectopic pregnancy, PID, ovarian cyst rupture, endometriosis, fibroids, threatened abortion.

DIAGNOSTIC APPROACH¶

Initial Workup: • Obtain focused menstrual history (type, location, radiation, recurrence). • Rule out pregnancy immediately with β-hCG. • Physical exam including perineal examination and ultrasound imaging.
Amenorrhea Diagnostic Algorithm (Flowchart 1):
Step 1: Assess uterus/outflow tract.
If Abnormal → Karyotype Analysis.
Karyotype Abnormal → Androgen insensitivity syndrome or 5α-reductase deficiency.
Karyotype Normal → History of uterine instrumentation OR Normal prolactin/No response to trial of estrogen/progesterone → Asherman's syndrome.
Step 2: If uterus/outflow tract is Normal → Perform β-hCG.
Positive → Pregnancy.
Negative → Assess FSH levels.
High → Premature ovarian insufficiency or Turner syndrome.
Normal/Low → Proceed to further differentiation:
Hyperandrogenism, Testosterone rise, etc. → R/o 21-hydroxylase deficiency, Tumor, or PCOS.
Prolactin high → Pituitary causes.
Prolactin normal → Hypothalamic causes.
TSH abnormal → Thyroid causes.
Testosterone high (with FSH Normal/low) → Adrenal causes or PCOS.
Karyotype abnormal → Turner's syndrome.
History of uterine instrumentation → Asherman's syndrome.
History of sexual abuse → Müllerian agenesis.
5α-reductase deficiency → Virilization at puberty.
PCOS Diagnosis (Table 2):
Requires 2 of 3 criteria:
Oligo- or Anovulation: Irregular menses (<8 per year).
Hyperandrogenism: Elevated testosterone or Modified Ferriman-Gallwey score >4–6.
Polycystic Ovaries: ≥20 antral follicles, volume ≥10 cm³, or elevated AMH.
Pelvic Pain Differentiation (Table 3):
Acute: Mittelschmerz, PID, Ruptured/hemorrhagic ovarian cyst, Ectopic pregnancy, Endometritis, Acute growth/degeneration of uterine myoma, Threatened abortion.
Chronic: Mittelschmerz (Cyclic), Chronic PID, Endometriosis, Uterine fibroids, Adenomyosis, Pelvic adhesions, Pelvic malignancy, Vulvodynia, Pelvic congestion syndrome, Tuberculous salpingitis, History of sexual abuse.

MANAGEMENT & TREATMENT¶

Amenorrhea Management:
Hormone Replacement: Estrogen and progestin for bone/cardiovascular protection.
Fertility (Hypogonadotropic): Exogenous FSH and LH.
POI: Consider oocyte donation.
PCOS Management:
Non-pregnancy goal: Combined hormonal contraceptives (lowest effective dose of estrogen) to regulate cycles and decrease androgens.
Hyperandrogenism (if no response after 6 months): Antiandrogens (spironolactone, flutamide).
Endometrial protection: Progestins (medroxyprogesterone acetate 10 mg or Prometrium 200 mg daily for 10–14 days every 3 months) or Levonorgestrel IUD.
Metabolic/Lifestyle: Screening for obesity, hypertension, glycemic control; Metformin for overweight/obese patients with metabolic risk.
Ovulation Induction: Letrozole (first-line) → Clomiphene citrate (+/- Metformin).
Acute Pelvic Pain Management:
PID: Immediate treatment.
Outpatient: 250 mg IM ceftriaxone + 14-day oral doxycycline 100 mg twice daily.
Inpatient: If high fever, nausea, vomiting, severe pain, or tubo-ovarian abscess.
Ovarian Cysts: Conservative management if no torsion suspected; Cystectomy (not oophorectomy) if surgery is required.
Ectopic Pregnancy:
Surgical: If unstable or signs of intraperitoneal bleeding.
Medical: Methotrexate for clinically stable, unruptured cases (effective in ~90%).
Fibroid Pain: NSAIDs for degenerating fibroids.
Chronic Pelvic Pain Management:
Referral to other specialists (GI, urology) as non-gynecologic causes are common.

COMPLICATIONS & PROGNOSIS¶

• PCOS Complications: Increased risk of early miscarriage, gestational diabetes, and gestational hypertension. • POI Complications: Risk of premature menopause; Turner's patients have increased cardiovascular risk in pregnancy.

SPECIAL POPULATIONS¶

• Adolescents: Evaluation for primary amenorrhea based on age, growth, and secondary sexual characteristics. • Pregnancy: Must be ruled out first; management of ectopic pregnancy depends on stability. • Turner's Syndrome: Associated with POI; requires caution in pregnancy due to cardiovascular risk.

KEY PEARLS & HIGH-YIELD POINTS¶

• Rule Out Pregnancy First: Always the first step in any amenorrhea workup. • FSH as a Gatekeeper: High FSH → Ovarian failure; Normal/Low → Central (Pituitary/Hypothalamic) or PCOS. • PCOS Treatment Hierarchy: Letrozole is 1st line for ovulation induction; Combined Hormonal Contraceptives are 1st line for cycle regulation. • PID Urgency: Immediate treatment required to prevent infertility and ectopic pregnancy risk.

Reference Tables¶

TABLE 405-1 Gynecologic Causes of Pelvic Pain Cyclic pelvic pain Noncyclic pelvic pain¶

Harrison's 22e, p.3136

	ACUTE	CHRONIC
Cyclic pelvic pain		Mittelschmerz Dysmenorrhea
	Pelvic inflammatory disease Ruptured or hemorrhagic ovarian cyst, endometrioma, or ovarian torsion Ectopic pregnancy Endometritis Acute growth or degeneration of uterine myoma Threatened abortion