13.7 Menstrual Disorders, Fibroids, Endometriosis & Early Pregnancy Complications

1. Amenorrhea

Primary amenorrhea: no menses by age 15 with secondary sexual characteristics, or by age 13 without them. Secondary amenorrhea: absence of menses for three months in a previously regular woman, or six months if irregular.

The evaluation sequence is fixed and is the exam content:

1. Pregnancy test. Always. Pregnancy is the most common cause of secondary amenorrhea.
2. Thyroid-stimulating hormone and prolactin.
3. Follicle-stimulating hormone, to separate ovarian from central causes.
4. Assess for hyperandrogenism if hirsutism or virilization is present.

Functional hypothalamic amenorrhea results from low energy availability — restrictive eating, excessive exercise, psychological stress — and produces low gonadotropins with low estradiol. It is a cause of premature bone loss, and the treatment is restoring energy availability, not prescribing an oral contraceptive to induce withdrawal bleeding, which masks recovery without protecting bone.

Asherman syndrome — intrauterine adhesions after instrumentation, usually dilation and curettage — produces amenorrhea with normal hormones and no withdrawal bleed after progestin.

2. Dysmenorrhea

Primary dysmenorrhea is prostaglandin-mediated cramping beginning with menarche, occurring with ovulatory cycles, starting just before or with flow and lasting one to three days. Examination is normal. NSAIDs started before or at the onset of flow are first-line, because they inhibit prostaglandin synthesis rather than merely blunting established pain; hormonal contraception is the other first-line option.

Secondary dysmenorrhea implies underlying pathology and is suggested by onset years after menarche, progressive worsening, pain outside menses, dyspareunia, abnormal bleeding, infertility or an abnormal examination. Causes include endometriosis, adenomyosis, fibroids, pelvic inflammatory disease, ovarian cysts and an intrauterine device.

3. Endometriosis

Endometrial-like tissue outside the uterus. The classic triad is dysmenorrhea, dyspareunia and infertility, often with cyclic bowel or bladder symptoms and chronic pelvic pain.

Key features:

• Symptom severity correlates poorly with disease extent — extensive disease may be nearly asymptomatic and minimal disease severely painful
• Diagnostic delay averages years, because symptoms are normalized as bad periods
• Examination may show uterosacral nodularity, a fixed retroverted uterus or an adnexal mass (endometrioma, the chocolate cyst)
• Definitive diagnosis is by laparoscopic visualization, but empiric medical therapy is appropriate first — surgery is not required before treating

Treatment: NSAIDs plus continuous combined hormonal contraception or a progestin; second-line options include GnRH agonists or antagonists with add-back therapy. Surgery is reserved for refractory pain, endometrioma or infertility.

4. Uterine Fibroids (Leiomyomas)

The most common pelvic tumor in women and the leading structural cause of abnormal uterine bleeding. Classification by location predicts the symptom:

Fibroids are estrogen-responsive: they enlarge in pregnancy and regress after menopause. A fibroid that enlarges after menopause, or grows rapidly, warrants evaluation — leiomyosarcoma is rare but this is the presentation that should not be dismissed.

Management ranges from observation for asymptomatic fibroids, through medical therapy for bleeding (tranexamic acid, hormonal contraception, a levonorgestrel intrauterine device for submucosal-sparing anatomy, GnRH modulators), to uterine artery embolization, myomectomy for fertility preservation, and hysterectomy.

Adenomyosis — endometrial glands within the myometrium — causes a diffusely enlarged, boggy, tender uterus with heavy painful periods, and is diagnosed on MRI or ultrasound.

5. Ovarian Cysts

Most cysts in premenopausal women are functional (follicular or corpus luteum) and resolve within one to two cycles. Features that raise concern for malignancy on ultrasound: solid components, thick septations, papillary projections, internal vascularity, ascites and large size.

Postmenopausal cysts require greater scrutiny, since functional cysts should not occur after ovulation ceases.

Ovarian torsion is the emergency: sudden severe unilateral pelvic pain with nausea and vomiting, usually with an ovarian mass over 5 cm. Doppler flow may be preserved because of dual blood supply, so normal Doppler does not exclude torsion, and surgical evaluation is required when clinical suspicion is high.

6. Ectopic Pregnancy

An enumerated blueprint topic and a leading cause of first-trimester maternal death.

The rule that governs the entire topic: every reproductive-age woman with abdominal pain, pelvic pain, syncope or abnormal bleeding gets a pregnancy test before anything else. Ectopic pregnancy has been missed innumerable times because the diagnosis was not considered in a woman who said she could not be pregnant.

Risk factors: prior ectopic pregnancy, prior pelvic inflammatory disease or chlamydial infection, tubal surgery or ligation, infertility and assisted reproduction, intrauterine device in place at the time of conception (which reduces absolute risk of pregnancy but raises the proportion that are ectopic), and smoking.

Presentation: amenorrhea, unilateral pelvic pain and vaginal bleeding — though the classic triad is often incomplete. Rupture presents with severe pain, peritoneal signs, shoulder-tip pain from diaphragmatic irritation by hemoperitoneum, and hemodynamic collapse.

Diagnostic approach:

1. Quantitative beta-human chorionic gonadotropin and transvaginal ultrasound
2. If hCG is above the discriminatory zone and no intrauterine gestation is seen, ectopic pregnancy is presumed
3. If hCG is below the discriminatory zone and the patient is stable, serial hCG measurements are used: a normal intrauterine pregnancy typically shows an appropriate rise over 48 hours, while an inappropriately rising or plateauing level suggests an abnormal pregnancy
4. A pseudogestational sac — a fluid collection in the endometrial cavity — must not be mistaken for an intrauterine pregnancy

Management:

• Unstable, ruptured, or with contraindications to medical therapy: surgery. Laparoscopic salpingostomy or salpingectomy.
• Stable, unruptured, low hCG, small mass, no fetal cardiac activity: methotrexate, with follow-up hCG measurements to confirm resolution. Contraindications include hemodynamic instability, immunodeficiency, significant hepatic or renal disease, cytopenias, breastfeeding, and an inability to attend follow-up.
• Rh-negative women require Rh immune globulin.

A patient receiving methotrexate must be told to avoid folic acid supplements, NSAIDs and alcohol, and that transient abdominal pain is expected — although worsening pain requires reevaluation for rupture.

7. Other Early Pregnancy Considerations for the Internist

• Hyperemesis gravidarum — intractable vomiting with weight loss, ketosis and electrolyte derangement. Thiamine must be given before glucose-containing fluids to prevent Wernicke encephalopathy, which has been reported in this setting.
• Urinary tract infection in pregnancy — an enumerated blueprint topic. Unlike in non-pregnant adults, asymptomatic bacteriuria is screened for and treated in pregnancy, because it progresses to pyelonephritis and is associated with preterm birth.
• Nutritional deficiencies — folic acid before conception and through the first trimester; iron; iodine; and vitamin B12 in patients with malabsorption or restrictive diets.
• Venous thromboembolism — pregnancy and the puerperium are prothrombotic; the postpartum period carries the highest risk.
• Medication review — the single most valuable preconception intervention an internist performs is stopping teratogens before conception rather than after a positive test.