Amenorrhea

D. Melessa Phillips and Susan D. Andrews

I. Primary amenorrhea is (1) the lack of menses by age 14 and the absence of secondary sexual characteristics or (2) the lack of menses by age 16 regardless of the presence or absence of breast development or axillary and pubic hair. Secondary amenorrhea is the lack of menses in a previously menstruating woman for (1) 6 months or (2) the equivalent of her 3 previous cycle intervals. II. Diagnosis. Regardless of the patients age, parity, or contraceptive status, pregnancy must be ruled out in each case. A. History. Key questions to ask the patient are the following: 1. Is there a family history of delayed menarche or premature menopause? 2. What are your current diet and exercise habits? Have you had recent weight loss or gain? Do you experience symptoms of anorexia or bulimia? 3. Do you have headaches, visual changes, or galactorrhea? 4. Do you have any signs or symptoms of pregnancy? 5. Do you have hot flashes, vaginal dryness, or painful intercourse? 6. Have there been recent significant stressful life events? 7. What medications are you taking? 8. Do you have fatigue, hair loss, hirsutism, or acne? 9. Is there a history of radiation or chemotherapy? 10. Is there a history of postpartum hemorrhage, dilation and curettage, or infertility? B. Physical examination 1. General. Look for signs of acromegaly, Turners syndrome, and Cushings disease. 2. Head, eye, ear, nose, and throat. Look for excessive facial hair, acne, papilledema, and cranial nerve or visual field defects. 3. Neck. Look for goiter and thyroid nodules. 4. Breasts. Look for tenderness, galactorrhea, axillary hair, and breast development. 5. Pelvic. Look for pubic hair, imperforate hymen, vaginal or uterine agenesis, ambiguous genitalia, pseudohermaphroditism, polycystic ovaries, and cervical stenosis. C. Workup (see Fig. 16-1)

Figure 16-1. Workup of amenorrhea. (TSH = thyroid-stimulating hormone; FSH = follicle-stimulating hormone; LH = luteinizing hormone.) 1. Progesterone challenge test (PCT). The PCT evaluates (a) the competency of the outflow tract and (b) the patients level of endogenous estrogen. Give medroxyprogesterone acetate (MPA), 5 mg orally daily for 5 consecutive days. A positive test result consists of any amount of vaginal bleeding within 27 days after the fifth tablet and confirms the diagnosis of anovulation. The combination of a positive PCT result, normal serum prolactin, and no history of galactorrhea essentially rules out a significant pituitary tumor (1). 2. Cyclic estrogen and progesterone regimen. Administer 1.25 mg conjugated estrogen per day orally for 21 days, adding 10 mg of MPA on days 1621. If no withdrawal bleed occurs by day 28, a second cycle of combined estrogen and progesterone regimen is recommended. A second negative response means that the etiology of the amenorrhea is in either the endometrium or outflow tract; these patients should be referred to a gynecologist for definitive studies. A positive response indicates that the patient is capable of menstruating if adequate stimulatory estrogen levels are available. III. Management A. Anovulation. If a patient does not desire pregnancy, anovulation may be treated with any lowestrogen dose oral contraceptive pill given in the usual manner. If the patient does desire pregnancy, 10 mg of oral MPA can be administered daily on calendar days 110 of each month for 36 months. If a woman fails to bleed at any time on any progesterone treatment regimen, the sequence for a negative PCT result (see Fig. 16-1) must be instituted. B. Positive response to cyclic estrogen or progesterone regimen. A withdrawal bleed after a cycle of combined estrogen-progesterone indicates measurement of serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels to determine if (a) gonadotropin levels are adequate or (b) an ovarian follicular defect is present. Elevated levels of FSH and LH are diagnostic of ovarian failure and, in the nonmenopausal woman, should be investigated with tests of serum calcium, phosphorus, morning cortisol, thyroxine, thyroid-stimulating hormone, thyroid antibodies, CBC, erythrocyte sedimentation rate, total protein, rheumatoid factor, and antinuclear antibody to rule out systemic causes of premature ovarian failure. Patients with normal FSH and LH levels and a negative PCT result must be investigated for pituitary or central nervous system etiologies. If the FSH and LH are low, MRI of the sella turcica is necessary to rule out a nonfunctioning or prolactinsecreting pituitary tumor. If an adenoma is found, refer the patient for neurosurgical evaluation or medical treatment with bromocriptine. For accuracy, measure FSH and LH levels at least 2 weeks after giving the

combined regimen (exogenous estrogen can affect endogenous gonadotropin levels). IV. Treatment. Women with gonadal failure or hypothalamic amenorrhea should be treated with hormones to lower their risk of osteoporosis and coronary artery disease. Dosage of 0.625 mg of conjugated estrogen on calendar days 125 and 10 mg of MPA on days 1625 induces menstruation in most patients; occasionally 1.25 mg of estrogen is required. Women who do not want to have menstrual periods on hormonal replacement therapy can be given a combination of 0.625 mg of conjugated estrogens and 2.5 mg of MPA every calendar day (now available as Prempro in 0.625-mg and 1.25-mg estrogen strengths). With careful monitoring, combination oral contraceptives can be used in women without risk factors until age 50.