A 45-year-old woman who had two normal pregnancies 15 and 18 years ago presents with the complaint of amenorrhea for 7 months. She expresses the desire to become pregnant again.
After exclusion of pregnancy, which of the following tests is next indicated in the evaluation of this patient’s amenorrhea?
This patient has secondary amenorrhea, which excludes etiologies associated with primary amenorrhea, such as chromosomal abnormalities and congenital Müllerian abnormalities. Pregnancy is the most common cause of amenorrhea in a woman of reproductive age, and this should be assessed first. Other possibilities include chronic endometritis or scarring of the endometrium (Asherman syndrome), hypothyroidism, and ovarian failure. The latter is the most likely diagnosis in a woman at this age. In addition, emotional stress, extreme weight loss, and adrenal cortisol insufficiency can cause secondary amenorrhea. An HSG is part of an infertility workup that may demonstrate Asherman syndrome as a cause of amenorrhea, but it is not indicated until ovarian failure has been excluded. Persistently elevated FSH levels (especially when accompanied by low serum estradiol levels) are diagnostic of ovarian failure.
A 22-year-old woman consults you for treatment of hirsutism. Physical examination demonstrates facial acne, as well as dark, course hair on her upper lip, chin, and midsternum. She has a BMI of 35 kg/m2 . Serum LH level is 35 mIU/mL and FSH is 9 mIU/mL. Androstenedione and testosterone levels are mildly elevated, but serum DHEA-S is normal. The patient does not wish to conceive at this time.
Which of the following single agents is the most appropriate treatment of her condition?
This patient has PCOS, diagnosed by the clinical picture and laboratory values, including abnormally high LH-to-FSH ratio (which should normally be approximately 1:1), elevated androgens, and normal DHEA-S. DHEA-S is a marker of adrenal androgen production; when normal, it essentially excludes adrenal sources of hyperandrogenism. Several medications have been used to treat hirsutism associated with PCOS. Oral contraceptives are the most frequently used agents to treat hirsutism in a patient who does not desire pregnancy. They act by increasing sex hormone binding globulin and suppressing LH-driven ovarian androgen production, thereby reducing levels of free circulating androgen. GnRH agonists suppress ovarian steroid production, but they are expensive, cause bone demineralization, and result in menopausal symptoms by causing a medical menopause. Metformin may be used to treat women with PCOS who want to conceive, as it has been shown to improve ovulation rages in women with a high BMI; however, it has not been shown to improve hirsutism. Spironolactone is an anti-androgen that may be used to treat hirsutism; however, it is rarely selected as first line therapy due to the possibility of adverse effects on a developing male fetus in utero.
The patient returns 3 years later. She discontinued the oral contraceptives 1 year ago because she and her husband wanted to get pregnant. Since that time, her periods have been very unpredictable, usually every 3 to 6 months. She would like your advice about the best way to conceive.
Which of the following is the most appropriate first line therapy to help her conceive?
Clomiphene citrate is first line therapy for anovulatory women, including women with PCOS. Most women with PCOS will ovulate with clomiphene citrate, and approximately 50% will conceive. Intrauterine insemination is not an ideal treatment in a setting where ovulation is unpredictable. Metformin may improve ovulation, and is sometimes used in combination with clomiphene citrate. Clomid had been shown to be superior to metformin alone for ovulation induction. Laparoscopic ovarian drilling is not used as much anymore since there are so many other pharmacologic options to induce ovulation. In vitro fertilization would be considered in patients who failed medical therapy.
A 20-year-old woman with Müllerian agenesis is undergoing laparoscopic appendectomy by a general surgeon. You are consulted intraoperatively because the surgeon sees several lesions in the pelvis suspicious for endometriosis.
You should tell the surgeon which of the following?
Retrograde menstruation is currently believed to be the major cause of endometriosis. Supporting this belief are the following findings: inversion of the uterine cervix into the peritoneal cavity can cause monkeys to develop endometriosis; endometrial tissue is viable outside the uterus; and blood can expel from the ends of the fallopian tubes of some women during menstruation. There is an increased incidence of endometriosis in girls who have genital tract obstructions that prevent the blood flow from exiting the uterus, and increase the incidence of retrograde flow out of the tubes. The fact that endometrial implants can occur in the lung implies that lymphatic or vascular routes of spread of the disease also are possible. Another theory of the etiology of endometriosis entails the conversion of coelomic epithelium into glands resembling those of the endometrium. Endometriosis in men, or in women without Müllerian structures, is an example of this causative mechanism.
A 19-year-old patient presents to your office with primary amenorrhea. She has normal breast and pubic hair development, but the uterus and vagina are absent.
Diagnostic possibilities include which of the following?
Since this patient has other signs of pubertal development that are sex steroid–dependent, we can conclude that some ovarian function is present. This excludes such conditions as gonadal dysgenesis and hypothalamic-pituitary failure as possible causes of her primary amenorrhea. Müllerian defects are the only plausible cause, and the diagnostic evaluation in this patient would be directed toward both confirmation of this diagnosis and establishment of the exact nature of the Müllerian defect. Müllerian agenesis, also known as Mayer-Rokitansky-Küster-Hauser syndrome, presents as amenorrhea with absence of a vagina. The incidence is approximately 1 in 10,000 female births. The karyotype is 46,XX. There is normal development of breasts, sexual hair, ovaries, tubes, and external genitalia. There are associated skeletal (12%) and urinary tract (33%) anomalies. Treatment generally consists of progressive vaginal dilation or creation of an artificial vagina with split-thickness skin grafts (McIndoe procedure). Testicular feminization, or congenital androgen insensitivity syndrome, is an X-linked recessive disorder with a karyotype of 46,XY. These genetic males have a defective androgen receptor and/or downstream signal transduction mechanism (in the genome) such that the androgenic signal does not have its normal tissue-specific effects. This accounts for 10% of all cases of primary amenorrhea. The patient presents with an absent uterus and blind vaginal pouch. However, in these patients, the amount of sexual hair is significantly decreased. Although there is a 25% incidence of malignant tumors in these patients, gonadectomy should be deferred until after full development is obtained. In other patients with a Y chromosome, gonadectomy should be performed as early as possible to prevent masculinization. Patients with gonadal dysgenesis present with lack of secondary sexual characteristics. Patients with Klinefelter syndrome typically have a karyotype of 47, XXY and a male phenotype. Causes of primary amenorrhea, in descending order of frequency, are gonadal dysgenesis, Müllerian agenesis, and testicular feminization. XYY syndrome and Turner syndrome often present with menstrual abnormalities, but these patients have a uterus.
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