Case Studies

Case 4: Amenorrhea

A 37-year-old G0 presents to your office for her annual visit. For the past 5 years she has noted irregular menses, but now she has not had a period in 7 months and wonders if this is abnormal.

• 1. How is amenorrhea defined?

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  Correct answer: Primary amenorrhea is the absence of menstruation by age 16. This patient is considered to have secondary amenorrhea – defined as cessation of an established menstruation for 3 months in a woman with a history of regular cycles, but now without menses.

• 2. How should this patient be evaluated?

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  Correct answer: The initial priority is to make sure that she is not pregnant. Once that has been ruled out, a detailed history of reproductive events leading up to the occurrence of amenorrhea is obtained. General questions about health and lifestyle may identify a history of systemic illness or any pattern of excessive stress (physical, psychological, or nutritional) that could affect hypothalamic function. A history of past and/or present use of medication – particularly oral contraceptives or other types of hormonal contraception (Depo-Provera) – can be very illuminating.

  The patient’s overall body habitus, height, and weight should be determined. This may reveal very low body weight (decreased percentage of body fat) associated with hypothalamic amenorrhea, or upper body segment obesity (truncal obesity), often associated with insulin resistance and hyperandrogenism. The presence of hirsutism would indicate the possibility of polycystic ovarian syndrome (PCOS), or less likely an adrenal or ovarian androgen-producing tumor if progression is rapid or associated with virilization. A rapid pulse may suggest hyperthyroidism, whereas a slow pulse may indicate the possibility of hypothyroidism. Signs of Graves disease, such as exophthalmos, lid retraction, or tremor would suggest thyroid dysfunction, as would a palpable goiter or other nodule.

  Initially, the simplest panel would be FSH (follicle-stimulating hormone), TSH (thyroid-stimulating hormone), and prolactin.

• 3. Her TSH and prolactin are both normal. The FSH level is not in the menopausal range. What is the next step?

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  Correct answer: This patient does not have evidence for thyroid dysfunction or prolactinoma. She has a normal reproductive tract and either too much unopposed estrogen or not enough. Administration of progestin for a week to induce withdrawal bleeding could be the next step. If she does not have bleeding, then an estrogen/progesterone challenge would be helpful in differentiating between a structural problem (eg, Asherman syndrome) and hypogonadotropic hypogonadism (eg, Sheehan syndrome). A “positive” withdrawal bleed after progestin therapy would suggest PCOS or some type of hypothalamic dysfunction. She appears to have eugonadotropic hypogonadism – most likely to be PCOS. However, to make a more definitive diagnosis, a panel of testosterone, DHEA (dehydroepiandrosterone), and 17-hydroxyprogesterone would be helpful.

• 4. She has a “period” after 7 days of progestin therapy and her examination suggests PCOS. As she is not attempting to get pregnant, what is the best medical therapy to treat anovulation and amenorrhea?

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  Correct answer: Oral contraceptives are very effective agents in the long-term management of PCOS. They break the cycle through suppression of pituitary LH (luteinizing hormone) secretion, suppression of ovarian androgen secretion, and increased production of circulating sex hormone-binding globulin (SHBG). Oral contraceptives are also associated with a reduction in the risk of endometrial cancer. Alternatively, cyclic progestin therapy is an option. Metformin and other insulin-sensitizing agents have been explored, but are currently unproven therapeutic options.

• 5. Does weight loss improve ovarian function in obese women with PCOS?

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  Correct answer: Yes – obesity contributes substantially to reproductive and metabolic abnormalities in women with PCOS. Weight loss can improve the fundamental aspects of the endocrine syndrome by decreasing circulating androgen levels and causing spontaneous resumption of menses. Other benefits include decreased circulating testosterone levels largely mediated through increases in SHBG. In addition, weight loss can result in significant improvement in the risk of diabetes and cardiovascular disease. Lifestyle modification (diet and exercise) should be promoted as the main primary treatment for all obese women with PCOS.