Grand Rounds: What's the best approach to spontaneous premature ovarian failure?

November 1, 2004
Lawrence M. Nelson, MD

DR NELSON is a medical officer in the United States Public Health Service, Integrative Reproductive Medicine Unit, Intramural Research Program on Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Dev

Learning that she has what used to be called premature menopause can devastate a woman in her 20s or 30s. Diagnose this mysterious condition without delay, deliver the bad news in person, and provide sensitiveanswers to four basic questions.

Spontaneous POF-the development of amenorrhea, sex hormone deficiency, and elevated serum gonadotropin levels before age 40-affects about 1% of women.1 For the women with this disordered menstrual pattern whom we've seen at the National Institutes of Health (NIH) Clinical Center, the median age of onset is 25 years.2 The term "spontaneous" means that the ovarian failure wasn't induced by chemotherapy, radiation therapy, or surgery. In the majority of cases the disturbance in menstrual regularity is a secondary development, as most of these patients have experienced normal puberty with menarche and the development of secondary sexual characteristics.2,3

Patients often complain about how long it took them to get a diagnosis of POF. Certainly, the first clinical challenge is to diagnose this disorder early on (Table 1).

Do the right tests. Readily available commercial assays make it possible to quantify circulating steroid and protein hormone levels, enabling us to differentiate patients with amenorrhea into distinct etiologic categories. In 1990 Rebar and Connolly recommended laboratory evaluation for all women with amenorrhea to identify women with spontaneous POF or other types of amenorrhea.3 Although a complete discussion about the differential diagnosis of secondary amenorrhea is beyond the scope of this review, a careful history and physical examination can lead to an appropriately targeted evaluation.4