Nutritional Markers Can Identify Functional Amenorrhea

Functional hypothalamic amenorrhea (FHA) has been attributed to excessive exercise or psychogenic stress. French researchers recently reported that mild but prolonged dieting, particularly with fat restriction, might interfere with gonadotropin secretion, leading to FHA. Assessing certain nutritional markers can help identify and correct this purely reversible condition, according to Dr. Gilbert Schaison and colleagues (Clin Endocrinology 1999; 50:229).

Twelve women (22 to 35 years of age) with FHA not related to exercise and 12 age- and BMI-matched controls who were menstruating were enrolled in the study. An additional group of 6 women with congenital hypothalamic hypogonadism—representing complete gonadotropin deficiency—were enrolled as a comparison group. Plasma estradiol (E2) and androstenedione levels were measured, and the pulsatile profile of luteinizing hormone (LH) was studied. A gonadotropin-releasing hormone (GNRH) agonist test using Triptorelin® was performed. Dietary intake and body composition were reported and the following nutritional markers were measured: free triiodothyronine (T3), ferritin, retinol-binding protein (RBP), sex hormone-binding globulin (SHBG), insulin-like growth factor 1 (IGF-1), and leptin.

The 12 women with FHA met with a dietitian for nutritional counseling. They were given a diet of 1800 ± 200 kcal/day (30% fat, 20% protein, and 50% carbohydrate), divided into 3 meals and a snack.

Results

In spite of similar BMIs (19.2 among patients with FHA vs. 20.0 in controls), the caloric intake was significantly lower in women with FHA than in lean menstruating control women. Women with FHA had significantly less body fat and greater lean body mass than normal controls. Nine of the 12 women with FHA were unable to follow the recommended diet ( for unspecified “psychological reasons), and remained amenorrheic. The authors noted that it is common for women with FHA to avoid fat calories and/or to increase daily exercise to keep their weight in the low-normal range.

Among the 3 women who did increase their caloric intake for 4 months, uterine bleeding occurred spontaneously after 2 months.

Changes in markers may uncover abnormal eating patterns

With women who have a BMI in the low-normal range who aren’t exercising excessively, it may be difficult to recognize that lack of nutrition may be causing hypothalamic dysfunction. According to the authors, a reduction in the mean levels of the nutritional markers FT3, ferritin, RBP, IGF-1, and SBGH may provide clues to abnormal attitudes toward food, including severe caloric and fat restriction. In addition, a reduction in plasma leptin levels was consistently noted.

GNRH secretion is partial and reversible when patients with FHA follow a proper diet for several months. In addition, the authors believe that Triptorelin stimulation may be a useful tool for diagnosing occult FHA. Less than 24 hours after it is given, it induces both the release of and then the synthesis of LH, FSH, and E2, demonstrating that the gonadotropin deficiency is functional and thus reversible.