Androgens Significantly Reduced in Anorexic vs Healthy Weight Women

Female patients with anorexia nervosa who do not have regular menstrual cycles suffer from decreased levels of androgens, which is exacerbated by the use of oral contraceptives, according to research presented at 89th annual meeting of the Endocrine Society.
"Androgens are severely reduced in women with anorexia nervosa who are getting oral contraceptives," said Karen K. Miller, MD, the study's lead investigator, an endocrinologist at Massachusetts General Hospital, and an assistant professor of medicine at Harvard Medical School, in Boston, Massachusetts. "It's important to know this because in the clinical world it can be common for physicians to prescribe oral contraceptives [to] anorexic women because they have amenorrhea."
The prescription of oral contraceptives to young women with anorexia nervosa and amenorrhea has been thought to increase their bone health, because estrogen replacement is beneficial in postmenopausal women, noted Dr. Miller.
"Estrogens are helpful in postmenopausal women," she said, but stressed that 2 published trials found that oral contraceptive use showed no benefit to bone health in anorexic women with amenorrhea.
"The thinking has been that the estrogens may be a good fix or preserve bone [in anorexic women] at a time when women are losing bone," said Dr. Miller.
In a cross-sectional study of 217 subjects, investigators examined endogenous and dehydroepiandrosterone (DHEA) levels in women with anorexia nervosa who are taking oral contraceptives (n = 32), in women with anorexia nervosa who are not taking oral contraceptives (n = 137), in normal-weight women with hypothalamic amenorrhea (n = 21), and in healthy eumenorrheic controls (n = 27).
Investigators measured bone mineral density and body composition using dual energy x-ray absorptiometry. Total testosterone was measured with radioimmunoassay, sex hormone-binding globulin (SHBG) was measured using an immunoradiometric assay, and free testosterone was calculated from total testosterone and SHBG using the laws of mass action.
Several statistically significant results emerged from the study. Comparing women with anorexia nervosa who were not taking oral contraceptives with healthy controls, anorexic patients had reduced levels of total testosterone (20.6 vs 32.3 ng/dL; P < .05) and free testosterone (0.32 vs 0.47 ng/dL; P < .05). However, the difference in DHEA levels between anorexia nervosa subjects on estrogen and healthy controls was not significant (155 vs 176 μg/dL).
Androgens were further reduced with estrogen intake; decreases were more marked in both free testosterone and DHEA levels in anorexic women taking oral contraceptives than in healthy controls (0.13 vs 32.3 ng/dL; P < .05 for free testosterone; 113 vs 176 μg/dL; P < .05 for DHEA level). Women who had normal weight and hypothalamic amenorrhea had normal levels of both androgen and DHEA.
Androgen levels — specifically free testosterone, total testosterone, and DHEA — weakly, but nevertheless significantly, predicted bone mineral density at postanterior and lateral spine, and total hip, radius, and total body, with the exception of DHEA at the total hip. The most robust association was between free testosterone and lateral spine (R, 0.28; P = .005).
In addition, free testosterone was positively associated with fat-free mass (R, 0.19; P = .04).
The findings underline the fact that the "critical therapy" for anorexic patients with amenorrhea is to regain their body weight, said Dr. Miller.
Dr. John Wass, MD, a professor of endocrinology at the University of Oxford, in Oxford, United Kingdom, said the study highlights the fact that estrogen use should be discontinued in anorexic women who have amenorrhea.
"Putting women who have amenorrhea and don't gain weight onto the pill may have a detrimental effect on their bones," said Dr. Wass, who moderated the session in which the study was presented. "It would be intuitive to think estrogen replacement would help these women who have anorexia and are likely to fracture, but this sounds like a bad idea if this might reduce their testosterone levels and have an adverse effect on bones. The most important treatment is for patients to gain weight and thereby improve the health of their bones."