Augmentation of Bone Mineral Density in Hirsute Women
ABSTRACT & COMMENTARY
Synopsis: Hyperandrogenism counteracted the osteopenic effects of relative hypoestrogenism associated with oligomenorrhea.
Source: Dagogo-Jack S, et al. J Clin Endocrinol Metab 1997;82:2821-2825.
The present study asks whether increases in androgen levels or in androgen action as evidenced by hirsutism have a trophic effect of bone mass. In this study, women of similar ethnic heritage were categorized into one of three groups: 1) those with no evidence of hirsutism or hyperandrogenism and regular menses, n = 21; 2) those with evidence of hyperandrogenism and regular menses, n =11; and (3) those with hyperandrogenism and oligomenorrhea, n = 25. Dagogo-Jack and associates classified all of the subjects as Kuwaiti Arabs. Androstenedione, testosterone, SHBG, vitamin D, and intact PTH levels were determined in all subjects. In the hirsute women, androstenedione levels were higher, SHBG levels were lower, and testosterone levels were similar to the control women. Total body and lumber spinal bone density was determined by dual energy x-ray absorptiometry. Total body bone density was much higher in both groups of hirsute women when compared to control women, and lumbar spine bone density was marginally higher in both groups of hirsute women. The subset of women with hirsutism and oligomenorrhea had bone densities intermediate between control women and hirsute women with regular menses. The authors conclude that increased androgen sensitivity of the skin as evidenced by hirsutism probably extends to the extracutaneous skeletal sites that express androgen receptors.
COMMENT BY SARAH L. BERGA, MD
Androgens are known to increase osteoblastic activity, and estrogens decrease osteoblastic activity; thus, one would predict that women with regular menses and hirsutism would have higher bone density than women with regular menses and no evidence of hyperandrogenism. What happens to bone mass when androgens are increased but estrogen exposure is decreased? Previous investigators have suggested that women with polycystic ovary syndrome have estrogen levels that are about 40% lower than those of eumenorrheic women. The present study shows that women with elevated androgens, regardless of menstrual status, have greater bone mass than eumenorrheic women without elevated androgens. Previous studies have yielded similar conclusions. This is not surprising when one considers that androgens can be metabolized in situ to estrogens. Even in men, epiphyseal closure is regulated by estrogen and not androgen receptors (Smith EP, et al. N Engl J Med 1994;331:1056-1061).
What happens when hirsute women present for treatment wishing to have their hirsutism ameliorated? Will suppression of androgens for this purpose cause reduced bone accretion? The apparent answer derived from other studies is possibly. For instance, spironolactone treatment led to reduced bone mineral density in eumenorrheic, hirsute women (Prezelj J, Kocijancic A. Horm Metab Res 1994;26:46-48). On the other hand, studies suggest that the use of oral contraceptives, which confer higher estrogen levels and contain relatively androgenic progestins, produce greater bone accretion than remaining eumennorrheic. There are no studies looking at the relative effect upon bone mass of oral contraceptives alone vs. oral contraceptives plus spironolactone, which is a common therapeutic strategy for the treatment of hirsutism in women with and without oligomenorrhea. Given the above considerations and until better data are available, it seems prudent to use oral contraceptive therapy as the first line of defense in the treatment of hirsutism, reserving the addition of anti-androgens to those who do not adequately respond. It also seems reasonable to avoid the use of anti-androgens aloneparticularly in women with oligomenorrhea, in whom estrogen exposure is already lower.
Which of the following statements is true?
a. Oligomenorrheic women invariably have lower bone mass than eumenorrheic women.
b. Androgens regulate osteoblastic action, and estrogens modulate osteoblastic activity in men and women.
c. Oral contraceptive therapy is a good treatment for oligomenorrheic hirsute women, because it will reduce androgens, spare bone mass, and protect the endometrium from hyperplasia.
d. Across a given interval of time, oligomenorrheic women with polycystic ovary syndrome have higher estrogen levels than eumenorrheic women.
e. It is safe to assume that, regardless of ethnic origin, oligomenorrhea unaccompanied by hirsutism heralds low bone mass.
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