Severity of Osteopenia in Estrogen-Deficient Women with Anorexia Nervosa
September 1, 1999 4 minutes read
Severity of Osteopenia in Estrogen-Deficient Women with Anorexia Nervosa and Hypothalmic Amenorrhea
Abstract & Commentary
Synopsis: Women with anorexia nervosa had lower bone density of the lumbar spine and hip than women with functional hypothalamic amenorrhea, despite the presence of comparable duration of amenorrhea in both groups. Both women with AN and FHA had lower bone density than eumenorrheic women.
Source: Grinspoon S, et al. J Clin Endocrinol Metab 1999;84:2049-2055.
Grinspoon and associates undertook the present study to determine if factors other than estrogen deficiency contribute significantly to the osteopenia seen in amenorrheic women. To do this, they compared bone densities and other biochemical parameters in women with anorexia nervosa (AN) whose amenorrhea is due largely to undernutrition to those with amenorrhea and normal body weight, i.e., women with functional hypothalmic amenorrhea (FHA). A control group of eumenorrheic women was included. A total of 79 women were enrolled. Nineteen had FHA, 30 had AN, and 30 were eumenorrheic. Women with FHA were between 90 to 110% of ideal body weight, whereas those with AN weighed less than 85%. Physical activity was comparable in FHA and AN. Total calcium and vitamin D intakes did not differ between the three groups. Lifetime duration of amenorrhea, age of menarche, estradiol level, testosterone level, and prior use of estrogen also did not differ between the AN and FHA groups. Body mass index, lean body mass, calorie intake, fat intake, and IGF-I were lower in AN compared to FHA and control women. Bone density was lowest in AN and highest in the controls. At the lumbar spine, 40% of AN and 16% of FHA demonstrated spinal bone density more than 2.0 SD below the expected outcome. Likewise, at the hip, 40% of AN and only 5% of FHA had bone density more than 2.0 SD below the expected outcome.
Comment by Sarah L. Berga, MD
Bone accretion in women depends on several factors, including estrogen exposure, adequate calcium and mineral intake, sufficient vitamin D exposure, appropriate amounts of exercise, and overall good nutrition. Excess cortisol blocks and androgens increase osteoblastic activity. Osteoblasts build bone, so too much cortisol of either endogenous or exogenous origin can prevent bone formation. In contrast, estrogens decrease osteoclast activity, thereby slowing bone resorption. Bone accrues when osteoblast activity exceeds that of the osteoclasts. One might think that women with anorexia nervosa, who are thought to have cortisol levels much higher than those of women with "garden variety" FHA would have lower bone mass than women with FHA because of reduced osteoblastic activity. This study shows that women with AN do indeed have lower bone mass, but not because they have higher cortisol levels. Interestingly, women with FHA had elevated 24-h urinary free cortisol levels more often (50%) than women with AN (30%). Rather than having decreased osteoblastic activity and decreased bone formation, women with AN had lower bone mass largely due to increased bone resorption. This differentially increased bone resorption seen in AN and less so in FHA was attributed not to differences in estrogen exposure but, rather, the impact of undernutrition. The important take-home point, and one not mentioned by Grinspoon et al, is that this biochemical picture suggests that women with AN might respond better to bisphosphonates or exogenously given sex steroids, which slow bone resorption, than women with FHA.
This paper raises a related point. I have often been asked if FHA is not just a milder version of AN. Certainly, in some aspects, FHA and AN are similar. Both are accompanied by amenorrhea due to decreased GnRH drive. But this paper supports the view that they are different in some important ways. One is that the genesis of the disorders differs. Women with AN eat significantly less and weigh significantly less than women with FHA. The primary cause of AN is undernutrition and a distorted body image that creates a huge drive for thinness. Women with FHA may lose weight and not eat properly, but they do not starve themselves to the same extent. Our research supports the notion that women with FHA are stressed rather than seriously undernourished. This contention is supported by the somewhat higher cortisol levels observed in FHA as compared to AN in this study. Further, in my experience, women with FHA do not later become anorectics. This is not to say that anorectics are not sometimes misdiagnosed as having "garden variety" FHA. Because the genesis of AN and FHA differ, both the sequelae and treatment differ too. While anorexia is much less common (about 1% of reproductive-age women) than FHA (5-15% of reproductive-age women), only AN carries a risk of death. While it is important to recognize both disorders, if the diagnosis is felt to be AN, it is imperative that prompt psychiatric consultation be instituted. Women with FHA, on the other hand, have a good chance of recovering ovulatory function if a compassionate clinician can guide them in the art of stress management and a healthier lifestyle.
Which variable differs most between women with anorexia nervosa and those with functional hypothalamic amenorrhea?
a. Extent of ovarian quiescence
b. Exercise quotient
c. Calcium and vitamin D intake
d. Extent of undernutrition
e. Testosterone levels
You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content