The Influence of Estrogen Therapies on Bone Mineral Density in Premenopausal Women with Anorexia Nervosa and Amenorrhea

Abstract

Low bone mineral density is one of the primary risks of chronic amenorrhea, and the effects of potentially long-term menstrual disruption on bone mass are serious concerns for individuals with a past or current anorexia nervosa (AN) diagnosis. As such, estrogen therapies are frequently used to address amenorrhea associated with AN. A systematic review of the literature was conducted to examine the effectiveness of estrogen therapies on bone mineral density in women with amenorrhea. Data regarding the effectiveness of oral contraceptives were of low quality and mixed, with the majority of studies finding no benefit of these treatments on bone mineral density. Hormone replacement therapy findings were also mixed, though promising results were found in a study comparing transdermal administration of physiologic estrogen, delivered in developmentally sensitive incremental doses to placebo controls. Though this study suggests a possible role for estrogen therapies in addressing bone density loss in women with AN, in general, more studies are needed. Clinical drawbacks of using these therapies in the treatment of AN, including the loss of menses resumption as a clinical marker for weight and nutritional rehabilitation, must be considered in the decision to use estrogen therapies, particularly given the uncertain effectiveness of most of these treatments.

Introduction

Anorexia nervosa (AN) is a dangerous condition marked by extreme weight loss and malnutrition. An estimated 1.2 million Americans are afflicted with AN, a group that predominantly comprises adolescent and young adult females. Given that this disorder is so disproportionately diagnosed in premenopausal females, amenorrhea due to AN-related weight loss is a significant concern in the medical management of the disorder. Disrupted menstrual function is a particularly pervasive consequence of AN, with even after full recovery, only 35–86% of patients regaining normal weight status and menstrual function (Herzog et al., 1988, Strober et al., 1997).

As low bone mineral density is one of the primary risks of chronic amenorrhea, the effects of potentially long-term menstrual disruption on bone mass are serious concerns for individuals with a past or current AN diagnosis. Further, given that adolescence is both a time of significant bone mass development, as well as the most common time for AN onset, effects of AN-related amenorrhea can be exponentially deleterious in this population. In fact, after controlling for duration of amenorrhea, women who have a history of adolescent AN have been found to have lower bone mass density in adulthood as compared with women who had adult AN (Biller et al., 1989).

Comparitive studies have further confirmed that patients with AN have significantly lower bone mineral density than normal controls (Rigotti et al., 1984, Ward et al., 1997). On average, approximately 50% of adolescents with AN have bone mass density Z-scores lower than − 1at one site at least (Misra et al., 2004, Misra et al., 2004). Further, AN patients have been found to have a significantly higher rate of bone fractures as compared to the general population (Rigotti, Neer, Skates, Herzog, & Nussbaum, 1991). Some studies estimate that more than 40% of patients with long-term anorexia will have fracturing as a result of their low weight status and related low bone density (Herzog et al., 1993).