ASRM Review: Prevention of Bone Loss during Long-Term GnRH Agonist Therapy for Endometriosis

Prevention of Bone Loss during Long-Term GnRH Agonist Therapy for Endometriosis

Title: “A Clinical Trial of Alendronate for Prevention of Bone Loss Associated with Gonadotropin-Releasing Hormone Analogues”
Presentation Authors: 1B. Ripps, 1K. Vangilder, 2M. Welford, 3Z. Mamish
Affiliations:1Department of Obstetrics/Gynecology, University of Florida-Pensacola, 2Sacred Heart Hospital Pharmacy, and 3Department of Medical Endocrinology at Sacred Heart Hospital, Pensacola, FL.

Summary written by Christine Schroeder, Ph.D.

Previous research has demonstrated that GnRH analogues/agonists are an effective treatment for endometriosis and fibroids. However, currently, treatment is normally limited to a six-month duration because of the negative effects that GnRH agonist (GnRH AG) therapy can have on bone mineral density (BMD). In fact, women of reproductive age who undergo GnRH AG therapy often show a loss of as much as 2.3% in BMD, comparable to the loss typically experienced by women in the first several years of menopause. This loss in women of reproductive age is particularly noteworthy, because bone density in women of this age group is still often increasing.

However, because GnRH AG therapy is so useful from an endometriosis standpoint, researchers are trying to find ways to minimize the BMD loss and menopausal symptoms that characterize long-term GnRH AG therapy. This study evaluated the benefit of the drug alendronate in preventing BMD loss. Alendronate is a biphosphonate drug traditionally used to prevent bone loss associated with menopause and osteoporosis.

Participants in the study were 12 premenopausal women who were planning to undergo 6 months of GnRH AG therapy; other patients had been excluded because they smoked, had used GnRH AGs in the previous year, had used steroids in the past or present, or if they had thyroid or autoimmune problems. Patients were randomly assigned to receive either alendronate (the treated group) or a placebo (the control group).

Changes in bone mineral density were assessed via dual energy x-ray absorptiometry (DEXA) at the beginning of GnRH AG therapy and at the end of six months of GnRH AG therapy. BMD was measured in the femur (upper leg) and lumbar (lower back) regions.

After six months of GnRH AG therapy, both the control and treatment groups showed significant BMD decreased in the femur region. However, the loss in the control group (3.4%) was significantly greater than the loss in the treated group (1.2%). In the lumbar region, the treated group showed a 1.3% increase in BMD, compared to a 4.1% loss in the control group.

Note: This paper generated a lot of interesting discussion. One group that seemed to be of particular importance in the discussion was young endometriosis patients (i.e., late teens, early twenties), who may be 10 or more years away from childbearing. Finding a way to control endometriosis in this population without interfering with BMD gain would be an invaluable development for doctors who treat this population. In the course of this discussion, the issue of reproductive toxicity arose – would a treatment like this have long-term implications for fertility independent of the endometriosis? The speaker and the audience concurred that the reproductive toxicity of this regimen was unknown, and that research is needed. 

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