Gain knowledge from NAMS on life after hormone therapy

The following Q & A article summarizes a discussion in Menopause e-Consult, a newsletter of the North American Menopause Society (NAMS).

When to consider prophylactic bisphosphonate

In light of the risk of rapid bone loss after a woman discontinues hormone therapy (HT), should we recommend prophylaxis with a bisphosphonate for postmenopausal women once they stop HT? ¹

The evidence. The effect of HT on reducing bone loss and preventing osteoporotic fractures in postmenopausal women has been well established by both randomized, controlled trials (RCTs) (the Postmenopausal Estrogen/Progestin Inter-ventions and Women's Health Initiative) and observational studies (the National Osteoporosis Risk Assessment [NORA] and Million Women Study).^2-5 However, many studies have shown that women can lose 3% to 6% of their bone mineral density (BMD) during the first year after stopping HT-a phenomenon often called catch-up bone loss-and that protection from fracture doesn't persist.^6-9

Data from NORA, a longitudinal cohort study of women who used HT, showed that women who had stopped therapy more than 5 years before had BMDs similar to never-treated women.¹⁰ Another analysis of NORA data found a 40% decrease in hip fractures among current HT users, but no protective effect among past users.¹¹

Notably, women who had stopped HT within the past 5 years had almost 70% more hip fractures than women on therapy did, suggesting that the accelerated bone loss that occurs when a women stops HT increases her risk of fractures. Estrogen withdrawal seems to stimulate release of bone-resorbing cytokines, such as tumor necrosis factor and interleukin-1.¹²

An analysis of the skeletal consequences of stopping HT reviewed 11 RCTs that tracked changes in BMD during and after therapy, including five studies that reported data on bone turnover markers.¹³ During the first year after discontinuing HT, mean spinal BMD decreased by 2.3% to 6.2%, and bone turnover markers increased rapidly. The degree of bone loss wasn't affected by mean age, use of HT to prevent or treat osteoporosis, or duration of treatment (1 to 5 years).

Trials of treatment options. Two of the RCTs evaluated therapies to protect bone. The larger study randomized 144 postmenopausal women who had low bone mass within 3 months of stopping HT to either 10 mg per day of alendronate or placebo.¹² The alendronate group showed a 5.5% greater lumbar spine BMD, greater hip and total body BMD, and significantly lower bone turnover markers than the placebo group did.

The smaller trial, a 3-year study of 23 women with breast cancer who had stopped HT and undergone standard surgical treatment, compared a selective estrogen-receptor modulator (SERM; toremifene or tamoxifen) plus clodronate with a SERM plus placebo.¹⁴ The SERM/clodronate group remained stable; the SERM/placebo group showed significant spinal bone loss.

Post-HT evaluation. Women who discontinue HT should have a posttherapy baseline dual energy x-ray absorptiometry and complete re-evaluation of clinical risk factors for osteoporosis. The World Health Organization's new Fracture Risk Assessment Tool (FRAX) can reasonably be used to assess 10-year fracture risk^15,16 and guide recommendations, although it was developed for patients who haven't received HT.

Who should take a bisphosphonate? The 2008 National Osteoporosis Foundation guidelines offer direction.¹⁷ Patients can be grouped into three categories:

RISA KAGAN, MD, FACOG, CCD, NCMP, IS CLINICAL PROFESSOR, DEPARTMENT OF OBSTETRICS, GYNECOLOGY, AND REPRODUCTIVE SCIENCES AT THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO; EAST BAY PHYSICIANS MEDICAL GROUP, BERKELEY, CA; MEMBER, NAMS BOARD OF TRUSTEES.

DISCLOSURE: Dr. Kagan reports: Consultant/advisory board-Aventis, Depomed, Eli Lilly, FORE-American Bone Health, Medtronic, Procter & Gamble, Wyeth; grants/research support-Boehringer Ingelheim, Depomed, Eli Lilly, Novartis, Procter & Gamble; speakers bureau-Eli Lilly, GlaxoSmithKline, Novartis, Novogyne.

(Disclaimer: The opinions expressed in the newsletter and summarized in Contemporary OB/GYN are those of the authors and are not necessarily endorsed by NAMS.)