Gain knowledge from NAMS on life after hormone therapy

November 1, 2009

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

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 risk15,16 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.)