To the Editor:  

Quality of life is an important consideration when evaluating treatment options to prevent osteoporosis-related fractures in postmenopausal women. The benefit-risk ratio of treatment varies for women, depending on age and severity of menopause-related symptoms. 

The October 2008 review article by M. Jill Gronholz, DO,¹ provides valuable information on the use of a multifactoral approach in the management of osteoporosis-related fractures. 

Unfortunately, Dr Gronholz¹ seems to dismiss the role of hormone replacement therapy (HRT) as a viable mode of treatment for this population. The following single reference was made in regard to HRT: “Although hormone replacement therapy has long been an option for osteoporosis prevention, recent findings from the Women's Health Initiative [WHI]^2,3 resulted in new recommendations to limit its prophylactic use.”¹ 

It is true that the WHI results indicated significantly increased risks of cardiovascular events and breast cancer for women taking estrogen and progestin therapy. However, level 1a evidence continues to support the use of HRT for risk reduction of osteoporosis-related fractures based on an individual's history, risk factors, and need for treatment of vasomotor symptoms.⁴ 

Results of the WHI showed that the use of conjugated equine estrogen (CEE, 0.625 mg daily) together with medroxyprogesterone acetate (MPA, 2.5 mg daily) reduced the risk of hip and clinical vertebral fractures by 34%, and the overall risk of fractures by 24%, compared with placebo.⁵ (These percentages are calculated from the associated hazard ratios reported in the study.⁵) This risk reduction amounted to five fewer hip fractures per 10,000 women per year.⁵ 

In regard to cardiovascular risk, recent data have revealed an important therapeutic window of opportunity for HRT implementation. In the WHI estrogen-plus-progestin arm,⁶ coronary heart disease (CHD) relative risk results—in terms of hazard ratio (HR) and according to time since menopause—were the following (P for interaction=.33): 

In the WHI estrogen-only arm,⁷ the relative risks of CHD death—according to age at randomization—were the following: 

Thus, recent WHI results^5-7 suggest that HRT may decrease coronary disease in younger women (ie, those near the age of menopause), but it may increase the risk of a coronary event in older women. 

Differences in age at HRT initiation and duration of therapy are relevant factors in treatment outcomes. These WHI results^5-7 should modify the benefit-risk perception of HRT and support an individualized approach to management. 

In another recent update, WHI investigators reported outcomes in patients 3 years after study medication (ie, estrogen-plus-progestin or placebo) was halted.⁸ No increased risk for thrombosis, CHD, or stroke was observed during these subsequent 3 years in women who had received HRT. Moreover, a statistically significant increased risk for invasive breast cancer, associated with HRT, did not persist at 3-year follow-up.⁸ It is also important to note that in the estrogen-only arm of the WHI study,^2,7 no increased absolute risk of breast cancer was observed during 6.8-year follow-up. 

The effectiveness of low-dose HRT (CEE, 0.3 or 0.45 mg daily, combined with MPA, 1.5 or 2.5 mg daily) has been demonstrated for the treatment of patients with vasomotor symptoms or genital atrophy, as well as for the prevention of bone loss, with fewer adverse effects than standard-dose HRT.^9,10 These initial results were confirmed by the HOPE (Women's Health, Osteoporosis, Progestin, Estrogen) study.¹¹ Further research, however, is needed to determine the clinical effects of low-dose HRT on fracture, cardiovascular disease, and breast cancer. 

The review article by Dr Gronholz¹ mentions only briefly the use of selective estrogen receptor modulators as a treatment or prevention option. Yet, when compared with placebo, raloxifene hydrochloride—approved by the US Food and Drug Administration for the prevention of osteoporosis¹²—has been shown to decrease bone resorption, increase bone mineral density, and reduce fracture risk by 35% to 50% in women with osteoporosis (P<.001).¹³ 

The North American Menopause Society's position statement¹⁴ concludes that recent data support the initiation of HRT at menopause to manage vasomotor symptoms and to reduce the risk of osteoporosis in select postmenopausal women. As noted in the WHI results,^5-7 the benefit-risk ratio for HRT is favorable when treatment begins close to menopause, but this benefit-risk ratio decreases with age and with time since menopause. 

These findings should have been emphasized in the review article by Dr Gronholz.¹ Furthermore, we, as osteopathic physicians, should consider these findings when making informed treatment recommendations to our patients—especially because our profession emphasizes a holistic approach to patient care. 

In summary, recent data argue for the need to balance the benefits of HRT against its potential risks. Recommendations for individualized regimens and dosing of HRT need to be based on severity of symptoms—choosing the lowest appropriate dose for the shortest duration of time—as well as time since menopause.