Clinical Review

HRT: 4 experts chart a new course

To clarify the issues raised by the Women’s Health Initiative, OBG Management asked 4 experts the inevitable: Now what? Here, the physicians discuss the findings and detail how this will affect the way they—and you—treat menopausal women.



Our expert commentators
Lorraine Fitzpatrick, MD, is professor of endocrinology and medicine and director of the Women’s Health Fellowship, Mayo Hospital and Mayo Foundation, Rochester, Minn.
Andrew M. Kaunitz, MD, is professor and assistant chair in the department of OBG at the University of Florida Health Science Center in Jacksonville. He also serves as coprincipal investigator at the University of Florida’s Jacksonville site of the Women’s Health Initiative.

Anthony Luciano, MD, is director of the Center for Fertility and Women’s Health, New Britain General Hospital, New Britain, Conn.
John F. Randolph, Jr., MD, is associate professor and director, division of reproductive endocrinology and infertility, department of OBG, University of Michigan Health System, Ann Arbor, Mich.
  • Bisphosphonates and calcitonin, in conjunction with calcium and vitamin D, are as effective as HRT in reducing fragility fractures. Raloxifene also reduces fracture risk.
  • Clonidine hydrochloride, a centrally acting antihypertensive agent, has been used successfully as a viable alternative to HRT in the management of vasomotor symptoms.
  • Women using HRT for vasomotor symptom relief will benefit from periodic assessment—with guidance from their Ob/Gyn—of the pros and cons of continuing the therapy.

Choosing whether or not to begin hormone replacement therapy (HRT) is among the most important health decisions menopausal women face. For years, though, physicians have had to guide their patients through the uncertain waters of HRT with only the help of sometimes conflicting, often inconclusive data. But now a new report offers hard-and-fast evidence to aid in this decision-making process.

In July, the estrogen-progestin arm of the Women’s Health Initiative (WHI)—a large-scale, randomized, controlled clinical trial involving 16,608 women—was halted after researchers concluded that the therapy’s risks outweighed its benefits. For this portion of the study, the subjects (all aged 50 to 79 and all with an intact uterus) received either placebo or a combination of 0.625 mg conjugated equine estrogens (CEE) and 2.5 mg medroxy-progesterone acetate (MPA) daily.1

Researchers found that women assigned to the combined HRT regimen were at greater risk for stroke, heart attack, blood clots, and invasive breast cancer than those in the placebo group. Specifically, for every 10,000 women taking HRT for 1 year, there were 7 more coronary heart disease (CHD) events than among women taking placebo. There also were 8 additional strokes, 8 more cases of breast cancer, and 18 more incidents of pulmonary embolism (PE).

The study also confirmed some beneficial effects: For every 10,000 woman-years of HRT use, there were 5 fewer hip fractures and 6 fewer cases of colorectal cancer.1

Clearly, the increased risk of breast cancer and cardiovascular disease in the estrogen-progestin arm of the WHI study is small. Still, more than 6 million US women currently take this therapy, and they undoubtedly will be seeking answers, alternatives, and assurances. As a result, Ob/Gyns now must reassess the standard HRT regimens and tailor their recommendations to each woman’s medical history (see “Managing menopause: a patient history”) and personal preferences.

Here, 4 experts offer their advice on interpreting the WHI findings and individualizing treatment protocols to offer preventive and therapeutic alternatives.

HRT: Still an option?

OBG Management: In light of the WHI findings, are there patients who would still benefit from taking HRT?

Kaunitz: It is still the most effective therapy for vasomotor symptoms and related sleep, mood, and memory disorders. I continue to recommend HRT or estrogen replacement therapy (ERT) for these symptoms. The WHI findings of an increased risk of myocardial infarction (MI), stroke, and thromboembolic disease in HRT users do not apply to hysterectomized women using or contemplating ERT. Nor do they apply to young surgically castrated women, who will continue to benefit from ERT as well as, in some cases, estrogen-androgen therapy.

Randolph: It is important to inform patients that HRT is a complex medication that acts on many parts of the body and has incompletely understood long-term effects. The primary indications for HRT have not changed: relief of vasomotor symptoms, sleep disturbances, and urogenital atrophy. Women seeking a strategy to reduce osteoporosis or colon cancer risks may also be candidates for HRT.

Luciano: For the majority of peri- and post-menopausal women with significant vasomotor symptoms and vaginal dryness, HRT will continue to be the most important—if not the only—therapeutic option.

Weighing the alternatives

OBG Management: Are there safe alternatives to HRT? If so, what are they? (TABLE 1)

Kaunitz: The bisphosphonates (alendronate and risedronate), available in weekly formulations, offer menopausal women an effective, safe, and convenient nonhormonal approach to preventing and treating osteoporosis. Also, raloxifene, a selective estrogen receptor modulator (SERM), effectively prevents and treats osteoporosis. However, some women will develop vasomotor symptoms or leg cramps with this medication. Still, raloxifene holds promise for its apparent ability to reduce the risk of breast cancer without causing endometrial proliferation.


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