TABLE 1
Therapeutic alternatives to HRT
| CARDIOVASCULAR EVENTS | OSTEOPOROSIS | HOT FLUSHES | VAGINAL DRYNESS |
|---|---|---|---|
| Aspirin: Daily use effective in lowering the risk of stroke and heart attack | Bisphosphonates: Effective in preventing and treating osteoporosis; may cause digestive disorders | Estrogen pills and patches: Highly effective and may pose less risk to breast tissue and cardiovascular health than oral HRT | Estrogen pills and patches: Highly effective and may pose less risk to breast tissue and cardiovascular health than oral HRT |
| Statins: Effective in women with high and low cholesterol | Raloxifene: Effective in preventing and treating osteoporosis; may cause hot flushes | SSRI antidepressants: Effective in up to 60% of women | Topical estrogen inserted vaginally: Effective in treating dryness |
| Beta blockers, ACE inhibitors: Reduce risk of heart attack in hypertensive patients | Calcium and vitamin D: Daily intake keeps bones strong and lessens fracture rate | Soy/black cohosh: Conflicting data on its effectiveness | Nonprescription gels and creams: Offer temporary relief of dryness, as well as pain and itching |
| ACE = angiotensin-converting enzyme; HRT = hormone replacement therapy; SSRI = selective serotonin reuptake inhibitor | |||
Duration of therapy
OBG Management: Since there was no difference in breast cancer rates during the first 4 years of the WHI study between women taking estrogen plus progestin and those taking placebo, do you recommend that some women take HRT for less than or up to 5 years?
Kaunitz: For many women, fewer than 5 years of HRT will be sufficient for relief of symptoms. Clinicians are well aware, however, that some menopausal women remain symptomatic (without treatment) for far more than 5 years.
In this latter group, is it safe to continue HRT longer than 5 years? Ob/Gyns and their patients should recognize that the increased risk of breast cancer noted in estrogen-progestin users in the WHI study is small (RR 1.26) and only marginally achieved statistical significance (95% confidence interval [CI], 1.00-1.59). To appropriately guide clinical decisions, this relative risk needs to be translated into an attributable/absolute risk. For example, as was pointed out earlier, for every 10,000 women taking HRT for 1 year, we would anticipate 8 additional cases of breast cancer. Another way of stating this is that among 100 women using HRT for 10 years, 1 woman would be diagnosed with breast cancer.
We also need to recognize that the WHI data observed no abrupt increase in breast cancer diagnosis after 4 years of HRT use. Rather, the risk of breast cancer rose slowly over time. This difference achieved statistical significance after an average of more than 5 years of use. Thus, women using HRT for symptom relief will benefit from periodic assessment—with guidance from their Ob/Gyn—of the pros and cons of continuing the therapy. In some, the most educated decision can be made only after the patient has tapered off and then discontinued HRT. If symptoms recur, many women may choose to restart HRT.
Luciano: While the risk of breast cancer does not appear to increase during the first 4 years of HRT use, cardiovascular events are increased from the first year and beyond.
Randolph: It would be naive to think that any cancer-promoting action of HRT occurs only after a certain time threshold. Biologically, it is most plausible that any effect is small but cumulative—just not apparent until after several years. Therefore, it would be most appropriate to use HRT for specific indications and for the shortest time possible. If symptoms persist and are intolerable without HRT, we need to counsel patients about the relatively small but cumulative risk of continuing the therapy. It is ultimately their decision, but it is our responsibility to inform them adequately.
Fitzpatrick: It is important to note the differences in the nominal and adjusted confidence intervals. For example, if you look at the adjusted CIs, the increase in breast cancer is not statistically significant. However, there is statistical significance on the nominal CIs. For this reason, it is still difficult to make a judgment call about the length of time to use HRT. Certainly, patients should be informed of the possibility of an increased risk so that a joint decision can be made between the patient and her care provider. If there are other compelling reasons to continue the estrogen, an informed, individualized decision can be made.
Lower-dose HRT regimens
OBG Management: Some authorities recommend taking lower doses of estrogen plus progestin. Could you describe HRT’s mechanism of action and explain how lower-dose regimens would differ from the HRT administered in the study?
Case studies from our panel
A 55-year-old woman initiated combination hormone replacement therapy (HRT) 3 years ago for the relief of vasomotor symptoms. Since then, her hot flushes and irritability have resolved, and sleeping patterns have improved. In addition, memory lapses (including word-finding difficulties at work) have improved, seemingly as a consequence of HRT. Results of a dual-energy x-ray absorptiometry (DEXA) bone mineral density (BMD) study of the lumbar spine and femur are normal. After this patient and I review the Women’s Health Initiative (WHI) findings, she opts to try discontinuing HRT. I instruct her to take her combination HRT tablets every other day for a month, then discontinue them completely. I also encourage her to schedule a follow-up office visit 2 months after discontinuing the regimen. If she is feeling well at that time, without bothersome vasomotor symptoms, our tentative plan is for her to remain off HRT and have her bone density rechecked in several years. If symptoms recur once she discontinues HRT, the patient likely will choose to restart HRT. She has been counseled that no alternative medication treats these symptoms as effectively as HRT.
A 62-year-old woman started combination HRT 4 years ago when she was diagnosed with spinal osteoporosis. This slender woman had smoked 1 pack of cigarettes daily from her 20s to her early 50s. At the time of her initial BMD study, her spinal T score was -2.8 and her total femur T score was -1.9. A follow-up BMD study 2 years after starting HRT showed a 4% to 5% increase in spinal BMD and a stable femur BMD. During a recent annual gynecologic exam, the patient and I discussed alternative osteoporosis treatments. She chose to taper off her combination HRT and start a weekly bisphosphonate regimen (alendronate 70 mg or risedronate 35 mg weekly tablets). If she notes vaginal dryness or discomfort associated with genital atrophic changes, she likely will start local vaginal estrogen treatment.—ANDREW M. KAUNITZ, MD