UPDATE ON MENOPAUSE
Here is a roundup of the latest data on vitamin D requirements in women and how the route, timing, and duration of hormone therapy influence its safety and efficacy
IN THIS ARTICLE
Given these important findings, I believe it is now reasonable to counsel women in late perimenopause and early menopause that the use of HT may lower their risk of dementia. How long we should continue to prescribe HT depends on individual variables, including the presence of vasomotor symptoms, the risk of osteoporosis, and concerns about breast cancer.
I encourage women to taper their dosage of HT over time, aiming at complete discontinuation or a low maintenance dosage.
Are SRIs an effective alternative to HT for hot flushes?
Freeman EW, Guthrie K, Caan B, et al. Efficacy of escitalopram for hot flashes in healthy menopausal women: a randomized controlled trial. JAMA. 2011;305(3):267–274.
Interest in nonhormonal management of menopausal vasomotor symptoms continues to run high, although only hormonal therapy has FDA approval for this indication. Many trials of serotonin reuptake inhibitors (SRIs) for the treatment of vasomotor symptoms have focused on breast cancer survivors, many of whom use anti-estrogen agents that increase the prevalence of these symptoms. In contrast, this well-conducted multicenter trial, funded by the National Institutes of Health, enrolled healthy, symptomatic, menopausal women.
In the trial, 205 perimenopausal or postmenopausal women 40 to 62 years old who had at least 28 bothersome or severe episodes of hot flushes and night sweats a week were randomized to 10 mg daily of the SRI escitalopram (Lexapro) or placebo for 8 weeks. Women who did not report a reduction in hot flushes and night sweats of at least 50% at 4 weeks, or a decrease in the severity of these symptoms, were increased to a dosage of 20 mg daily of escitalopram or placebo. The mean baseline frequency of vasomotor symptoms was 9.79.
Within 1 week, women taking the SRI experienced significantly greater improvement than those taking placebo. By 8 weeks, the daily frequency of vasomotor symptoms had diminished by 4.6 hot flushes among women taking the SRI, compared with 3.20 among women taking placebo (P < .01).
Overall, adverse effects were reported by approximately 58% of participants. The pattern of these side effects was similar in the active and placebo treatment arms. No adverse events serious enough to require withdrawal from the study were reported in either arm.
Patient satisfaction with treatment was 70% in the SRI group, compared with 43% among women taking placebo (P < .001).
Although Freeman and colleagues convincingly demonstrate that escitalopram is more effective than placebo, the drug is less effective than HT. I agree with Nelson and coworkers, who, in a meta-analysis of nonhormonal treatments for vasomotor symptoms, concluded: “These therapies may be most useful for highly symptomatic women who cannot take estrogen but are not optimal choices for most women.”6
Unopposed estrogen appears to protect against breast cancer
LaCroix AZ, Chlebowski RT, Manson JE, et al; WHI Investigators. Health outcomes after stopping conjugated equine estrogens among postmenopausal women with prior hysterectomy. A randomized controlled trial. JAMA. 2011;305(13):1305–1314.
The WHI continues to surprise with its findings almost a decade after publication of initial data. In this brand new report from the estrogen-alone arm, postmenopausal, hysterectomized women who were followed for a mean of 10.7 years experienced a reduced risk of breast cancer after a mean of 5.9 years of use of conjugated equine estrogens (CEE).
They experienced no increased or diminished risk of coronary heart disease (CHD), deep venous thrombosis, stroke, hip fracture, colorectal cancer, or total mortality after post-intervention follow-up.
Keep in mind that the women in this arm were instructed to discontinue the study medication at the time the intervention phase was halted because of an increased risk of stroke among CEE users. The elevated risk of stroke attenuated with the longer follow-up.
All ages experienced a reduced risk of breast cancer
Some subgroup analyses from the WHI have found differential effects of HT by age of the user, with younger women experiencing fewer risks and more benefits than those who are more than 10 years past the menopausal transition. In this analysis, all three age groups (50–59 years, 60–69 years, and 70–79 years) of women who used CEE had a reduced risk of breast cancer, compared with placebo users.
Other risks did appear to differ by age. For example, the overall hazard ratio for CHD was 0.59 among CEE users 50 to 59 years old, but it approached unity among the older women.
As new and seemingly conflicting data are published, many clinicians and their menopausal patients may feel confused and frustrated. My perspective: It is becoming clear that age during HT use matters with respect to CHD and dementia, and that estrogen-only HT has a different impact on breast cancer risk than does combination estrogen-progestin HT. When this new information from the WHI is considered in aggregate with earlier WHI reports, as well as with data from the Nurses Health Study, the California Teachers Study, and Kaiser Permanente, we can, with growing confidence, advise our patients that menopausal HT does not increase the risk of fatal CHD and may reduce the risk of dementia when used by younger menopausal women with bothersome symptoms. I would define “younger” here as an age younger than 60 years or within 10 years of the onset of menopause.
In regard to breast cancer, it is now clear that, although estrogen-only HT lowers risk, use of combination estrogen-progestin therapy for more than approximately 5 years modestly elevates risk. Each menopausal woman may use this information to make an individual decision regarding use of HT.
In sum, current evidence allows me to feel comfortable counseling most young menopausal women who have bothersome symptoms that the initiation of HT for symptom relief is a safe and reasonable option.
