BETHESDA, MD. — Now that results from the Women's Health Initiative have shot down hormone therapy as a way to prevent coronary events, dementia, and urinary incontinence in postmenopausal women, the only indication left standing has been relief of menopausal symptoms, especially vasomotor symptoms such as hot flashes.
But even this application is on shaky ground, thanks again to results from the Women's Health Initiative (WHI).
One problem with using estrogen plus progestin, or estrogen alone to manage vasomotor symptoms is that a comprehensive quality-of-life assessment in the WHI showed no clinically significant benefit from hormone therapy, Jennifer Hays, Ph.D., said at a conference on the Women's Health Initiative, sponsored by the Department of Health and Human Services. This result carries the caveat that the WHI hormone study enrolled only women who were willing to accept randomization to placebo, which means that women with the worst symptoms were probably not included.
A second problem is that 56% of women in the WHI who had hot flashes when they started hormone therapy experienced a recurrence 8–12 months after stopping hormone therapy.
The finding that symptoms recurred after hormone therapy stopped is “very important,” said Dr. Hays, a developmental psychologist at Scott & White Hospital in Temple, Tex., and a principal investigator for WHI. “We now talk about treating women with estrogen for a short term, but what happens when women get taken off?”
Despite this drawback, hormone therapy is “clearly still the best treatment for vasomotor symptoms,” commented Dr. Robert Brzyski, an ob.gyn. at the University of Texas Health Science Center, San Antonio, and another WHI principal investigator.
The prevalence of menopausal symptoms when women entered the WHI hormone study was related to age. Among women aged 50–54 years, the most common symptom was hot flashes, reported by about 23% of women. Vaginal dryness, headache, and mood swings were each reported by 10%–15% of women, and joint pain was noted by 20%. The prevalence of all symptoms at entry, except joint pain, was lower with increased age. For example, among women aged 55–59 years, the prevalence of hot flashes was 15%.
After 1 year of treatment with estrogen and progestin, about 85% of women with hot flashes reported that this symptom had significantly improved, compared with about 58% of women in the placebo group, a statistically significant difference. Improvement in vaginal dryness was reported by about 75% of women treated with estrogen plus progestin, compared with about 55% in the placebo group, also a significant difference, Dr. Hays said at the meeting.
But serial surveys that measured health-related quality of life using the RAND 36-Item Health Survey failed to identify any clinically meaningful improvement after 1 or 3 years of estrogen-plus-progestin treatment, compared with placebo. A similar quality-of-life assessment using the RAND 36 failed to show any clinically meaningful improvements in women treated with estrogen only, compared with placebo.
The incidence of menopausal symptoms in women who stop hormone therapy was examined by studying the 9,351 women who were still taking their prescribed estrogen plus progestin or placebo regimen when the treatment phase of this trial was stopped in July 2002.
This group constituted 56% of the participants originally enrolled, and included 4,558 in the hormone arm and 4,793 in the placebo group.
During the first 8–12 months after stopping, hot flashes occurred in 56% of women who had this symptom when they began hormone therapy, compared with a 21% incidence in women who had hot flashes when they entered the placebo arm of the study (JAMA 2005;294:183–93). In women who had hot flashes at any time before entering the WHI study, the symptom occurred after treatment stopped in 22% of women who had been on estrogen plus progestin vs. 4% of women from the placebo group.
The results suggest that hormone therapy only postpones certain menopausal symptoms, and it may eventually make the symptoms worse, said Dr. Hays in an interview.
Several management options are alternatives to hormone therapy for menopausal symptoms, including drugs such as clonidine or selective serotonin reuptake inhibitors, treatment with various supplements or herbal agents, or modified forms of hormone therapy that involve different dosages, duration of treatment, hormone formulations, or routes of administration. But these alternatives are all limited by a lack of information on their safety and efficacy, said Dr. Margery Gass, an ob.gyn. at the University of Cincinnati and a principal investigator for the WHI.