Menopause Live (9 August, 2010) from IMS 

Although most women in the estrogen-alone (conjugated equine estrogen, CEE) arm of the Women’s Health Initiative (WHI) did not suffer vasomotor symptoms, the newly published study [1] followed those women (n = 3496) during the active phase and then after discontinuation of trial medication at a mean 7.4 ± 1.1 years from baseline. The mean age at trial closure was 73 years. Approximately one-third of participants reported at least one moderate to severe symptom at baseline. Fewer symptoms were reported with increasing age, except joint pain/stiffness, which was similar among age groups. At 1 year, hot flushes, night sweats and vaginal dryness were reduced by CEE, whereas breast tenderness was increased. Breast tenderness was also significantly higher in the CEE group at trial closure. After stopping, vasomotor symptoms were reported by significantly more women who had reported symptoms at baseline, compared with those who had not, and by significantly more participants assigned to CEE (9.8%) vs. placebo (3.2%); however, among women with no moderate or severe symptoms at baseline, more than five times as many reported hot flushes after stopping CEE (7.2%) vs. placebo (1.5%). The concluding sentences of the article’s Abstract were as follows: ‘CEE significantly reduced vasomotor symptoms and vaginal dryness in women with baseline symptoms but increased breast tenderness. The likelihood of experiencing symptoms was significantly higher after stopping CEE than placebo regardless of baseline symptom status. These potential effects should be considered before initiating CEE to relieve menopausal symptoms.’

Comment
The above concluding sentences of the article by Brunner and colleagues seem to be warning symptomatic women to think again and again before making a decision on whether to use hormone therapy. If one reads the whole paper, trying to understand the above quotation, it looks as if the message may be summarized as follows: (1) yes, CEE relieves menopausal symptoms; (2) stopping CEE may lead to a recurrence of symptoms in about 30% of users, some of whom may therefore wish to continue therapy; (3) but long-term CEE may be troublesome and even risky; (4) this recurrence-of-symptom-phenomenon may make it difficult for some symptomatic women to follow the consensus recommendations to use CEE for a short period of time; (5) so, the final take-home message is perhaps: better avoid hormone therapy in the first place and suffer quietly.

Since the article comes from the ‘WHI factory’, long known for expressing negative attitudes in regard to postmenopausal hormone use, a more balanced view should be given as well. It is now widely accepted that the WHI was not designed to investigate the scenario of postmenopausal women who start hormone therapy near menopause and continue it for a long time. The whole benefit–risk calculations in such a clinical setting cannot be extrapolated from the WHI data, but rather from observational studies such as the Nurses’ Health Study. Furthermore, the tapering of estrogen dosage in long-term users and the application of hormonal protocols that are metabolically safer seem to reduce certain risks (breast cancer, thrombosis). The position of the International Menopause Society has always been that decisions on long-term hormone use should remain at the discretion of the individual, well-informed woman and her health-care provider. Certainly, quality-of-live issues in the menopause should be regarded at least as important as the prevention or treatment of diseases.

Amos Pines
Department of Medicine ‘T’, Ichilov Hospital, Tel-Aviv, Israel

References
1. Brunner RL, Aragaki A, Barnabei V, et al. Menopausal symptom experience before and after stopping estrogen therapy in the Women’s Health Initiative randomized, placebo-controlled trial. Menopause 2010 June 2. Epub ahead of print.
http://www.ncbi.nlm.nih.gov/pubmed/20505547