Hormone Therapy Improves Quality of Life in Older Women

Abstract & Commentary

By Leon Speroff, MD, Editor, Professor of Obstetrics and Gynecology, Oregon Health and Science University, Portland, is Editor for OB/GYN Clinical Alert.

Synopsis: A randomized trial similar to the WHI reported improvements in quality-of-life measurements after 1 year of hormone therapy.

Source: Welton AJ, et al. Health related quality of life after combined hormone replacement therapy: Randomised controlled trial. BMJ 2008;337:a1190; doi:10.1136/bmj.a1190.

The Women's Iinternational Study of Long Duration Oestrogen after the Menopause (WISDOM) trial was a randomized, controlled trial in the United Kingdom, Australia, and New Zealand, of 3721 women aged 50-69 treated with either combined 0.625 mg conjugated estrogens and 2.5/5.0 mg medroxyprogesterone, or placebo. The original plan was to randomize 22,300 women to the study that would last 10 years. The study was canceled in October 2002, in reaction to the initial reports from the WHI. Unfortunately, the premature cancellation precludes the possibility of any long-term data from WISDOM. This report summarizes the effect on 2130 women who completed 1 year on a collection of symptoms that relate to quality of life. There were statistically significant improvements among the treated women in the categories of vasomotor, sexual, and sleep symptoms. Treated women reported a reduction in aching joints and muscles, night sweats, insomnia, and vaginal dryness. The treated group reported more breast tenderness, but the percentages were notably low (16% in the treated group and 7% in the placebo group). There was no difference in scores related to depression.


The WISDOM trial claims that small effects on quality of life reported by the WHI and HERS can be attributed to the insensitive measurement tools used in those clinical trials. The WISDOM trial used a survey tool specifically designed to assess postmenopausal physical and emotional well-being, plus a validated, generic questionnaire, the European quality of life instrument (EuroQol). Only the specific questionnaire detected significant changes; the European generic tool did not. This emphasizes the importance of using the appropriate study tool to investigate this area of postmenopausal health. Similar results with vasomotor symptoms, sleep, and joint complaints were actually reported by the WHI, but with a smaller difference between treated and placebo groups. The WHI survey had only one question devoted to sexuality.

Both WISDOM and WHI reported no effects on the reporting of depression. This is consistent with the studies in perimenopausal women documenting a significant increase in risk of new depressive symptoms only in women with a history of adverse life events (the events are not defined or specified in the reports).1,2 The results of these two cohort studies support the argument that there is a vulnerable group of perimenopausal women who are responsible for the increase of new depression observed during the perimenopausal transition. In randomized trials of older postmenopausal women, these women should be present in equal numbers in the treated and placebo groups, and, therefore, the trials cannot assess the impact of hormone therapy on depression.

The results of the WISDOM trial are not surprising; they reflect what all clinicians have observed in their own practices. But it is good to add the statistical significance of a clinical trial to clinical experience. The most important point to be made is this: The WISDOM, WHI, and HERS trials were all similar in that they enrolled postmenopausal women heavily tilted towards the oldest age group without symptoms. It is a simple and logical conclusion that hormone therapy in a younger, symptomatic group of postmenopausal women would produce greater quality-of-life benefits than that quantified in the clinical trials. The backlash of the WHI negatively influenced clinicians and patients to hesitate in promoting hormone therapy for symptomatic postmenopausal women. Thankfully, we are now seeing a swing back to hormone therapy for symptomatic women. The WISDOM trial supports this position, but all 3 clinical trials underestimated the beneficial impact because of the age and symptom status of their participants.

There is another important lesson in the WISDOM trial. Even older postmenopausal women who are symptomatic benefit from hormone therapy. Age should not be the sole guiding factor in decision making.


  1. Freeman EW, et al. Associations of hormones and menopausal status with depressed mood in women with no history of depression. Arch Gen Psychiatry 2006;63:375-382.
  2. Cohen LS, et al. Risk for new onset of depression during the menopausal transition: The Harvard Study of Moods and Cycles. Arch Gen Psychiatry 2006;63:385-390.