Menopause Live - IMS Updates

Date of release: 12 May, 2014

Three alternative ways to treat VMS failed

A recent Menopause Live commentary addressed the use of complementary medicine by symptomatic women (see the April 21 edition). Needless to say that the ideal and safest therapy for vasomotor symptoms (VMS) would be healthy lifestyle ('eat right and be physically active'). The April issue of the journal Menopause includes three relevant randomized, controlled studies, all coming from the MsFLASH (Menopause Strategies: Finding Lasting Answers for Symptoms and Health) Research Network. The design and methodology of these studies were already reported last year [1]. Eligible women were randomized to yoga (n = 107), exercise (n = 106), or usual activity (n = 142), and were simultaneously randomized to a double-blind comparison of 1.8 g daily omega-3 fatty acid (n = 177) or placebo (n = 178) capsules [2-4]. The exercise intervention consisted of individual facility-based, moderate-intensity, aerobic exercise training three times per week for 12 weeks. Yoga intervention consisted of 12 weekly 90-min yoga classes with daily home practice. Primary outcomes were VMS frequency and bother assessed by daily diaries. There were no differences between the active arm and control arm (for exercise or yoga) and active arm versus placebo (omega-3 trial) at the end of 12 weeks of therapy. However, exercise and yoga were successful in improving sleep quality. Amazing as it sounds, the investigators, who managed to publish their study results in three separate articles [2-4], each describing one potential mode of alternative therapy for vasomotor symptoms, were allowed to publish another paper summarizing the above three failed therapeutic approaches [5].


The previously published contradictory evidence on the benefits of several non-hormonal, non-medicinal approaches to alleviate VMS suggests a clear need for carefully designed, randomized, controlled trials. This was the rationale for the MsFLASH initiative that was funded by the US National Institute on Aging, in the hope of promoting progress in identifying effective remedies for VMS in women experiencing the menopausal transition. The strengths of the MsFLASH data are in the methodology and the fact that the cohort was relatively homogeneous in several important aspects, such as age (around 80% were 50–59 years old), the number of daily hot flushes around 8 (95% CI 6.7–8.7), and body mass index less than 30 kg/m2 in 76% of participants. The main weakness lies in the self-reporting of symptoms through a diary. Also, there might have been a selection bias since out of 900,000 letters sent, less than 1% responded and only 355 were ultimately randomized. The results of each therapeutic approach were published in three separate articles, but were certainly frustrating since the study groups and the control/placebo groups achieved the same modest reduction in the number of hot flushes (around 2–3 fewer events per day). However, in regard to secondary outcomes in these studies, sleep and mood improved during yoga and exercise, as was expected from previous published data. Investigating the potential for omega-3 to have an effect on menopausal symptoms was a long shot, probably based on some evidence that its mechanism of action may include modulation of serotonergic and dopaminergic neurotransmission. But, by the end of the day, omega-3 did not have any effect on the primary and the secondary outcomes. An Editorial by Marcie Richardson [6] summarized this failed initiative by saying 'Where does this leave practitioners … as they attempt to help women navigate a sometimes difficult period? They can continue to recommend yoga and exercise because both contribute to the symptomatic midlife women's sense of well-being, but this is not so for omega-3'. In their overall summary on the three treatment strategies which did not demonstrate efficacy to VMS relief, the MsFLASH investigators concluded that 'All women become menopausal, and many of them seek medical advice on ways to improve quality of life; little evidence-based information exists' [5]. My personal reflective reaction would be, hey there guys, what about the best, well-proven, most efficacious way to treat VMS? Didn't you hear about estrogen? Could that be forgotten while you made your final remarks? Don't you accept the fact that, for the menopause transition and the early postmenopausal period, hormone therapy is safe for almost all women?

Amos Pines
Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel


  1. Sternfeld B, LaCroix A, Caan BJ, et al. Design and methods of a multi-site, multi-behavioral treatment trial for menopausal symptoms: the MsFLASH experience. Contemp Clin Trials 2013;35:25-34.

  2. Sternfeld B, Guthrie KA, Ensrud KE, et al. Efficacy of exercise for menopausal symptoms: a randomized controlled trial. Menopause 2014;21:330-8.

  3. Newton KM, Reed SD, Guthrie KA, et al. Efficacy of yoga for vasomotor symptoms: a randomized controlled trial. Menopause 2014;21:339-46.

  4. Cohen LS, Joffe H, Guthrie KA, et al. Efficacy of omega-3 for vasomotor symptoms treatment: a randomized controlled trial. Menopause 2014;21:347-54.

  5. Reed SD, Guthrie KA, Newton KM, et al. Menopausal quality of life: RCT of yoga, exercise, and omega-3 supplements. Am J Obstet Gynecol 2014;210:244.

  6. Richardson MK. Menopause strategies: finding lasting answers for symptoms and health: eliminating hot flashes still not a slam dunk! Menopause 2014;21:321-2.