Hormonal and Non-Hormonal Management of Vasomotor Symptoms: A Narrated Review

Background: Vasomotor symptoms (VMS; hot flashes, hot flushes) are the most common complaints of periand postmenopausal women. Therapies include various estrogens and estrogen-progestogen combinations. However, both physicians and patients became concerned about hormone-related therapies following publication of data by the Women’s Health Initiative (WHI) study and have turned to non-hormonal approaches of varying effectiveness and risks. Objective: Comparison of the efficacy of non-hormonal VMS therapies with estrogen replacement therapy (ERT) or ERT combined with progestogen (Menopausal Hormone Treatment; MHT) and the development of literature-based guidelines for the use of hormonal and non-hormonal VMS therapies. Methods: Pubmed, Cochrane Controlled Clinical Trials Register Database and Scopus were searched for relevant clinical trials that provided data on the treatment of VMS up to June 2013. Findings: Depending on the dose, ERT using any of several types of estrogen receptor (ER) ligands is unequivocally the most effective treatment for VMS. In most studies, the selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tibolone, clonidine and gabapentin are more effective than placebo. Paroxetine, which is an SSRI, is the only FDA-approved non-hormonal agent for the treatment of VMS. SSRIs must be used with caution in women with breast cancer receiving adjuvant tamoxifen therapy since SSRIs reduce the metabolism of tamoxifen to its most active metabolite, endoxifen. Although gabapentin and some of the SNRIs may be effective in relieving VMS, there are safety concerns with their use such as increased risk of suicidal thoughts with gabapentin and hepatotoxicity and increased rate of cardiovascular events with desvenlafaxine. Oral micronized progesterone is effective for treatment of VMS in early postmenopausal women. Bazedoxifene/conjugated estrogen may be a promising alternative to hormone therapy for the treatment of VMS. The effects of phytoestrogens on VMS are similar to placebo. Black cohoshes, dong quai, evening primrose oil, ginseng extract, kava kava, vitamin E, red clover leaf, hypnosis, acupuncture are either ineffective or not clinically significantly efficacious in the treatment of VMS. Conclusions: VMS vary greatly in severity, and women with mild to moderate symptoms may not need to use ERT/MHT, or any treatment at all. However if used, ERT or MHT is effective for the treatment of VMS. Initial one to three month trials for efficacy and tolerance are recommended since relief from VMS is usually substantial within 4 weeks of starting ERT/MHT. As with all treatments, the risks and benefits of estrogen treatments and neurotransmitteractive treatments must be reviewed before they are administered. Randomized double blind controlled trials comparing paroxetine, SNRIs, clonidine, dehydroepiandrostenedione or stellate ganglion block with ERT/MHT are needed to confirm their efficacy and side effect profiles. So-called “bioidenticals” have no advantage over conventional preparations and are not subject to FDA standards.