Menopausal Hormonal Therapy: More Good News for Women

For those of us who have been caring for menopausal women for many years, including during the turbulent times right after the results of the Estrogen plus Progestin arm of the Women's Health Initiative were published, as well as for those of us who are new to the practice of caring for menopausal women, the article by Sebastian et al. is yet another positive milestone in women's health. Clearly these data add to several other studies confirming that older women do not have to grin and bear it or have to increase their relative risk of osteoporotic morbidity and mortality by shunning pharmacological agents that can ameliorate or prevent many adverse outcomes. And one such novel pharmacological approach is the utilization of a tissue-selective estrogen complex (TSEC), such as conjugated estrogens plus bazedoxifene as noted in the said article presenting pooled analysis data of five phase 3 trials.

The use of a TSEC, which pairs one or more estrogens partnered with a selective estrogen receptor modulator (SERM), makes sense. With TSEC interventions, nonhysterectomized women receive all of the benefits of the estrogen without the need for a progestin. Since the estrogen is the main therapeutic intervention and the progestin is basically needed for protection of the endometrial lining, the use of an SERM component with an estrogen intervention is an effective and safe approach. And having confirmation that this particular TSEC (conjugated estrogens plus bazedoxifene) provides endometrial protection without causing other distressing side effects such as breast pain and vaginal bleeding or adverse laboratory finding such as increased breast density and ovarian cysts adds to options that clinicians can offer menopausal women who would benefit from menopausal hormonal intervention.

What is particularly encouraging with the conjugated estrogens/bazedoxifene intervention is that it is an effective intervention in not only eliminating or ameliorating vasomotor symptoms but also improving measures of vaginal atrophy and preserving bone mass. And adding to the positive effects of the TSEC, data suggest that it does not significantly increase body mass index or body weight in postmenopausal women when compared with placebo. ¹ Even though menopause is associated with changes in body weight and adipose distribution and many women shun menopausal hormonal therapy because of fear of weight gain, data do not support this adverse outcome with conjugated estrogens plus bazedoxifene.

One other point that this article highlights is the large number of subjects who participated in the study of this TSEC to fulfill the rigorous FDA requirements in establishing drug safety and efficacy. As the authors note, 4409 subjects were included in the overall pooled gynecological safety population. This is compared with non-FDA-approved compounded bioidentical hormone therapies (CBHTs) that do not go through the same rigorous testing. Without FDA approval, these CBHTs are more subject to being inconsistently compounded as well as being misbranded or adulterated. ² Other interventions also need rigorous trials with placebo arms, as noted in the recently published pilot trial done in the UK that evaluated the use of herbs and/or acupuncture in conjunction with dietary and lifestyle recommendations. ³

For all clinicians who care for menopausal women, the data continue to support safety and efficacy of pharmacological interventions for our postmenopausal women, including the TSEC-conjugated estrogens/bazedoxifene, who have undergone rigorous trials. From these placebo controlled multicenter trials, clinicians and their patients have the data that outline to them the benefits and risks of intervention.