From the Editor
Hormone therapy for menopausal vasomotor symptoms
Given our available (better) options for treating hot flashes, can we reduce our use of medroxyprogesterone acetate?
As far as CHD is concerned, the impact of age (or time since menopause) on the vascular response to HT in women and in nonhuman models has generated support for a “critical window” or timing hypothesis, which postulates that estrogen reduces the development of early stages of atherosclerosis while causing plaque destabilization and other adverse effects when advanced atherosclerotic lesions are present. Recent studies from Scandinavia provide additional support for this hypothesis (see the sidebar below).
What this EVIDENCE means for practice
Long-term follow-up of women who participated in the WHI clarifies the benefit-risk profile of systemic HT, underscoring that the benefit-risk ratio is greatest in younger menopausal women.
Because the safety of HT is greater in women nearer the onset of menopause, as well as in those at lower baseline risk of cardiovascular disease (CVD), individualized risk assessment may improve the benefit-risk profile and safety of HT. One approach to decision-making for women with bothersome menopausal symptoms is the MenoPro app, a free mobile app from the North American Menopause Society, with modes for both clinicians and patients.
Further evidence that HT is safe when initiated soon after menopause
Tuomikoski P, Lyytinen H, Korhonen P, et al. Coronary heart disease mortality and hormone therapy before and after the Women’s Health Initiative. Obstet Gynecol. 2014;124(5):947–953.
In Finland, all deaths are recorded in a national register, in which particular attention is paid to accurately classifying those thought to result from coronary heart disease (CHD). In addition, since 1994, all HT users have been included in a national health insurance database, enabling detailed assessment of HT use and coronary artery disease. Investigators assessed CHD mortality from 1995 to 2009 in more than 290,000 HT users, comparing them with the background population matched for year and age.
Use of HT was associated with reductions in the CHD mortality rate of 18% to 29% (for ≤1 year of use) and 43% to 54% (for 1–8 years of use). Similar trends were noted for EPT and ET. The HT-associated protection against CHD mortality was more pronounced in users younger than 60.
Tuomikoski and colleagues concluded, and I concur, that the observational nature of their data does not allow us to recommend HT specifically to prevent CHD. Nonetheless, these findings, along with long-term follow-up data from the WHI, make the case that, for menopausal women who are younger than 60 or within 10 years of the onset of menopause, clinicians may consider initiating HT to treat bothersome vasomotor symptoms, a safe strategy with respect to CHD.
—Andrew M. Kaunitz, MD
In hysterectomized women, supraphysiologic doses of testosterone improve parameters of sexual function
Huang G, Basaria S, Travison TG, et al. Testosterone dose-response relationships in hysterectomized women with or without oophorectomy: effects on sexual function, body composition, muscle performance, and physical function in a randomized trial. Menopause. 2014;21(6):612–623.
No formulation of testosterone is approved by the US Food and Drug Administration (FDA) for use in women. Nonetheless, in the United States, many menopausal women hoping to boost their sexual desire are prescribed, off-label, testosterone formulations indicated for use in men, as well as compounded formulations.2
Investigators randomly allocated women who had undergone hysterectomy to 12 weeks of transdermal estradiol followed by 24 weekly intramuscular injections of placebo or testosterone enanthate at doses of 3.0 mg, 6.0 mg, 12.5 mg, or 25.0 mg while continuing estrogen. At the outset of the trial, all women had serum free testosterone levels below the range for healthy premenopausal women.
Among the 62 women who received testosterone, serum testosterone levels increased in a dose-related fashion. Among those allocated to the highest dose, serum total testosterone levels at 24 weeks were 5 to 6 times higher than values in healthy premenopausal women. Compared with women who received placebo, those who received the highest testosterone dose had better measures of sexual desire, arousal, and frequency of sexual activity. Excess hair growth was significantly more common in women who received the 2 highest doses of testosterone.
What this EVIDENCE means for practice
Although this well-executed study was small and short-term, it confirms that, in menopausal women receiving estrogen, testosterone can enhance parameters of sexuality. It is unfortunate that the dose needed to achieve this benefit results in markedly supraphysiologic serum testosterone levels.
One important caveat raised by this trial: It did not specifically recruit participants with low sexual desire. Therefore, it remains unknown whether lower doses of testosterone might provide benefits in women with low baseline libido. Regrettably, no randomized trials have addressed the long-term benefits and risks of use of testosterone among menopausal women.
