Sexual dysfunction is common among peri- and postmenopausal women and include a spectrum of problems, including low (or hypoactive) sexual desire, decreased satisfaction, and discomfort.   Reports indicate that the prevalence of hypoactive sexual desire ranges from 9% in naturally postmenopausal women up to 26% in younger surgically postmenopausal women.  A recent study compares the impact of transdermal and oral estradiol on sexual function.

This study was part of the Kronos Early Estrogen Prevention Study (KEEPS), a 4-year prospective, randomized, double-blinded, placebo-controlled trial of menopausal hormone therapy in healthy, recently menopausal women. Of 727 women enrolled in KEEPS, 670 agreed to participate in this ancillary study assessing sexual functioning. Women were between the age of 42 and 58 years and enrolled within 36 months of their last menstrual period.  Participants were randomized to receive either 0.45 mg/d oral conjugated equine estrogens (o-CEE), 50 µg/d transdermal 17?-estradiol (t-E2), or placebo. Participants also received 200 mg oral micronized progesterone (if randomized to CEE or E2) or placebo (if randomized to placebo estrogens) for 12 days each month.

Aspects of sexual function and experience (desire, arousal, lubrication, orgasm, satisfaction, and pain) were assessed using the Female Sexual Function Inventory (FSFI; range, 0-36 points, where higher scores indicate better sexual functioning). Low sexual function (LSF) was defined as an FSFI overall score of less than 26.55.

Treatment with transdermal estradiol was associated with a significant yet moderate improvement in the overall FSFI score across all time points compared to placebo. The domains that showed the greatest improvement were lubrication and pain.  In addition, the proportion of women identified with low sexual function was lower after treatment with transdermal estradiol as compared to placebo.  However, treatment with oral estrogen was no better than placebo with regard to sexual function.

This is an interesting study.  We typically think of oral and transdermal estradiol as being similarly effective for managing menopausal symptoms, such as hot flashes and sleep disturbance. However, this study indicates that transdermal estradiol may be superior to oral estradiol in terms of its effects on sexual function.  One explanation for this finding is that oral estradiol raises circulating sex hormone binding globulin (SHBG) and thus lowers free testosterone levels, which may adversely affect libido and other elements of sexual function. And there are other reasons that transdermal estradiol may be a better first choice than oral hormone preparation for peri- and post=menopausal women. In other studies of postmenopausal women, transdermal estradiol, as compared to oral estrogen, was associated with lower rates of venous thromboembolism, pulmonary embolism, and possibly stroke.

Ruta Nonacs, MD PhD



Taylor HS, Tal A, Pal L, Li F, et al. Effects of Oral vs Transdermal Estrogen Therapy on Sexual Function in Early Postmenopause: Ancillary Study of the Kronos Early Estrogen Prevention Study (KEEPS). JAMA Intern Med. 2017 Oct 1; 177(10):1471-1479.  Free Article

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