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Transdermal oestradiol improves sexual function in early postmenopausal women

Jairia Dela Cruz
09 Nov 2017

Transdermal oestradiol therapy confers modest benefits for sexual function in early postmenopausal women, and such benefits are greater compared with that obtained with oral conjugated equine oestrogens particularly in women with low sexual function, according to the ancillary study of the Kronos Early Estrogen Prevention Study (KEEPS).

In the cohort of 670 healthy, recently menopausal women (mean age 52.7 years) randomized to receive 0.45 mg/d oral conjugated equine oestrogens (o-CEE; n=209), 50 µg/d transdermal 17β-oestradiol (t-E2; n=204) or placebo (n=257), t-E2 yielded a moderate but significant improvement in the Female Sexual Function Inventory (FSFI) score across the 48 months of treatment compared with placebo (average efficacy, 2.6; 95 percent CI, 1.11-4.10; p=0.002). [JAMA Intern Med 2017;177:1471-1479]

FSFI overall scores were comparable between t-E2 and o-CEE (p=0.22), and between o-CEE and placebo (p=0.13).

In the individual domains of sexual function, symptoms related directly to tissue effects of oestrogens on the reproductive tract were alleviated with t-E2. Compared with placebo, mean lubrication significantly increased (0.61; 0.25 to 0.97; p=0.001) while pain substantially decreased (0.67; 0.25 to 1.09; p=0.002).

On the other hand, “the more subjective domains of desire, arousal, orgasm and sexual satisfaction … were improved only at 18 months of treatment with t-E2. This may suggest that the effect of t-E2 on psychological aspects of the sexual response is independent from its effect on physiological aspects,” the investigators noted.

Low sexual function (LSF) was notably the only baseline characteristic that affected overall treatment efficacy of t-E2 and o-CEE. The overall mean effect of t-E2 treatment on FSFI scores compared with placebo was 3.7 points (p<0.001) for women with LSF at baseline vs −0.2 points (p=0.88) for women with relatively higher sexual function.

The overall o-CEE effect on FSFI score vs placebo was 2.1 points (p=0.01) in the LSF subgroup vs −0.3 points (p=0.81) in the subgroup of women with relatively higher sexual function.

“The efficacy of o-CEE treatment seemed to be less than that of t-E2, especially in the subgroup of women with LSF, although there was no statistically significant difference between the hormone groups on overall sexual function,” the investigators said, adding that the degree of improvement in FSFI with t-E2 use may be clinically meaningful.

“Temporally, t-E2 appears to be effective earlier than o-CEE (an 11.6-percent difference in improvement in FSFI score at 18 months) and last longer (a 10.3-percent difference at 48 months),” they continued.

Another observation worth noting was that controlling for changes in hot flashes, which had been associated with poor sexual function, did not significantly affect changes in either FSFI overall score or group comparisons.

The above suggests that symptom relief after treatment does not significantly contribute to the improvements observed in sexual function, according to the investigators.

Despite the large sample size and the placebo-controlled design of KEEPS, the study has several limitations. Among which are the restricted generalizability of the findings to other ethnic groups or to women with a lower educational level and socioeconomic status, as well as the inability to analyse the effect of change of partner status on the efficacy of hormone treatment as follow-up measures of partner status were not available.

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