Effects of oral vs transdermal estrogen therapy on sexual function in early postmenopause: Ancillary study of the Kronos Early Estrogen Prevention Study (KEEPS)

Hugh S. Taylor, Aya Tal, Lubna Pal, Fangyong Li, Dennis M. Black, Eliot A. Brinton, Matthew J. Budoff, Marcelle I. Cedars, Wei Du, Howard N. Hodis, Rogerio A. Lobo, Jo Ann E. Manson, George R. Merriam, Virginia M Miller, Frederick Naftolin, Genevieve Neal-Perry, Nanette F. Santoro, Sherman M. Harman

Research output: Contribution to journalArticle

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Abstract

IMPORTANCE: Sexual dysfunction, an important determinant of women’s health and quality of life, is commonly associated with declining estrogen levels around the menopausal transition. OBJECTIVE: To determine the effects of oral or transdermal estrogen therapy vs placebo on sexual function in postmenopausal women. DESIGN, SETTING, AND PARTICIPANTS: Ancillary study 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 KEEPS enrollees, 670 agreed to participate in this multicenter ancillary study. Women were 42 to 58 years old, within 36 months from last menstrual period. Data were collected from July 2005 through June 2008 and analyzed from July 2010 through June 2017. INTERVENTIONS: Women were randomized to either 0.45 mg/d oral conjugated equine estrogens (o-CEE), 50 μg/d transdermal 17β-estradiol (t-E2), or placebo. Participants also received 200 mg oral micronized progesterone (if randomized to o-CEE or t-E2) or placebo (if randomized to placebo estrogens) for 12 days each month. MAIN OUTCOMES AND MEASURES: 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; higher scores indicate better sexual function). Low sexual function (LSF) was defined as an FSFI overall score of less than 26.55. Distress related to low FSFI score (required for the diagnosis of sexual dysfunction) was not evaluated. RESULTS: The 670 participants had a mean (SD) age of 52.7 (2.6) years. The t-E2 treatment was associated with a significant yet moderate improvement in the FSFI overall score across all time points compared with placebo (average efficacy, 2.6; 95% CI, 1.11-4.10; adjusted P = .002). With o-CEE treatment, there was no significant difference in FSFI overall score compared with placebo (mean efficacy, 1.4; 95% CI, −0.1 to 2.8; adjusted P = .13). There was no difference in FSFI overall score between the t-E2 and o-CEE groups on average across 48 months (adjusted P = .22). In the individual domains of sexual function, t-E2 treatment was associated with a significant increase in mean lubrication (0.61; 95% CI, 0.25-0.97; P = .001) and decreased pain (0.67; 95% CI, 0.25-1.09; P = .002) compared with placebo. Overall, the proportion of women with LSF was significantly lower after t-E2 treatment compared with placebo (67%; 95% CI, 55%-77% vs 76%; 95% CI, 67%-83%; P = .04). For o-CEE there was no significant reduction in the odds of LSF. CONCLUSIONS AND RELEVANCE: Treatment with t-E2 modestly improved sexual function in early postmenopausal women, but whether it relieved symptoms of distress is not known. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00154180.

Original languageEnglish (US)
Pages (from-to)1471-1479
Number of pages9
JournalJAMA Internal Medicine
Volume177
Issue number10
DOIs
StatePublished - Oct 1 2017

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Postmenopause
Estrogens
Placebos
Conjugated (USP) Estrogens
Lubrication
Therapeutics
Orgasm
Pain
Women's Health
Arousal
Multicenter Studies
Progesterone
Estradiol
Quality of Life
Hormones
Equipment and Supplies

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Effects of oral vs transdermal estrogen therapy on sexual function in early postmenopause : Ancillary study of the Kronos Early Estrogen Prevention Study (KEEPS). / Taylor, Hugh S.; Tal, Aya; Pal, Lubna; Li, Fangyong; Black, Dennis M.; Brinton, Eliot A.; Budoff, Matthew J.; Cedars, Marcelle I.; Du, Wei; Hodis, Howard N.; Lobo, Rogerio A.; Manson, Jo Ann E.; Merriam, George R.; Miller, Virginia M; Naftolin, Frederick; Neal-Perry, Genevieve; Santoro, Nanette F.; Harman, Sherman M.

In: JAMA Internal Medicine, Vol. 177, No. 10, 01.10.2017, p. 1471-1479.

Research output: Contribution to journalArticle

Taylor, HS, Tal, A, Pal, L, Li, F, Black, DM, Brinton, EA, Budoff, MJ, Cedars, MI, Du, W, Hodis, HN, Lobo, RA, Manson, JAE, Merriam, GR, Miller, VM, Naftolin, F, Neal-Perry, G, Santoro, NF & Harman, SM 2017, 'Effects of oral vs transdermal estrogen therapy on sexual function in early postmenopause: Ancillary study of the Kronos Early Estrogen Prevention Study (KEEPS)', JAMA Internal Medicine, vol. 177, no. 10, pp. 1471-1479. https://doi.org/10.1001/jamainternmed.2017.3877
Taylor, Hugh S. ; Tal, Aya ; Pal, Lubna ; Li, Fangyong ; Black, Dennis M. ; Brinton, Eliot A. ; Budoff, Matthew J. ; Cedars, Marcelle I. ; Du, Wei ; Hodis, Howard N. ; Lobo, Rogerio A. ; Manson, Jo Ann E. ; Merriam, George R. ; Miller, Virginia M ; Naftolin, Frederick ; Neal-Perry, Genevieve ; Santoro, Nanette F. ; Harman, Sherman M. / Effects of oral vs transdermal estrogen therapy on sexual function in early postmenopause : Ancillary study of the Kronos Early Estrogen Prevention Study (KEEPS). In: JAMA Internal Medicine. 2017 ; Vol. 177, No. 10. pp. 1471-1479.
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abstract = "IMPORTANCE: Sexual dysfunction, an important determinant of women’s health and quality of life, is commonly associated with declining estrogen levels around the menopausal transition. OBJECTIVE: To determine the effects of oral or transdermal estrogen therapy vs placebo on sexual function in postmenopausal women. DESIGN, SETTING, AND PARTICIPANTS: Ancillary study 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 KEEPS enrollees, 670 agreed to participate in this multicenter ancillary study. Women were 42 to 58 years old, within 36 months from last menstrual period. Data were collected from July 2005 through June 2008 and analyzed from July 2010 through June 2017. INTERVENTIONS: Women were randomized to either 0.45 mg/d oral conjugated equine estrogens (o-CEE), 50 μg/d transdermal 17β-estradiol (t-E2), or placebo. Participants also received 200 mg oral micronized progesterone (if randomized to o-CEE or t-E2) or placebo (if randomized to placebo estrogens) for 12 days each month. MAIN OUTCOMES AND MEASURES: 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; higher scores indicate better sexual function). Low sexual function (LSF) was defined as an FSFI overall score of less than 26.55. Distress related to low FSFI score (required for the diagnosis of sexual dysfunction) was not evaluated. RESULTS: The 670 participants had a mean (SD) age of 52.7 (2.6) years. The t-E2 treatment was associated with a significant yet moderate improvement in the FSFI overall score across all time points compared with placebo (average efficacy, 2.6; 95{\%} CI, 1.11-4.10; adjusted P = .002). With o-CEE treatment, there was no significant difference in FSFI overall score compared with placebo (mean efficacy, 1.4; 95{\%} CI, −0.1 to 2.8; adjusted P = .13). There was no difference in FSFI overall score between the t-E2 and o-CEE groups on average across 48 months (adjusted P = .22). In the individual domains of sexual function, t-E2 treatment was associated with a significant increase in mean lubrication (0.61; 95{\%} CI, 0.25-0.97; P = .001) and decreased pain (0.67; 95{\%} CI, 0.25-1.09; P = .002) compared with placebo. Overall, the proportion of women with LSF was significantly lower after t-E2 treatment compared with placebo (67{\%}; 95{\%} CI, 55{\%}-77{\%} vs 76{\%}; 95{\%} CI, 67{\%}-83{\%}; P = .04). For o-CEE there was no significant reduction in the odds of LSF. CONCLUSIONS AND RELEVANCE: Treatment with t-E2 modestly improved sexual function in early postmenopausal women, but whether it relieved symptoms of distress is not known. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00154180.",
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T1 - Effects of oral vs transdermal estrogen therapy on sexual function in early postmenopause

T2 - Ancillary study of the Kronos Early Estrogen Prevention Study (KEEPS)

AU - Taylor, Hugh S.

AU - Tal, Aya

AU - Pal, Lubna

AU - Li, Fangyong

AU - Black, Dennis M.

AU - Brinton, Eliot A.

AU - Budoff, Matthew J.

AU - Cedars, Marcelle I.

AU - Du, Wei

AU - Hodis, Howard N.

AU - Lobo, Rogerio A.

AU - Manson, Jo Ann E.

AU - Merriam, George R.

AU - Miller, Virginia M

AU - Naftolin, Frederick

AU - Neal-Perry, Genevieve

AU - Santoro, Nanette F.

AU - Harman, Sherman M.

PY - 2017/10/1

Y1 - 2017/10/1

N2 - IMPORTANCE: Sexual dysfunction, an important determinant of women’s health and quality of life, is commonly associated with declining estrogen levels around the menopausal transition. OBJECTIVE: To determine the effects of oral or transdermal estrogen therapy vs placebo on sexual function in postmenopausal women. DESIGN, SETTING, AND PARTICIPANTS: Ancillary study 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 KEEPS enrollees, 670 agreed to participate in this multicenter ancillary study. Women were 42 to 58 years old, within 36 months from last menstrual period. Data were collected from July 2005 through June 2008 and analyzed from July 2010 through June 2017. INTERVENTIONS: Women were randomized to either 0.45 mg/d oral conjugated equine estrogens (o-CEE), 50 μg/d transdermal 17β-estradiol (t-E2), or placebo. Participants also received 200 mg oral micronized progesterone (if randomized to o-CEE or t-E2) or placebo (if randomized to placebo estrogens) for 12 days each month. MAIN OUTCOMES AND MEASURES: 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; higher scores indicate better sexual function). Low sexual function (LSF) was defined as an FSFI overall score of less than 26.55. Distress related to low FSFI score (required for the diagnosis of sexual dysfunction) was not evaluated. RESULTS: The 670 participants had a mean (SD) age of 52.7 (2.6) years. The t-E2 treatment was associated with a significant yet moderate improvement in the FSFI overall score across all time points compared with placebo (average efficacy, 2.6; 95% CI, 1.11-4.10; adjusted P = .002). With o-CEE treatment, there was no significant difference in FSFI overall score compared with placebo (mean efficacy, 1.4; 95% CI, −0.1 to 2.8; adjusted P = .13). There was no difference in FSFI overall score between the t-E2 and o-CEE groups on average across 48 months (adjusted P = .22). In the individual domains of sexual function, t-E2 treatment was associated with a significant increase in mean lubrication (0.61; 95% CI, 0.25-0.97; P = .001) and decreased pain (0.67; 95% CI, 0.25-1.09; P = .002) compared with placebo. Overall, the proportion of women with LSF was significantly lower after t-E2 treatment compared with placebo (67%; 95% CI, 55%-77% vs 76%; 95% CI, 67%-83%; P = .04). For o-CEE there was no significant reduction in the odds of LSF. CONCLUSIONS AND RELEVANCE: Treatment with t-E2 modestly improved sexual function in early postmenopausal women, but whether it relieved symptoms of distress is not known. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00154180.

AB - IMPORTANCE: Sexual dysfunction, an important determinant of women’s health and quality of life, is commonly associated with declining estrogen levels around the menopausal transition. OBJECTIVE: To determine the effects of oral or transdermal estrogen therapy vs placebo on sexual function in postmenopausal women. DESIGN, SETTING, AND PARTICIPANTS: Ancillary study 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 KEEPS enrollees, 670 agreed to participate in this multicenter ancillary study. Women were 42 to 58 years old, within 36 months from last menstrual period. Data were collected from July 2005 through June 2008 and analyzed from July 2010 through June 2017. INTERVENTIONS: Women were randomized to either 0.45 mg/d oral conjugated equine estrogens (o-CEE), 50 μg/d transdermal 17β-estradiol (t-E2), or placebo. Participants also received 200 mg oral micronized progesterone (if randomized to o-CEE or t-E2) or placebo (if randomized to placebo estrogens) for 12 days each month. MAIN OUTCOMES AND MEASURES: 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; higher scores indicate better sexual function). Low sexual function (LSF) was defined as an FSFI overall score of less than 26.55. Distress related to low FSFI score (required for the diagnosis of sexual dysfunction) was not evaluated. RESULTS: The 670 participants had a mean (SD) age of 52.7 (2.6) years. The t-E2 treatment was associated with a significant yet moderate improvement in the FSFI overall score across all time points compared with placebo (average efficacy, 2.6; 95% CI, 1.11-4.10; adjusted P = .002). With o-CEE treatment, there was no significant difference in FSFI overall score compared with placebo (mean efficacy, 1.4; 95% CI, −0.1 to 2.8; adjusted P = .13). There was no difference in FSFI overall score between the t-E2 and o-CEE groups on average across 48 months (adjusted P = .22). In the individual domains of sexual function, t-E2 treatment was associated with a significant increase in mean lubrication (0.61; 95% CI, 0.25-0.97; P = .001) and decreased pain (0.67; 95% CI, 0.25-1.09; P = .002) compared with placebo. Overall, the proportion of women with LSF was significantly lower after t-E2 treatment compared with placebo (67%; 95% CI, 55%-77% vs 76%; 95% CI, 67%-83%; P = .04). For o-CEE there was no significant reduction in the odds of LSF. CONCLUSIONS AND RELEVANCE: Treatment with t-E2 modestly improved sexual function in early postmenopausal women, but whether it relieved symptoms of distress is not known. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00154180.

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