Effects of Oral vs Transdermal Estrogen Therapy on Sexual Function in Early Postmenopause

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.; Løbo, Rogerio A.; Manson, Jo Ann E.; Merriam, George R.; Miller, Virginia M.; Naftolin, Frederick; Neal‐Perry, Genevieve; Santoro, Nanette; Harman, S. Mitchell

doi:10.1001/jamainternmed.2017.3877

Cited by 66 publications

(52 citation statements)

References 46 publications

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“…However current updated guidelines from the International Society for Sexual Medicine state that data do not support the use of systemic estrogen for any postmenopausal sexual dysfunction adding that vaginal estrogen's benefit to dryness and dyspareunia may increase sexual motivation (Santoro et al, 2016). A later study suggests that transdermal rather than oral route may benefit low sexual desire (Taylor et al, 2017) but only on a temporary basis.…”

Section: Clinical Implications Of Findingsmentioning

confidence: 99%

Dehydroepiandrosterone and cortisol as markers of HPA axis dysregulation in women with low sexual desire

Basson

O’Loughlin

Weinberg

et al. 2019

Psychoneuroendocrinology

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Previous research has found lower serum levels of dehydroepiandrosterone (DHEA) or its sulfated form, DHEA-S, in women diagnosed with Hypoactive Sexual Desire Disorder (HSDD). Given that DHEA and DHEA-S have multiple direct actions on the brain as well as anti-glucocorticoid properties, it is possible that lower levels of DHEA directly impact women's sexual functioning. To date, the significance of the lower DHEA levels remains unclear. To our knowledge, there has been no empirical study of stress hormones as markers of HPA dysregulation in women with HSDD. To attend to this gap, the present study utilized several measures of HPA axis functionmorning and evening cortisol and DHEA, the cortisol awakening response (CAR), diurnal cortisol slope, and cortisol:DHEA ratioand examined their relationship with sexual functioning in N = 275 women with (n = 137) and without (n = 138) HSDD. Results demonstrated multiple hormonal markers of HPA dysregulation in women diagnosed with HSDD compared to control participants, specifically, lower AM cortisol and DHEA levels, a flatter diurnal cortisol slope, and a lower CAR. Overall, results of the present study indicate that persistently low sexual desire in women is associated with HPA axis dysregulation, with both cortisol and DHEA alterations potentially detrimental to sexual desire.

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Section: Clinical Implications Of Findingsmentioning

confidence: 99%

Dehydroepiandrosterone and cortisol as markers of HPA axis dysregulation in women with low sexual desire

Basson

O’Loughlin

Weinberg

et al. 2019

Psychoneuroendocrinology

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“…[ 24 ] In a randomized clinical trial of 670 women with reduced sexual function, sexual function was improved by transdermal E2 (t‐E2) therapy compared with a placebo, with the t‐E2 treatment associated with a significant increase in average vaginal lubrication and decreased pain. [ 25 ] In men, endocrine erectile dysfunction can be common, and T plays a crucial role in regulating the expression of NO synthase and phosphodiesterase type‐5 inhibitor in the penis. [ 26 ] T replacement therapy is therefore often used, and one investigation showed that improvements in erectile dysfunction were significantly enhanced in male patients with hypogonadism who received T therapy, compared to a placebo (57% versus 16.7%).…”

Section: Discussionmentioning

confidence: 99%

Lepidiline A Improves the Balance of Endogenous Sex Hormones and Increases Fecundity by Targeting HSD17B1

Cheng

Shen

Ding

et al. 2020

Molecular Nutrition Food Res

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Scope: Maca (Lepidium meyenii), a well-known plant from the Andean highlands of Peru, has been used widely as a nutritional supplement to increase sexual function and fecundity. However, the identity of its active ingredients and how they function remain unknown. Methods and results: Chemical substances in maca are identified by UPLC-Q-TOF, and the active ingredients are screened through HotMap coupled with an artificial neural network. Lepidiline A (LA), an imidazole alkaloid, is identified as the key active compound. LA affects the balance of endogenous sex hormones in mice and improves fecundity in Drosophila. Using a molecular LA probe, 17ß-hydroxysteroid dehydrogenase type 1 (HSD17B1) is revealed to be the potential target of LA using a fishing-rod strategy. It is demonstrated with experimental data that LA targets HSD17B1 to enhance the enzyme's activity and increases its bioconversion efficiency of actively formed sex hormones including estrogen to 17 -estradiol and 4-androsten-3,7-dione to testosterone, which ultimately improves reproductive activity. Conclusion: LA improves the balance of endogenous sex hormones and increases fecundity by targeting HSD17B1. This underlying mechanism of action provides a useful insight into the application of maca in the regulation of dietary nutrition and healthy fertility.

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“…The results of this study suggest that HT in menopausal women may reduce frailty. Although specific measures of frailty were not measured in KEEPS and the women were relatively young (mean age 55 years), some chronic conditions of aging, [decreases in bone mineral density, sleep disturbances, depression, vaginal atrophy, and deposition of β amyloid in the brain], were alleviated by the HT treatments (Cintron et al, 2017;Farr, Khosla, Miyabara, Miller, & Kearns, 2013;Gleason et al, 2015;Kantarci et al, 2016;Taylor et al, 2017). In older women of Estrogen Early versus Late Intervention with Estadiol (ELITE), estrogen treatments reduced the rate of increase of carotid intima-medial thickness (Hodis et al, 2016), a result consistent with the finding of this study that estrogen lowered the endothelial-prominent GDF15 SASP.…”

Section: Discussionmentioning

confidence: 99%

Effect of menopausal hormone therapy on proteins associated with senescence and inflammation

et al. 2020

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Background Estrogen may inhibit cell senescence that contributes to age‐related disorders. This study determined the effects of menopausal hormone treatments on circulating levels of markers of cell senescence. Methods Growth differentiation factor 15 (GDF15), tumor necrosis factor receptor 1 (TNFR1), FAS, and macrophage inflammatory protein 1α (MIP1α) were measured in serum using multiplexed bead‐based assays and compared among menopausal women participating in the Kronos Early Estrogen Prevention Study randomized to either placebo (n = 38), oral conjugated equine estrogen (oCEE, n = 37), or transdermal 17β‐estradiol (tE2, n = 34). Serum levels of the senescent markers for each treatment were compared to placebo 36 months after randomization using the Wilcoxon rank sum test. Results Serum levels of GDF15, TNFR1, and FAS, but not MIP1α, were lower in both the oCEE and tE2 groups compared to placebo. The difference in levels between treatment and placebo for GDF15, TNFR1, and FAS were greater for oCEE [−108 pg/mL (p = .008), −234 pg/mL (p = .0006), and −1374 pg/mL (p < .0001), respectively] than for tE2 [−76 pg/mL (p = .072), −105 pg/mL (p = .076), and −695 pg/mL (p = .036), respectively]. Additionally, TNFR1 showed a positive association with time past menopause (correlation = 0.255, p = .019). Conclusions Circulating levels of some markers of cell senescence were lower in menopausal women treated with oCEE and tE2 compared to placebo. Differences in the magnitude of effect of the two active treatments may reflect the differences in circulating levels of estrogen metabolites due to formulation and mode of delivery. These data generate new hypotheses with regard to the effects of menopause on the biology of aging.

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Effects of Oral vs Transdermal Estrogen Therapy on Sexual Function in Early Postmenopause

Cited by 66 publications

References 46 publications

Dehydroepiandrosterone and cortisol as markers of HPA axis dysregulation in women with low sexual desire

Dehydroepiandrosterone and cortisol as markers of HPA axis dysregulation in women with low sexual desire

Lepidiline A Improves the Balance of Endogenous Sex Hormones and Increases Fecundity by Targeting HSD17B1

Effect of menopausal hormone therapy on proteins associated with senescence and inflammation

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