Androgen Receptor Polymorphism and Female Sexual Function and Desire

Abstract

Introduction The effect of testosterone depends on the exposure of and the sensitivity of the androgen receptor (AR). It has been shown that a cytosine–adenine–guanine (CAG) trinucleotide repeat polymorphism in the AR gene has an impact on AR functional capacity in men. However, large studies are lacking on the impact of this polymorphism on female sexual function. Aim To determine whether the CAG repeat length was associated with different aspects of women’s sexual function and dysfunction, including desire, arousal, lubrication, orgasm, satisfaction, sexual pain, and sexually related personal distress. Methods This cross-sectional study included 529 healthy women, aged 19–65 years. Participants completed a questionnaire to provide demographic and sexual data. The CAG repeat length was analyzed in a blood sample. The correlations between CAG repeat lengths and different aspects of sexual function were calculated. Independent Student t-tests were performed to evaluate differences in the mean number of CAG repeats in the short and long allele and of the biallelic mean length determined by simple calculation and X-inactivation analysis, respectively, between women with sexual problems and women without sexual problems. P values <.05 were considered statistically significant. Main Outcome Measure We used the Female Sexual Function Index, with 6 subdomains, to distinguish between women without and women with impaired sexual function; low sexual desire; impaired arousal, lubrication, or orgasm; diminished satisfaction; or pain during sex. The Female Sexual Distress Scale was used to measure sexually related personal distress. Results Overall, we found that increasing numbers of CAG repeats were correlated to increased sexual function. We found that women with problems achieving orgasm had a significantly lower number of CAG repeats than women that reported no problems reaching orgasm. We found no associations between CAG repeat lengths and other aspects of female sexual dysfunction, including hypoactive sexual desire disorder. Clinical Implications The results could indicate an impact of the AR on women’s sexual function, including the ability to reach orgasm. Strength & Limitations This is a large study using validated sexual questionnaires. A limitation is the cross-sectional design. Owing to the study design, this study is explorative and hypothesis generating. Conclusion In this large cross-sectional study, we demonstrated that CAG repeat length is positively correlated to sexual function and that women with a reduced ability to reach orgasm had smaller numbers of CAG repeats in the AR gene than women with no orgasmic problems. These findings indicated that androgens and ARs might play a role in women’s sexual function.

International Society for the Study of Women's Sexual Health Clinical Practice Guideline for the Use of Systemic Testosterone for Hypoactive Sexual Desire Disorder in Women

“…Furthermore, androgenic effects vary according to individual variations in the amount and activity of the enzymes 5a-reductase and aromatase and individual differences in the AR response. 89,90 However, it is still not clear whether the AR activity is a modulator of the androgenic effect on sexual desire 90 or if levels of intracrine activity of androgens are better parameters for androgen effect on sexual desire. 83 What Is the Rationale for Testosterone Therapy in Women?…”

“…15 Increasing the woman's testosterone dose and total testosterone levels beyond physiologic range to "overcome" elevated SHBG is a clinical strategy that is not supported by current evidence on androgen metabolism, AR and intracrine effects, and short-and long-term safety. 83,89,90 In countries where tibolone is available, it can be used as an alternative MHT in women with high SHBG as tibolone lowers SHBG by approximately 45%.…”

International Society for the Study of Women's Sexual Health Clinical Practice Guideline for the Use of Systemic Testosterone for Hypoactive Sexual Desire Disorder in Women

“…Furthermore, androgenic effects vary according to individual variations in the amount and activity of the enzymes 5a-reductase and aromatase and individual differences in the AR response. 89,90 However, it is still not clear whether the AR activity is a modulator of the androgenic effect on sexual desire 90 or if levels of intracrine activity of androgens are better parameters for androgen effect on sexual desire. 83…”

An Analysis of the Implication of Estrogens and Steroid Receptor Coactivators in the Genetic Basis of Gender Incongruence

“…We must point out that the packaging of DNA into chromatin causes a general repression of gene activity, and transcription factors function to relieve this chromatin-mediated repression [33].Thereby, once attached to their ligands, the receptors dimerize, enter the nucleus, and interact with the promoter regions of the target genes, modulating the expression of multiple genes in collaboration with some steroid coactivators (Figure 1). In the case of the AR, its ligand is androgen [34] while for the ERs, it is estrogen, 17β-Estradiol (E2) in particular [26].…”