Genetic Polymorphism of the Androgen Receptor-Gene and Sexual Function in Middle Aged Women

Overview

It is known that with increasing age sexual desire is declining in women. Decreasing levels of androgens are believed to have an influence, but cannot explain the loss of libido completely. A possible explanation might be that the effect of the androgen is depending on the functionality of the androgen receptor. It is known that this functionality is genetically determined by the polymorphism of the androgen receptor gene. In the gene there is a varying number of CAG-repeats: the longer the CAG-Repeat, the lower the functionality of the androgen receptor, the lower the effect of the androgens. In this pilot study, the investigators would like to invite 45 healthy heterosexual middle-aged women to the University Hospital of Bern, where they answer questionnaires about their sexual function and where they give a blood sample to assess the testosterone serum levels and the genetically determined androgen receptor subtype. The investigators believe that lower androgen levels and/or longer CAG-repeats in the androgen receptor gene are related to lower libido scores in healthy middle-aged women.

Background It is known that with increasing age sexual desire is declining in women. Multiple factors are being discussed to have an influence on this topic, such as cultural, individual and biological factors. Decreasing levels of sexual hormones and specifically androgens are believed to have an influence, hence a lot of women benefit from a testosterone replacement therapy. Yet the sole decline of androgen levels with inclining age cannot explain the loss of libido completely. A possible further factor might be the androgen receptor: It is known that the effect of the androgen in its target cells is depending on the functionality of the androgen receptor. This functionality is genetically determined by the polymorphism of the androgen receptor gene: In the gene there is a sequence with a varying number of CAG-repeats. This CAG-repeat is coding for a polyglutamine stretch in the androgen receptor which is responsible for the binding of co-activator proteins. The better these co-activator proteins are bound to the androgen receptor, the better the transcriptional activity of the latter. Previous studies have shown that the longer the CAG-Repeat, the weaker the binding of co-activator proteins, the lower the functionality of the receptor and therefore the lower the effects of the androgen on the target cell. Given this circumstances the same level of androgen can have different effects in two individuals. Objective In this pilot study, the investigators would like to correlate the testosterone serum levels, the functionality of the androgen receptor and the libido in 45 healthy, heterosexual middle-aged women. Methods 45 healthy middle-aged women are being recruited and are being invited to come to the University Hospital in Berne. Here they will answer standardised questionnaires about their sexual function and libido and will give a blood sample to measure all the relevant parameters (fasting, premenopausal women: 1.-5. day of cycle): Total Testosterone, SHBG, Estrogen, DHEAS, FSH, LH, CAG repeats of the androgen receptor gene, TSH, fT3, fT4, Prolactin, Ferritin, CRP, Hemoglobin. A statistician will then assess the collected data. No interventions are planned. The following collaborators are providing support for this study: Dr. rer. nat. Ulrich Stefenelli, Würzburg, Germany, and Dr. med. Stefan Schmid, Rheinfelden, Switzerland.