Genetic Polymorphism of the Androgen Receptor-Gene and Sexual Function in Middle Aged Women
Condition: Libido; Receptors, Androgen; Polymorphism, Genetic; Androgen Effect
Study type: Observational

Summary: 
      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.
    

Detailed description: 
      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.
    

Observational model: Case-Only
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        A community sample of 45 healthy heterosexual women, aged 45-65.
      
Biospecimen description: 
      Whole blood, serum