Genetic Polymorphism of the Androgen Receptor-Gene and Sexual Function in Middle Aged Women (CAG-Libido)

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.

Study Overview

• Status: Completed
• Conditions: Polymorphism, Genetic; Libido; Receptors, Androgen; Androgen Effect

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.

• Study Type: Observational
• Enrollment (Actual): 45

Contacts and Locations

Study Locations

• Switzerland
  • Bern, Switzerland, 3010 Bern
    • Dep. of gynaecological Endocrinology and reproduction medicine, Clinic for Gynaecology and Obstetrics, Bern University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

A community sample of 45 healthy heterosexual women, aged 45-65.

Description

Inclusion Criteria:

• Female
• Healthy
• Heterosexual
• Aged 45-65
• Written Informed Consent
• Living since at least 1 year in a relationship
• Ready to answer questionnaires about their sexual function
• Ready to give a blood sample
• German speaking

Exclusion Criteria

• Serious diseases such as Cancer, Parkinsons Disease, Multiple Sclerosis, Diabetes mellitus
• Sexual Abuse in personal history
• Thyroid dysfunction
• Substance abuse (>1pack/cigarettes per day, alcohol, drugs)
• Psychiatric diseases in personal history
• Acute stressful life event
• Libido affecting diseases such as dyspareunia, vaginism, orgasm disorders, urine incontinence
• Medication with the following substances in the past 8 weeks before day of visit:
• Systemic corticoids
• Blood pressure medication with beta-blockers, spironolactone, thiazide diuretics
• Psychotropic medication such as antidepressants, benzodiazepins, antiepileptics, antipsychotics (1st generation)
• Opioid analgetics
• Hormonal contraceptives
• Libido stimulating medication such as androgens (Testosterone, Dehydroepiandrostendionsulfate, Dihydrotestosterone and PDE5-Inhibitants
• Antiandrogens

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
All study participants

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
2 Subscores of the Female Sexual Function Index (FSFI): Satisfaction and Desire	1 Day of visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Other 4 Subscores of the FSFI: Arousal, Lubrication, Orgasm and Pain		1 Day of visit
CAG-repeats of the androgen receptor gene		1 Day of visit
Testosterone serum levels		1 Day of visit
Androgenity score	Calculated from Gender-specific Index of Testosterone serum levels, CAG repeats and libido scores	1 Day of visit
Other influences on libido in middle aged women		1 Day of visit

Collaborators and Investigators

• Sponsor: University Hospital Inselspital, Berne
• Collaborators: University of Zurich; University Hospital Muenster
• Investigators: Principal Investigator: Petra Stute, PD Dr. med., Clinic for Gynaecology and Obstetrics, Insel University Hospital Bern, Switzerland

Study record dates

Study Major Dates

• Study Start: September 1, 2013
• Primary Completion (ACTUAL): July 1, 2015
• Study Completion (ACTUAL): July 1, 2015

Study Registration Dates

• First Submitted: October 30, 2013
• First Submitted That Met QC Criteria: November 5, 2013
• First Posted (ESTIMATE): November 6, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): September 25, 2015
• Last Update Submitted That Met QC Criteria: September 24, 2015
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Other Study ID Numbers: 087/13