Effect of Testosterone Treatment on Clitoral Arteries' Hemodynamic Parameters.

Study Overview
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Brief Summary
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The regulation of clitoral vascularization by sex steroids is still under-investigated. We aimed to explore the effects of 6 months transdermal Testosterone (T) therapy on clitoral color Doppler ultrasound (CDU) parameters in pre- and postmenopausal women with female sexual dysfunction (FSD). In order to do that, we retrospectively recruited n=81 women with FSD, divided into 4 groups according to different treatments followed as per clinical practice, for 6 months: transdermal systemic 2% T gel; local estradiol ovules; local non-hormonal moisturizers; transdermal T plus local estrogens. Our main hypothesis is that systemic T treatment is able to positively modulate clitoral blood flow in basal conditions, specifically to increase clitoral artery Peak systolic velocity (PSV).

Detailed Description
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Strong clinical evidence supports the use of transdermal systemic testosterone (T) treatment for Hypoactive Sexual Desire Disorder (HSDD) in menopausal women. According to preclinical studies, T is necessary to maintain the functional machinery underlying clitoral arousal response. In hypogonadal men with erectile dysfunction, T replacement therapy is able to improve penile vasodilation as assessed by using color Doppler ultrasound (CDU). On the other hand, the regulation of clitoral vascularization by sex steroids is still under-investigated. We aimed to explore the effects of 6 months T therapy on clitoral CDU parameters and sexual function in pre- and postmenopausal women with female sexual dysfunction (FSD). Adult heterosexual women attending our clinic for sexual concerns were retrospectively recruited. A subgroup of sexually active patients with FSD (n=81) was divided into 4 different groups according to different treatments followed as per clinical practice: women with Hypoactive Sexual Desire Disorder (HSDD) treated with off-label transdermal 2% T gel once daily (300 mcg T per day, n=23); women with dyspareunia due to moderate to severe vulvovaginal atrophy (VVA), treated with local estrogens (estradiol ovules) taken daily for 2 weeks and afterwards twice a week (n=12); women with dyspareunia due to mild to moderate VVA, treated with non-hormonal moisturizers every 2-3 days (n=37); women with HSDD reporting also significant dyspareunia due to moderate to severe VVA, treated with combined therapy (transdermal T and local estrogens) (n=9). Patients underwent physical, laboratory, uterine and genital (clitoral and uterine arteries) CDU examinations, and completed the Female Sexual Function Index (FSFI). at baseline and after 6 months. Our main hypothesis is that systemic T treatment is able to positively modulate clitoral blood flow in basal conditions, specifically to increase clitoral artery Peak systolic velocity (PSV).

Official Title
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Pilot Retrospective Study on the Effect of Testosterone Treatment on Clitoral Arteries' Hemodynamic Parameters.

Conditions
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Hypoactive Sexual Desire Disorder, Vulvovaginal Disease, Menopause Related Conditions, Dyspareunia (Female Excluding Psychogenic), Hypoestrogenism, Arousal Disorders, Sexual

Intervention / Treatment
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* Drug: Testosterone gel
* Drug: Estradiol ovules
* Drug: Moisturizer
* Drug: Testosterone gel + Estradiol ovules


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: being heterosexual. Exclusion Criteria: history of drug or alcohol abuse a diagnosis of uncontrolled or unstable mental or organic disease.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Hypoactive Sexual Desire Disorder<br>Women with Hypoactive Sexual Desire Disorder (HSDD, n=23) | Drug: Testosterone gel<br>* Transdermal 2% T gel applied once daily to the thighs or lower abdominal/pubic area (300 mcg T per day) for 6 months<br>|
| Moderate to severe VVA<br>Women with dyspareunia due to moderate to severe vulvovaginal atrophy (VVA) (n=12) | Drug: Estradiol ovules<br>* Intravaginal estradiol ovules taken daily for 2 weeks and afterwards twice a week, for 6 months<br>|
| Mild to moderate VVA<br>Women with dyspareunia due to mild to moderate VVA (n=37) | Drug: Moisturizer<br>* Local non-hormonal moisturizers applied regularly every 2-3 days and lubricants as needed<br>|
| HSDD + VVA<br>Women with HSDD reporting also significant dyspareunia due to moderate to severe VVA (n=9). | Drug: Testosterone gel + Estradiol ovules<br>* Transdermal 2% T gel applied once daily to the thighs or lower abdominal/pubic area (300 mcg T per day), plus Intravaginal estradiol ovules taken daily for 2 weeks and afterwards twice a week, for 6 months<br>* Other names: Estradiol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of clitoral artery peak systolic velocity (PSV) in women treated with testosterone gel | parameter evaluated at clitoral color Doppler ultrasound | 6 months | 
| Changes of clitoral artery pulsatility index (PI) in women treated with testosterone gel | parameter evaluated at clitoral color Doppler ultrasound | 6 months | 
| Changes of clitoral artery acceleration (ACC) in women treated with testosterone gel | parameter evaluated at clitoral color Doppler ultrasound | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in changes of clitoral artery PSV among the 4 intervention groups |  | 6 months | 
| Difference in changes of clitoral artery PI among the 4 intervention groups |  | 6 months | 
| Difference in changes of clitoral artery ACC among the 4 intervention groups |  | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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testosterone, female sexual dysfunction, genital vascularization, clitoris, dyspareunia