Clinical trial NCT04336891: Effect of Testosterone Treatment on Clitoral Arteries' Hemodynamic Parameters.
Official title: Pilot Retrospective Study on the Effect of Testosterone Treatment on Clitoral Arteries' Hemodynamic Parameters.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hypoactive Sexual Desire Disorder
Vulvovaginal Disease
Menopause Related Conditions
Dyspareunia (Female Excluding Psychogenic)
Hypoestrogenism
Arousal Disorders, Sexual
Keywords: testosterone
female sexual dysfunction
genital vascularization
clitoris
dyspareunia
Lead sponsor: University of Florence
Sponsor class: OTHER
First posted: 2020-04-07
Enrollment: 81
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Pre- and postmenopausal women who attended our outpatient clinic at Andrology, Women's Endocrinology and Gender Incongruence Unit, University of Florence (Florence, Italy) for sexual concerns.

Brief summary: 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: 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).

Eligibility criteria: Inclusion Criteria:

* being heterosexual.

Exclusion Criteria:

* history of drug or alcohol abuse
* a diagnosis of uncontrolled or unstable mental or organic disease.

Primary outcomes:
measure: Changes of clitoral artery peak systolic velocity (PSV) in women treated with testosterone gel
timeFrame: 6 months
measure: Changes of clitoral artery pulsatility index (PI) in women treated with testosterone gel
timeFrame: 6 months
measure: Changes of clitoral artery acceleration (ACC) in women treated with testosterone gel
timeFrame: 6 months
Secondary outcomes:
measure: Difference in changes of clitoral artery PSV among the 4 intervention groups
timeFrame: 6 months
measure: Difference in changes of clitoral artery PI among the 4 intervention groups
timeFrame: 6 months
measure: Difference in changes of clitoral artery ACC among the 4 intervention groups
timeFrame: 6 months
Other outcomes:
measure: Changes in Female Sexual Function Index (FSFI) Total, desire, arousal, lubrication, orgasm, satisfaction and pain scores, in women treated with transdermal Testosterone
timeFrame: 6 months
measure: Changes in serum total Testosterone levels in women treated with transdermal Testosterone
timeFrame: 6 months
measure: Changes in serum total Sex Hormone Binding Globulin (SHBG) levels in women treated with transdermal Testosterone
timeFrame: 6 months
measure: Difference in changes of - Total cholesterol, high-density lipoprotein cholesterol, triglycerides, glycated hemoglobin, fasting glucose and insulin levels among the 4 intervention groups
timeFrame: 6 months
Locations:
city: Florence
country: Italy
facility: Andrology, Women's Endocrinology and Gender Incongruence Unit, University of Florence, Azienda Ospedaliero-Universitaria Careggi
Study officials:
References:
citation: Scavello I, Maseroli E, Di Stasi V, Cipriani S, Verde N, Magini A, Maggi M, Vignozzi L. Nomegestrol acetate/17beta-estradiol does not negatively alter the vascular resistance of clitoral arteries: a prospective, exploratory study. Int J Impot Res. 2020 Mar;32(2):239-247. doi: 10.1038/s41443-019-0162-7. Epub 2019 Jul 1.
citation: Maseroli E, Scavello I, Vignozzi L. Cardiometabolic Risk and Female Sexuality-Part II. Understanding (and Overcoming) Gender Differences: The Key Role of an Adequate Methodological Approach. Sex Med Rev. 2018 Oct;6(4):525-534. doi: 10.1016/j.sxmr.2018.03.004. Epub 2018 Apr 13.
citation: Davis SR, Baber R, Panay N, Bitzer J, Perez SC, Islam RM, Kaunitz AM, Kingsberg SA, Lambrinoudaki I, Liu J, Parish SJ, Pinkerton J, Rymer J, Simon JA, Vignozzi L, Wierman ME. Global Consensus Position Statement on the Use of Testosterone Therapy for Women. J Clin Endocrinol Metab. 2019 Oct 1;104(10):4660-4666. doi: 10.1210/jc.2019-01603.
citation: Cipriani S, Maseroli E, Di Stasi V, Scavello I, Todisco T, Rastrelli G, Fambrini M, Sorbi F, Petraglia F, Jannini EA, Maggi M, Vignozzi L. Effects of testosterone treatment on clitoral haemodynamics in women with sexual dysfunction. J Endocrinol Invest. 2021 Dec;44(12):2765-2776. doi: 10.1007/s40618-021-01598-1. Epub 2021 Jun 12.