Effect of Testosterone Treatment on Clitoral Arteries' Hemodynamic Parameters. (TESTOFSD)

• ClinicalTrials.gov Identifier: NCT04336891
• Recruitment Status: Completed
• First Posted: April 7, 2020
• Last Update Posted: April 7, 2020
• Sponsor: University of Florence
• Information provided by (Responsible Party): Linda Vignozzi, MD, University of Florence

Study Description

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).

Condition or disease	Intervention/treatment
Hypoactive Sexual Desire Disorder; Vulvovaginal Disease; Menopause Related Conditions; Dyspareunia (Female Excluding Psychogenic); Hypoestrogenism; Arousal Disorders, Sexual	Drug: Testosterone gel; Drug: Estradiol ovules; Drug: Moisturizer; Drug: Testosterone gel + Estradiol ovules

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).

Study Design

• Study Type: Observational
• Actual Enrollment: 81 participants
• Observational Model: Cohort
• Time Perspective: Retrospective
• Official Title: Pilot Retrospective Study on the Effect of Testosterone Treatment on Clitoral Arteries' Hemodynamic Parameters.
• Actual Study Start Date: March 20, 2019
• Actual Primary Completion Date: December 31, 2019
• Actual Study Completion Date: March 31, 2020

Groups and Cohorts

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

Outcome Measures

Primary Outcome Measures :

1. Changes of clitoral artery peak systolic velocity (PSV) in women treated with testosterone gel [ Time Frame: 6 months ]
   parameter evaluated at clitoral color Doppler ultrasound
2. Changes of clitoral artery pulsatility index (PI) in women treated with testosterone gel [ Time Frame: 6 months ]
   parameter evaluated at clitoral color Doppler ultrasound
3. Changes of clitoral artery acceleration (ACC) in women treated with testosterone gel [ Time Frame: 6 months ]
   parameter evaluated at clitoral color Doppler ultrasound

Secondary Outcome Measures :

1. Difference in changes of clitoral artery PSV among the 4 intervention groups [ Time Frame: 6 months ]
2. Difference in changes of clitoral artery PI among the 4 intervention groups [ Time Frame: 6 months ]
3. Difference in changes of clitoral artery ACC among the 4 intervention groups [ Time Frame: 6 months ]

Other Outcome Measures:

1. Changes in Female Sexual Function Index (FSFI) Total, desire, arousal, lubrication, orgasm, satisfaction and pain scores, in women treated with transdermal Testosterone [ Time Frame: 6 months ]
2. Changes in serum total Testosterone levels in women treated with transdermal Testosterone [ Time Frame: 6 months ]
   Women were asked to have blood samples drawn in the morning, after an overnight fast, during the early follicular phase (if premenopausal)
3. Changes in serum total Sex Hormone Binding Globulin (SHBG) levels in women treated with transdermal Testosterone [ Time Frame: 6 months ]
   Women were asked to have blood samples drawn in the morning, after an overnight fast, during the early follicular phase (if premenopausal)
4. Difference in changes of - Total cholesterol, high-density lipoprotein cholesterol, triglycerides, glycated hemoglobin, fasting glucose and insulin levels among the 4 intervention groups [ Time Frame: 6 months ]
   Women were asked to have blood samples drawn in the morning, after an overnight fast

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Accepts Healthy Volunteers: No
• 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.

Criteria

Inclusion Criteria:

• being heterosexual.

Exclusion Criteria:

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

Contacts and Locations

Locations

Italy

Andrology, Women's Endocrinology and Gender Incongruence Unit, University of Florence, Azienda Ospedaliero-Universitaria Careggi

Florence, Italy, 50136

Sponsors and Collaborators

University of Florence

More Information

Publications:

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.

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. Review.

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Linda Vignozzi, MD, Associate Professor of Endocrinology; Chief of Andrology, Women's Endocrinology and Gender Incongruence, Careggi Hospital, University of Florence
• ClinicalTrials.gov Identifier: NCT04336891
• Other Study ID Numbers: FEMENDO1; 14457_oss ( Other Identifier: AOU Careggi Ethics Committee )
• First Posted: April 7, 2020
• Last Update Posted: April 7, 2020
• Last Verified: April 2020

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Linda Vignozzi, MD, University of Florence:

testosterone; female sexual dysfunction; genital vascularization; clitoris; dyspareunia

Additional relevant MeSH terms:

Dyspareunia; Disease; Sexual Dysfunctions, Psychological; Pathologic Processes; Sexual Dysfunction, Physiological; Mental Disorders; Methyltestosterone; Estradiol 17 beta-cypionate; Estradiol 3-benzoate; Estradiol; Polyestradiol phosphate; Testosterone; Testosterone undecanoate; Testosterone enanthate; Testosterone 17 beta-cypionate; Estrogens; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Female; Androgens; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Anabolic Agents