Testosterone Patch's Effects on the Cardiovascular System and Libido

• Sponsor: Imperial College Healthcare NHS Trust (Other)
• Overall Status: Completed
• CT.gov ID: NCT01208038
• Collaborator: Royal Brompton & Harefield NHS Foundation Trust (Other), Chelsea and Westminster NHS Foundation Trust (Other)
• Enrollment: 22
• Locations: 3
• Arm: 1
• Actual Duration (Months): 11.1
• Patients Per Site: 7.3
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

The purpose of this study is to examine the effect of the testosterone patch, in addition to hormone replacement therapy (HRT), on blood vessel walls, insulin levels and sexual desire.

Condition or Disease	Intervention/Treatment	Phase
Hypoactive Sexual Desire Disorder	Drug: Intrinsa Transdermal testosterone patch	Phase 4

Detailed Description

A woman's ovaries produce the hormone testosterone during her reproductive life but testosterone levels decline with age or when the ovaries are removed. Testosterone has been associated with sexual desire in both men and women. Low testosterone is also believed to cause symptoms of low energy. Thus testosterone is increasingly used in hormone replacement regimens to restore libido and energy in postmenopausal women.

In the past testosterone has been administered orally or via subcutaneous implants. Recently testosterone patches have been licensed for treating low libido in postmenopausal women. The testosterone patches deliver a dose of testosterone equivalent to the levels produced by the ovary during a woman's early reproductive years.

Oral testosterone can lead to changes to insulin and cholesterol levels which increase the risk of heart disease. On the contrary, testosterone patches may reduce or avoid this risk. To date, trials have predominantly focused on safety data in terms of side effects and basic blood tests. Reviews of the safety of testosterone replacement have emphasised the need for improved safety data, especially in terms of cardiovascular risk.

The investigators hypothesis that transdermal testosterone, in addition to HRT, will have no adverse effects on blood vessel walls and insulin levels and that transdermal testosterone significantly improves sexuality and psychological well-being in postmenopausal women.

Trial design:

The investigators aim to recruit 20 postmenopausal women to wear the testosterone patch for 3 months in addition to their usual hormone replacement therapy.

There will be 3 study visits - a pre study visit, week 6 and week 12. At each visit the following procedures will be performed:

• Medical history and physical examination

• Blood sample - for hormone levels, lipids and insulin levels

• Blood vessel stiffness measurements This will be performed using a small ultrasound device at the wrist with blood pressure measured every 5 minutes.

• Endothelial function (function of your arterial wall) is measured using a blood pressure cuff on each arm and finger probes on one finger of each hand. The blood pressure cuff is inflated for 5 minutes and is then deflated quickly. The finger probes will record the readings throughout this study.

• Sexual satisfaction questionnaire

Study Design

• Study Type: Interventional
• Actual Enrollment: 22 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: Pilot Study: Evaluating the Effect of 300 Micrograms Testosterone Patches in Addition to Hormone Replacement Therapy on Arterial Compliance, Insulin Resistance and Sexual Desire.
• Actual Study Start Date: Mar 1, 2011
• Actual Primary Completion Date: Feb 1, 2012
• Actual Study Completion Date: Feb 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Testosterone Testosterone transdermal patch 300micrograms, twice weekly for 12 weeks	Drug: Intrinsa Transdermal testosterone patch; 300 microgram transdermal testosterone patch, applied twice weekly for 12 weeks; Other Names: Intrinsa

Outcome Measures

Primary Outcome Measures

1. Arterial Compliance - Augmentation Index [12 weeks from baseline]

   Peripheral pressure waveforms were captured using radial artery application tonometry via the SphygmoCor apparatus (AtCor Medical Ltd., Sydney, Australia; software version 8.0). The central (ascending aortic) pressure waveform was then derived from an averaged peripheral waveform using a validated, transfer function. The augmentation index (AIx), which gives a composite measure of wave reflection and systemic arterial stiffness can then be calculated by analysis of the central waveform. Aix was defined as the difference between the first and second systolic peaks of the central pressure waveform, expressed as a percentage of the central pulse pressure.

2. Endothelial Function [12 weeks from baseline]

   Reactive Hyperaemia Index (RHI) was calculated automatically by the EndoPAT 2000 computer algorithm from the ratio of pulse wave amplitude before and after ischemia, compared to the control arm. Official reference values do not exist however a lower RHI (<2.0) is usually considered indicative of endothelial dysfunction.

Secondary Outcome Measures

1. Insulin Resistance - HOMA-IR [12 weeks from baseline]

   Blood samples were taken for fasting glucose and insulin levels. From these results, insulin resistance was then estimated using the updated homeostasis model assessment method for insulin resistance (HOMA-IR) computer algorithm. A higher HOMA-IR indicates a higher degree of insulin resistance. Typically a cutoff of HOMA-IR for identifying those with insulin resistance is 2.5.

2. Libido - B-PFSF Score [12 weeks from baseline]

   Libido was assessed at each visit using the Brief profile of female sexual function (BPFSF), a validated self-administered questionnaire for identifying Hypoactive Sexual Desire Disorder (HSDD). The BPFSF is based on 7 questions. Each question is scored on a 6-point scale from 'always' to 'never'. A total score is total score ranging from 0 to 35. Previous studies have identified a score of less than 20 as suggestive of HSDD.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 45 Years to 70 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• healthy postmenopausal women

• 45 to 70 years of age

• on HRT and willing to continue the same HRT regimen for the next 6 months

• are in a stable relationship which was started at least 6 months ago

• continue on any concomitant medications without any change during the study

• give informed consent.

Exclusion Criteria:

• have dyspareunia

• have received testosterone implants within the last 12 months or other androgen therapy within the last 6 months

• have received any medications which may interfere with the study (SSRI, anti-androgens, PDE5 inhibitors, DHEA, SERMS)

• have a significant psychiatric disorder

• have a history of breast cancer

• have diabetes, thromboembolic disorders, cardiovascular disease, any condition affecting carbohydrate metabolism, uncontrolled hypertension and uncontrolled hyperlipidaemia

• are on tibolone (due to its androgenic effect).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Chelsea and Westminster Hospital	London		United Kingdom	SW10 9NH
2	Queen Charlotte's and Chelsea Hospital	London		United Kingdom	W14 0HS
3	Royal Brompton Hospital	London		United Kingdom

Sponsors and Collaborators

• Imperial College Healthcare NHS Trust
• Royal Brompton & Harefield NHS Foundation Trust
• Chelsea and Westminster NHS Foundation Trust

Investigators

• Principal Investigator: Nick Panay, MBBS, Imperial College Healthcare NHS Trust
• Principal Investigator: John C Stevenson, MBBS, Royal Brompton and Harefield NHS Foundation Trust

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Imperial College Healthcare NHS Trust
• ClinicalTrials.gov Identifier: NCT01208038
• Other Study ID Numbers: CRO1646
• First Posted: Sep 23, 2010
• Last Update Posted: Jan 2, 2020
• Last Verified: Dec 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Imperial College Healthcare NHS Trust: Hypoactive sexual desire disorder
• Additional relevant MeSH terms: Hypokinesia; Sexual Dysfunctions, Psychological; Methyltestosterone; Testosterone; Testosterone undecanoate; Testosterone enanthate; Testosterone 17 beta-cypionate

Study Results

Participant Flow

Arm/Group Title	Testosterone
Arm/Group Description	Testosterone transdermal patch 300micrograms, twice weekly for 12 weeks Intrinsa Transdermal testosterone patch: 300 microgram transdermal testosterone patch, applied twice weekly for 12 weeks
Period Title: Overall Study
STARTED	22
COMPLETED	21
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Testosterone
Arm/Group Description	Testosterone transdermal patch 300micrograms, twice weekly for 12 weeks Intrinsa Transdermal testosterone patch: 300 microgram transdermal testosterone patch, applied twice weekly for 12 weeks
Overall Participants	21
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53.0 (6.7)
Sex: Female, Male (Count of Participants)
Female	21 100%
Male	0 0%
Region of Enrollment (Count of Participants)
United Kingdom	21 100%
Augmentation Index (percentage of Arterial stiffness) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage of Arterial stiffness]	24.21 (10.70)
Reactive Hyperaemia Index (Reactive hyperaemia index) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Reactive hyperaemia index]	1.79 (0.36)
Brief Profile of Female Sexual Function (B-PFSF) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	15.3 (9.1)
Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	0.78 (0.40)

Outcome Measures

1. Primary Outcome

Title	Arterial Compliance - Augmentation Index
Description	Peripheral pressure waveforms were captured using radial artery application tonometry via the SphygmoCor apparatus (AtCor Medical Ltd., Sydney, Australia; software version 8.0). The central (ascending aortic) pressure waveform was then derived from an averaged peripheral waveform using a validated, transfer function. The augmentation index (AIx), which gives a composite measure of wave reflection and systemic arterial stiffness can then be calculated by analysis of the central waveform. Aix was defined as the difference between the first and second systolic peaks of the central pressure waveform, expressed as a percentage of the central pulse pressure.
Time Frame	12 weeks from baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Testosterone
Arm/Group Description	Testosterone transdermal patch 300micrograms, twice weekly for 12 weeks Intrinsa Transdermal testosterone patch: 300 microgram transdermal testosterone patch, applied twice weekly for 12 weeks
Measure Participants	21
Mean (95% Confidence Interval) [percentage of Arterial stiffness]	1.067

2. Primary Outcome

Title	Endothelial Function
Description	Reactive Hyperaemia Index (RHI) was calculated automatically by the EndoPAT 2000 computer algorithm from the ratio of pulse wave amplitude before and after ischemia, compared to the control arm. Official reference values do not exist however a lower RHI (<2.0) is usually considered indicative of endothelial dysfunction.
Time Frame	12 weeks from baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Testosterone
Arm/Group Description	Testosterone transdermal patch 300micrograms, twice weekly for 12 weeks Intrinsa Transdermal testosterone patch: 300 microgram transdermal testosterone patch, applied twice weekly for 12 weeks
Measure Participants	17
Mean (95% Confidence Interval) [units on a scale]	0.06

3. Secondary Outcome

Title	Insulin Resistance - HOMA-IR
Description	Blood samples were taken for fasting glucose and insulin levels. From these results, insulin resistance was then estimated using the updated homeostasis model assessment method for insulin resistance (HOMA-IR) computer algorithm. A higher HOMA-IR indicates a higher degree of insulin resistance. Typically a cutoff of HOMA-IR for identifying those with insulin resistance is 2.5.
Time Frame	12 weeks from baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Testosterone
Arm/Group Description	Testosterone transdermal patch 300micrograms, twice weekly for 12 weeks Intrinsa Transdermal testosterone patch: 300 microgram transdermal testosterone patch, applied twice weekly for 12 weeks
Measure Participants	21
Mean (95% Confidence Interval) [units on a scale]	0.106

4. Secondary Outcome

Title	Libido - B-PFSF Score
Description	Libido was assessed at each visit using the Brief profile of female sexual function (BPFSF), a validated self-administered questionnaire for identifying Hypoactive Sexual Desire Disorder (HSDD). The BPFSF is based on 7 questions. Each question is scored on a 6-point scale from 'always' to 'never'. A total score is total score ranging from 0 to 35. Previous studies have identified a score of less than 20 as suggestive of HSDD.
Time Frame	12 weeks from baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Testosterone
Arm/Group Description	Testosterone transdermal patch 300micrograms, twice weekly for 12 weeks Intrinsa Transdermal testosterone patch: 300 microgram transdermal testosterone patch, applied twice weekly for 12 weeks
Measure Participants	21
Mean (95% Confidence Interval) [units on a scale]	5.05

Adverse Events

Time Frame	12 weeks
Arm/Group Title	Testosterone
Arm/Group Description	Testosterone transdermal patch 300micrograms, twice weekly for 12 weeks Intrinsa Transdermal testosterone patch: 300 microgram transdermal testosterone patch, applied twice weekly for 12 weeks
All Cause Mortality
	Testosterone
	Affected / at Risk (%)	# Events
Total	0/21 (0%)
Serious Adverse Events
	Testosterone
	Affected / at Risk (%)	# Events
Total	0/21 (0%)
Other (Not Including Serious) Adverse Events
	Testosterone
	Affected / at Risk (%)	# Events
Total	7/21 (33.3%)
Endocrine disorders
Increased facial hair	2/21 (9.5%)
Eye disorders
Blepharitis	1/21 (4.8%)
Reproductive system and breast disorders
per vagina spotting	1/21 (4.8%)
Skin and subcutaneous tissue disorders
Skin irritation	4/21 (19%)
Acne	1/21 (4.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.