Testosterone in Female Hypoactive Sexual Desire Disorder
Information source: Beersheva Mental Health Center
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Hypoactive Sexual Desire Disorder
Intervention: testosterone gel (Androgel) (Drug)
Phase: Phase 3
Status: Completed
Sponsored by: Beersheva Mental Health Center Official(s) and/or principal investigator(s):
RH Belmaker, MD, Study Director, Affiliation: Beersheva Mental Health Center
Summary
The success of sildenafil in the treatment of erectile dysfunction has led to efforts to find
similar treatments for prevalent disorders of female sexual dysfunction. Daily transdermal
testosterone has been shown to improve sexual function in women after oophorectomy (Shifren
et al, Transdermal testosterone treatment in women with impaired sexual function after
oophorectomy, New England Journal of Medicine, 343; 682-8, 2000). In laboratory measures of
sexual arousal, a single application of transdermal testosterone enhanced vaginal blood and
increased erotic fantasy in normal volunteer women in the laboratory setting, four hours
after application (Tuiten et al, Can sublingual testosterone increase subjective and
physiological measures of laboratory-induced sexual arousal?, Arch Gen Psychiatry,
59;465,2002). We therefore planned a study of transdermal testosterone (25mg) marketed as
Androgel in female hypoactive sexual desire disorder. Patients are recruited from the
sexology clinics at Soroka Hospital and the Beersheva Mental Health Center. They are
randomized to Androgel or placebo and given 10 packets and instructed on application to the
abdomen and shoulders, four hours before planned intercourse. Patients unable to discuss
planned intercourse with their partner are offered psychosexual counseling and those still
unable after three sessions are excluded. After one month patients on active Androgel are
crossed over to placebo or vice versa. Patients self-rate sexual response after each
intercourse using the Brief Index of Sexual Functioning for Women, and Arizona Sexual
Experiences Scale (ASEX)-Female and are rated in interview at the end of each month of
treatment using the Sexual Function Questionnaire (SFQ-V1). Our prn technique avoids the
androgenizing side effects of continuous daily treatment.
Clinical Details
Official title: Transdermal Testosterone Gel Prn Application for Hypoactive Sexual Desire Disorder in Women: A Controlled Study
Study design: Treatment, Randomized, Double-Blind, Placebo Control, Crossover Assignment
Primary outcome: Arizona Sexual Experiences Scale (ASEX)Sexual Function Questionnaire (SFQ-V1)
Detailed description:
The role of androgens in addition to estrogens in female sexual health has been known for
several decades [Davis and Tran 2001]. Recently methods of delivering testosterone other
than by injection have made the use of androgens in treatment more available. Testosterone
gel is absorbed well [Wang, et al. 2000] and has been shown to be effective in the treatment
of hypogonadal men. Doses of 100 mg gel rubbed into skin increased testosterone levels to
30-40 nmoles/L within 8-20 hours. Levels returned to baseline in this study within 1-2 days
after cessation of chronic treatment although return to baseline after a single application
was not studied.
A recent study [Shifren, et al. 2000] has shown that transdermal continuous patch
testosterone dose 150micro g or 300micro g vs. placebo daily during the 12 week study
improved sexual health including desire, arousal, and orgasm frequency in women with
surgically induced menopause after oophorectomy. Blood levels reached 3. 0nmoles/L (5x
baseline). Shrifren et al [2000] found no significant side effects with transdermal
sustained testosterone treatment. Another study [Goldstat, et al. 2003] looked at
transdermal testosterone given in gel, 10mg a day given for 12 weeks in a double-blind design
for 31 pre-menopausal women with a mean age of 40 years. The women entered the study
presenting with low sexual desire. Testosterone treatment resulted in a significant
improvement in psychological general well being and sexual self rating scale. No adverse
effects were reported. Blood levels of testosterone increase about 2. 5 times baseline to
2. 6nmoles/L.
Despite the absence of side effects reported in the small studies for relatively short
periods of time done up till now in women with testosterone treatment, in the treatment of a
long term disorder such as diminished sexual desire it is reasonable to be concerned with
androgenizing side effects. Therefore, it would be extremely useful if testosterone could be
given on a prn (as needed) basis before sexual intercourse. Recently Tuiten et al [2000]
studied normal volunteer women with vaginal flow measures using photoplethysmography in
addition to questionnaire data on sexual arousal after exposure to erotic movies with pre
treatment of sublingual testosterone vs. placebo in a single dose sublingually of 0. 5mg.
Testosterone significantly enhanced vaginal blood flow response to the erotic movies and also
the subjective sexual interest, desire and arousal to the movies. The psychophysiological
effect was maximal 4 hours after the sublingual testosterone. Blood levels of 25nmol/L
testosterone, 10 times baseline, were maximal 10 minutes after sublingual delivery and
returned to baseline within 90 minutes.
This study suggested that it may be possible to give transdermal testosterone 4-8 hours
before intercourse in couples where the female partner suffers from low sexual interest or
desire and /or difficulties in arousal, but where the couple is able to plan intercourse
several hours in advance, which is possible in many couples, based on our clinical
experience. In such couples androgen could be given on a prn basis and the possibility of
side effects with long term use greatly reduced. We therefore propose such a study.
Methods The study will be done as a double-blind randomized crossover study. Women entering
the study will be pre-menopausal ages 21-40 with a diagnosis of hypo-active sexual disorder
by an experienced sexologist diplomate of the Israel Society for Sexual Therapy. Patients
will be accepted for study only if they can plan intercourse with their partner. Patients
unable to do so will be offered 3 sessions of counseling about sexual communication and those
still unable to plan intercourse after those 3 sessions will be excluded from the study.
Patients accepted for the study after written informed consent will be given 8 packets of
Testosteron Gel (Androgel) 50mg and shown how to spread the gel on the skin of the lower
abdomen or upper shoulders. They will be told that they can use the gel up to twice weekly
for one month. Patients will be instructed to spread the gel 4-8 hours before planned
intercourse. The patients will be instructed to shower to remove any remaining gel after
intercourse. After each intercourse they will fill out the Arizona Sexual Experiences Scale
(ASEX)- Female [McGahuey, et al. 2000]. At baseline and at the end of the month they will be
interviewed and rated for the month as a whole using the Sexual Function Questionnaire
(SFQ-V1) [Quirk, et al. 2002]. They will then be given a package of 8 placebo gels with the
same instruction and invited back after a month for another rating. Half of the women will
be given placebo and then switched over to active androgen.
We request permission to advertise on the internet and/or in newspapers for symptomatic
volunteers for the study.
Possible (but improbable due to the low doses and the prn use) side effects include: Increase
in total cholesterol, high density lipoprotein cholesterol, low density lipoprotein
cholesterol, triglycerides, fasting glucose and insulin; changes in blood counts and changes
in liver function tests (serum aspartate aminotransferase, serum glutamyltransferase, serum
albumin); hirsutism and acne, increase in facial hair or loss of hair; diarrhea, nipple and
breast enlargement or breast pains; headache; elevation of blood pressure, changes in mood or
aggressiveness. Slight local skin irritation or dryness of skin. However, as stated before,
these side effects are unlikely using prn treatment.
Dose: The recent study of Shifren et al [2000] used continuous transdermal patch and reached
blood levels of 3. 0nmoles/L (5x baseline) in post-menopausal women, with no side effects over
12 weeks. Goldstat et al [2003] looked at transdermal gel 10mg, which is applied daily but
washes off as the day wears on, for 12 weeks with no side effects in pre-menopausal women.
They reached blood levels of 2. 6nmoles/L (2. 5x baseline). Tuiten et al [2000] used
sublingual one time dose of 0. 5mg, reaching a peak blood level of 25nmoles/L (10x baseline)
at 10 minutes which returned to baseline within 90 minutes. We propose to minimize side
effects and maximize benefit by single application use of 50mg testosterone in transdermal
gel to be used only up to twice a week. Blood levels from this dose from Wang et al [2000]
should be about 20nmoles/L. Since patients are instructed to shower after intercourse, these
blood levels should exist for only 4-8 hours twice a week. Based on Tuiten et al [2000] a
short pulse of testosterone up to these levels is necessary to achieve psychophysiological
effects, and thus we request permission to use a dose of 50mg Androgel which would be too
high if used daily chronically in women.
Eligibility
Minimum age: 21 Years.
Maximum age: 40 Years.
Gender(s): Female.
Criteria:
Inclusion Criteria:
pre-menopausal females, hypoactive sexual disorder, age 21-40, able to plan intercourse
with partner -
Exclusion Criteria:
-
Locations and Contacts
Beersheva Mental Health Center, Beersheva, Israel
Additional Information
Starting date: April 2005
Ending date: April 2006
Last updated: May 26, 2008
|
