Testosterone in Female Hypoactive Sexual Desire Disorder
Testosterone in Female Hypoactive Sexual Desire Disorder
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.
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.
Inclusion Criteria:

 pre-menopausal females, hypoactive sexual disorder, age 21-40, able to plan intercourse
 with partner -

 Exclusion Criteria:

 -