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VERDICT & SUMMARY
Testosterone patch
(Intrinsa®▼)
For the treatment of female hypoactive
sexual desire disorder
Committee’s Verdict: Category D
BNF: 6.4.2
The testosterone patch is not considered suitable for prescribing. Current clinical evidence for efficacy
is weak, based on short-term (24-week) trials using subjective outcomes. The size of benefit found was
small, with questionable clinical relevance and a large placebo effect. There is concern about potential
harmful effects of long-term use on breast tissue and the cardiovascular system (and endometrium if
used outside the product license).
Category D: cannot be recommended for prescribing because of inadequate evidence for efficacy and/or safety
MTRAC reviewed this drug because it is a new formulation with potential for prescribing in primary care.
Licensed indication
For the treatment of hypoactive sexual desire disorder
(HSDD) in bilaterally oophorectomised and
hysterectomised (surgically-induced menopause)
1
women receiving concomitant oestrogen therapy.
Background information
In the Diagnostic and Statistical Manual of Mental
Disorders, hypoactive sexual desire disorder (HSDD)
is defined as a persistent or recurrent deficiency or
absence of sexual fantasies and desire for sexual
activity.2 The American Urological Association
characterises clinical lack of desire as occurring when
a woman fails to feel desire at any stage during the
sexual episode, and defines HSDD as one
characterised by 'absent or diminished feelings of
sexual interest or desire, absent sexual thoughts or
fantasies, and a lack of responsive desire.
Motivations for attempting to become sexually
aroused are scarce or absent. Lack of interest goes
beyond a normal lessening with increasing age and
relationship duration'.3
There is debate whether lack of sexual desire is a
disorder or a normal state in some women. What is
generally agreed is that a lack of desire that causes
distress to the woman or problems in the relationship
with her partner is clinically important.4
In women, testosterone production is divided evenly
between the ovaries and the adrenal gland. Removal
of the ovaries during oophorectomy may lead to
testosterone deficiency and, in some women,
4
concomitant loss of libido.
A detailed history should be obtained from both
partners in the relationship to eliminate other factors
that may be affecting the woman’s desire for sex such
as painful intercourse or previous sexual trauma.
Psychological approaches such as cognitive
behavioural therapy or sex therapy may enable the
couple to focus their relationship in a more positive
direction.
October 2007
For the treatment of decreased libido in
perimenopausal women, testosterone has been used
as an adjunct to hormone replacement therapy.5,6 It is
available as an intramuscular injection or implant (50
to 100 mg every 4 to 8 months).6
The testosterone transdermal patch has recently been
licensed for the treatment of HSDD. The aim of
treatment is to replace testosterone in patients who
may have androgen deficiency as a result of removal
of the ovaries.
Clinical efficacy
Four double-blind, randomised, controlled trials7-10
compared the testosterone 300 µg/day patch with a
placebo patch in women who had undergone
surgically-induced menopause, were receiving a
stable dose of oestrogen, and expressed concern
about their loss of libido. One study also evaluated
patches delivering 150 µg and 450 µg of testosterone
per day.9 The studies were of 24 weeks’ duration and
involved 1,619 women with a mean age of about 49
years.
The primary outcome measure in the studies was the
change in the number of satisfying sexual episodes
during the last four weeks of treatment compared with
baseline as reported in the Sexual Activity Log, a
weekly diary of sexual activity kept by participants. In
two studies,9,10 the sexual desire domain of the Profile
of Female Sexual Function (PFSF) was also used as
a primary endpoint. Both outcome measures were
developed and validated by the manufacturer of the
testosterone patch.
The PFSF7 is a 37-item questionnaire measuring
seven different domains of sexual function: sexual
desire, sexual pleasure, sexual arousal, orgasm,
sexual responsiveness, lessening of sexual concerns
and sexual self-image. Scores from the domains are
summed and converted to a scale (0 to 100).
Results from three studies7-9 showed that the increase
in the total number of satisfying sexual episodes in a
four-week period was significantly greater for
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testosterone-treated patients than placebo-treated
patients (an average increase of about two episodes
per four-week period with testosterone treatment
compared with about one episode with placebo, from
a baseline of two to four episodes in four weeks).
There was no significant difference compared with
placebo in the fourth study (which may have been
underpowered for the primary endpoint).10 Doses of
150 µg and 450 µg of testosterone per day showed no
significant difference compared with placebo for this
outcome.9 There was a large placebo response in the
trials; 46% of patients on testosterone vs. 35% on
placebo were responders (i.e. had an increase from
baseline of at least one satisfying sexual episode per
four-week period). Fifty-four percent of patients on
testosterone were non-responders.5
In all four studies, there was a significantly greater
improvement with testosterone treatment for the
sexual-desire domain of the PFSF compared with
placebo after 24 weeks’ treatment (increases of 6 or 7
points more than placebo on a 100-point scale). The
differences for women using 150 µg and 450 µg
patches were not statistically significant compared
with placebo.9 Significantly greater improvements
after 24 weeks’ treatment were reported for
testosterone-treated women compared with placebo in
the remaining six domains of the PFSF in two
studies7,8 in five domains in one study10 and in one
9
domain (sexual arousal) in the final study.
Adverse effects
The most commonly reported adverse events were
application-site reactions, headaches, upper
respiratory tract infections and acne. None of the
trials reported any significant differences in the
incidence of androgenic side effects between
testosterone- or placebo-treated women; the
incidences were 18% in testosterone-treated women
and 14% in placebo-treated women.
The EMEA’s Committee for Medicinal Products for
Human use (CHMP) expressed concern about the
lack of long-term safety data, especially with regard to
potential harmful effects on the breast, the
cardiovascular system and, in the case of unlicensed
use in women with a uterus, the endometrium.11 The
manufacturer was requested to provide a Risk
Management Plan to address the need for longer-term
safety data. As part of the Plan, prescribing will be
monitored. Off-license use in women with natural
menopause and in those not taking additional
hormone replacement therapy will be discouraged.11
Additional information
• The recommended daily dose of testosterone is
300 µg via a patch applied to the abdomen twice
weekly.
• The response to treatment should be evaluated
within 3 to 6 months of initiation, and treatment
discontinued if no meaningful benefit is reported.
• At current prices, a year’s treatment with the
testosterone 300 µg/day transdermal patch costs
£364.
References
1.
Procter and Gamble Pharmaceuticals UK Ltd.
Intrinsa transdermal patch. Summary of Product
Characteristics. 2007.
http://www.emc.medicines.org.uk/
2. Diagnostic and Statistical Manual of Mental Disorders
DSM-IV-R. 4th ed. Washington DC: American
Psychiatric Association; 2003.
3. Basson R. Sexual desire and arousal disorders in
women. N Engl J Med 2006;354:1497-1506.
4. Butcher J. ABC of Sexual Health. Female sexual
problems I: Loss of desire - what about the fun? BMJ
1999;3318:41-43.
5. UK Medicines Information Service. Testosterone
®
Transdermal Patch (Intrinsa ) for female hypoactive
sexual desire disorder. 07/03a. UKMi. 2007.
http://www.nelm.nhs.uk/Documents/TestosteroneNM
PRevisedJun07.pdf?id=578766
6. Anon. Male sex hormones and antagonists. British
National Formulary. 53 ed. 2007. pp. 389-391.
7. Simon J, Braunstein G, Nachtigall L et al.
Testosterone patch increases sexual activity and
desire in surgically menopausal women with
hypoactive sexual desire disorder. J Clin Endocrinol
Metab 2005;90:5226-5233.
8. Buster JE, Kingsberg SA, Aguirre O et al.
Testosterone patch for low sexual desire in surgically
menopausal women: A randomised trial. Obstet
Gynecol 2005;105:944-952.
9. Braunstein G, Sundwall DA, Katz M et al. Safety and
efficacy of a testosterone patch for the treatment of
hypoactive sexual desire disorder in surgically
menopausal women. Arch Intern Med
2005;165:1582-1589.
10. Davis SR, van der Mooren MJ, van Lunsen RHW et
al. Efficacy and safety of a testosterone patch for the
treatment of hypoactive sexual desire disorder in
surgically menopausal women: a randomised,
placebo-controlled trial. Menopause 2006;13:387396.
11. European Medicines Agency. European Public
Assessment Report: Intrinsa. EMEA. 2007.
http://www.emea.europa.eu/humandocs/PDFs/EPAR/
intrinsa/063406en6.pdf <accessed 4/10/2007>
Launch date: April 2007
Manufacturer: Procter & Gamble Pharmaceuticals UK Ltd
EU/1/06/352/002
WARNING: This sheet should be read in conjunction with the Summary of Product Characteristics
This guidance is based upon the published information available in English at the time the drug was considered. It remains
open to review in the event of significant new evidence emerging.
MTRAC can be contacted at the Dept. of Medicines Management, Keele University, Keele, Staffs ST5 5BG
Tel: 01782 584131 Fax: 01782 713586 Email: [email protected] Web: www.mtrac.co.uk
Relevant NICE guidance was not available at time of issue of this verdict
Date: October 2007
©Midlands Therapeutics Review & Advisory Committee
VS07/20