Download Evaluating medications for women

Evaluating medications for women
with female sexual dysfunction
Laura S. Dalton, DO
The only medications currently approved
for a specific sexual dysfunction are phosphodiesterase type-5 inhibitors, which are
used to treat men with erectile dysfunction.
Any medications used for female sexual dysfunction (FSD) are used off-label. In the
past few years, pharmaceutical companies
have presented applications for several FSD
medications to the U.S. Food and Drug
Administration (FDA). However, the FDA
has denied approval for these medications,
either because of a paucity of long-term safety data or because of a failure to demonstrate
statistically significant improvement in
symptoms (ie, “satisfying sexual events”)
compared with placebo.
Sexual dysfunction is not life-threatening and does not produce a serious impact
on patients’ physical health. Thus, to receive FDA approval for sexual dysfunction,
medications must meet the highest levels
of quality of evidence in efficacy and safety.1,2 My purpose in this article is for it to
serve as a review of medications that are either already available for FSD or under
investigation for FSD.
Testosterone
Testosterone supplementation has been extensively studied in postmenopausal women,
though it remains unapproved by the FDA
for use in women with FSD.1,3 A twiceweekly testosterone patch designed for use
in women has shown efficacy in women with
hypoactive sexual desire disorder (HSDD),
but availability is pending and dependent
on long-term safety data.4-8 Interestingly,
studies on use of the testosterone patch for
FSD have suggested efficacy at moderate
doses but little improvement at higher doses.9
Testosterone products formulated for
men should not be used to treat women
with FSD, because such products result in
extremely high physiologic levels of testos-
16
terone in women and increased risk of androgenic adverse effects, such as hirsutism,
voice changes, acne, and clitoromegaly. They
also have an adverse impact on lipid levels
in women. Compounded 1% testosterone
cream in petrolatum has been used historically as a treatment for lichen sclerosis et
atrophicus, and it may be appropriate for
some women if applied nightly at a dose of
0.5 g. However, although gynecologists may
feel comfortable prescribing this cream, it
should be kept in mind that no safety or
efficacy data exist for this compound’s use
in managing FSD.
Hormone therapy
Although anecdotal evidence and some study
data suggest that hormone therapy may
improve sexual desire in women, such results were not observed in the Women’s
Health Initiative (WHI) study.10 In that randomized controlled trial, women were asked
about their overall sexual function—but not
desire—and results were tabulated using a
Likert scale. The WHI investigators found
no differences in sexual function between
women taking conjugated equine estrogen/
medroxyprogesterone acetate and women
taking placebo.10
It’s important to note that the WHI did
not measure satisfying sexual events,10
which are now considered the primary endpoint for treatment of patients with FSD.
Furthermore, the WHI did not screen
study participants for FSD, and many of
the participants were older than the typical woman with FSD.10
For patients requiring postmenopausal
hormone therapy, formulations of esterified
estrogens and methyltestosterone may be used
to increase testosterone levels.11,12 These
products are not FDA-approved for FSD,
though several studies have shown that they
can improve sexual functioning in women.13, 14
Vaginal estrogen therapy—including
creams, tablets, and rings—can be used
successfully to improve atrophic changes
in postmenopausal women. Correcting
these changes can reduce vaginal discomfort and improve sensation. Local estrogen
therapy does not produce the potentially
harmful blood levels of estrogen that can
occur with systemic therapy, and, thus, it
is viewed as less risky.15
Other pharmacologic agents
Laboratory studies and clinical observations
have shown that changes in neurotransmitter activity can cause changes in
sexual desire. In general, serotonergic activity is inhibitory and dopaminergic activity
is facilitatory to sexual desire.16 An application to use flibanserin (a 5-HT2 receptor
antagonist and 5-HT1 receptor agonist) to
modulate neurotransmitter levels in premenopausal women with low sexual desire
was recently presented to the FDA. The regulatory agency determined, however, that
the drug did not meet criteria for efficacy.
The FDA also cited evidence of statistically
significant adverse events associated with
flibanserin, including depression, syncope,
fainting, and accidental injury.17-21 The
manufacturer has since withdrawn its application for FDA approval of flibanserin.22
Monoamine oxidase inhibitors, tricyclic
antidepressants, and selective serotonin reuptake inhibitors (SSRIs) have all been
shown to inhibit sexual activity in women.
Antidepressant-induced FSD may be improved by changing medications. To
manage SSRI-related orgasmic dysfunction,
some physicians use a short-acting SSRI
that a patient can skip for a weekend. This
approach is anecdotally effective.
Bupropion hydrochloride has norepinephrine and dopamine reuptake inhibition
effects and has been shown to improve sexual satisfaction, arousal, and orgasm.23,24
This drug may be considered as an alternative medication for women in whom FSD
develops with use of SSRIs for depression.
Sildenafil citrate, approved for male
erectile dysfunction, has been studied extensively in women. Results are inconclusive.
Although an off-label use, antidepressant-induced sexual desire problems in women have
improved with episodic use of sildenafil
(50mg) taken one hour before sexual activity.25
Other studies have shown some success in
using sildenafil for women with sexual arousal
disorder, including postmenopausal women
and even asymptomatic women.25-28
Local creams and gels are available to
improve sensation of the external genitalia.
For example, a blend of over-the-counter
herbs and vitamins marketed as “feminine
massage oil” has been demonstrated to result in improvement in satisfaction and level
of interest in women with disorders of sexual desire and arousal.29,30 Other kinds of
over-the-counter creams or gels lack clinical
data establishing their efficacy over placebo.
Nonpharmacologic therapy
An FDA-approved clitoral suction device
can be used to cause clitoral vascular engorgement. Studies have shown that this
device can cause improvement in arousal,
genital swelling, vaginal lubrication, and
enhancement of orgasm.31-33 Originally
recommended for use immediately prior
to sexual activity, the device is now recommended for use three to four times per week
independent of sexual activity to improve
genital blood flow and sensation. The
device is a prescription item that is available via the Internet.
Final notes
There are no FDA-approved pharmacologic
treatments for FSD—including HSDD, orgasmic dysfunction, or arousal disorder.
Many medications, especially neurotropic
drugs, migraine preventatives, and antidepressants can induce sexual dysfunction,
especially HSDD and orgasmic dysfunction.
Several medications have been studied
for use in women with FSD, with varying
results. Most of these studies have had small
sample sizes and varying endpoints. None
of the studies measured effects of the medications on sexual satisfaction. Testosterone
is known to increase sexual desire in
women, though formulations designed for
men should not be used for women.
Knowledge about the role of estrogen therapy in menopausal women remains limited.
Hormone therapy is FDA-approved only
for the treatment of women with menopausal syndrome.
Physicians should consider off-label
treatments only for well-selected patients
and after thorough discussion of the risks
and benefits with these patients. We can
look forward to continued research and development of medications to help women
with the distressing disorder of FSD.
17
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Laura S. Dalton, DO, is a past president
of the American College of Osteopathic
Obstetricians and Gynecologists, clinical
assistant professor of obstetrics and gynecology,
and medical director at the Virtua Center
for Women. Dr. Dalton can be reached
via e-mail at [email protected].