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Menopause
Matters
Testosterone Therapy in
Postmenopausal Women
Jan L. Shifren, MD
Declining sexual interest, desire, and
activity are frequent complaints among postmenopausal women. Causes
of declining sexual interest and treatment options, including testosterone,
are a target of research in this population.
In 2005, The North American Menopause Society published an evidence-based
position statement addressing the role of testosterone therapy in
postmenopausal women.1
The Society enlisted experts to review the literature, compile supporting
statements, and present recommendations. This paper presents some
of those findings.
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PHYSIOLOGY
The ovaries account for approximately 50% of circulating testosterone,
either directly or via peripheral conversion of ovarian precursors.
Women who have experienced menopause have lower levels of testosterone
than do premenopausal women. This decrease is gradual, however,
and likely results from the decline in ovarian and adrenal function
that occurs with aging. Although not all studies agree, the postmenopausal
ovary appears to produce some testosterone throughout life. Thus,
bilateral oophorectomy—even after menopause—can significantly
decrease testosterone levels.
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SEXUAL EFFECTS
The relationship between endogenous
testosterone levels and sexual
function in postmenopausal women
has not been clearly established, with
observational studies yielding varying
results. The link between exogenous
testosterone and sexual function is
clearer. Although evidence from well
designed studies is limited, randomized,
controlled trials find consistent
evidence of improvements in sexual
desire, responsiveness, and frequency
when testosterone is added to estrogen
therapy (ET).
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OTHER EFFECTS
In addition to sexual function,
testosterone therapy has been evaluated
for its effect on several other
endpoints, including bone mineral
density (BMD), well-being, menopausal
symptoms, body composition,
and cognition. Despite some
positive results in the areas of BMD
and well-being, data are inadequate
to support recommending
testosterone therapy for any of
these conditions.
It is not known whether testosterone
therapy increases the risk for
breast cancer, cardiovascular disease
(CVD), or thromboembolic
events. Nevertheless, testosterone is
generally not recommended for use
in women with breast or uterine
cancer, CVD, or liver dysfunction.
Additionally, the effects of testosterone
therapy in postmenopausal
women not receiving concomitant
ET have not been determined.
Other adverse effects of testosterone
therapy may include increased
facial hair and acne. The
likelihood of these side effects is
low when testosterone levels are
maintained within the normal female
range.
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CLINICAL EVALUATION
Postmenopausal women presenting with complaints of decreased sexual
desire, arousal, or response associated with personal distress may
be candidates for testosterone therapy. In the clinical evaluation,
the primary goal is to rule out alternative causes of the patient's
sexual concerns via a comprehensive psychosexual and psychosocial
history, medical history (including medications that may have an
impact on sexual function), and physical examination. Laboratory
tests may include thyroid-stimulating hormone levels, a complete
blood cell count, prolactin values, and/or pelvic ultrasonography.
The differential diagnosis for decreased libido and sexual response
is extensive, and includes fatigue, stress, underlying depression,
antidepressant side effects, vaginal atrophy, and partner relationship
or performance problems. Physical, psychological, emotional, and
relationship factors have a significant impact on sexual function
and must all be considered during the evaluation of a sexual problem.2
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LABORATORY
EVALUATION
Several laboratory tests are available
to measure testosterone levels
in women, including assays that
evaluate total and free hormone.
However, the accuracy of commercially
available testosterone assays
has caused some concern, particularly
regarding their sensitivity at
the low levels typical in postmenopausal
women. Most such assays
were designed to measure
testosterone levels in men, which
are approximately 10-fold higher
than levels in women. Testosterone
levels should not be used in determining
the cause of a sexual problem.
Most postmenopausal women
have low testosterone levels, but
low levels do not necessarily result
in sexual dysfunction. Nevertheless,
total testosterone assays can be
clinically useful to rule out a hyperandrogenic
state prior to initiating
testosterone therapy, or secondary
to treatment.
The simplest and most readily available clinical estimate of free
testosterone is the free testosterone (T) index, calculated from
total testosterone and sex hormonebinding globulin (SHBG), which
binds to testosterone. The Sodergard equation for free T is also
useful, incorporating total testosterone, SHBG, and albumin.3
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THERAPY
A few prescription testosteronecontaining
products have been approved
by the US Food and Drug
Administration (FDA) for use in
both women and men, but their
use to treat sexual desire disorders
in postmenopausal women is off-label.
In addition, products approved
for men may result in unacceptably
high testosterone levels when used
in women.
Custom-compounded testosterone
formulations are also available
by prescription, but these preparations
are not subject to the stringent
quality-control standards of
FDA-approved products. As a result,
they may have inconsistent
content and bioavailability. Also,
clinical trials have not evaluated
their safety or efficacy for any indication,
including improvement of
female sexual function.
Patches delivering low testosterone doses (150 to 300 mcg/d) are
under investigation for use in women. Clinical trials indicate that
a 300-mcg/d dose for 3 to 6 months is generally safe and effective
for the treatment of hypoactive sexual desire disorder in women
with surgically induced menopause who are receiving concomitant
ET.4-6 Any discussion
of testosterone therapy should include a full explanation of its
potential benefits and risks. Women should understand that data
on safety and efficacy are limited, including data on long-term
use, or use without concomitant ET. In addition, they must be informed
that none of the common testosterone therapies are FDA-approved
for treating female sexual dysfunction, so that such use is off-label.
The physician is advised to document this discussion in the medical
record.
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MONITORING
Drug testosterone therapy patient
monitoring includes subjective assessment
of sexual desire, response,
and satisfaction. Women should also be evaluated for potential adverse
effects (eg, acne, hirsutism)
that may be signs of excess dosing.
Establishing baseline levels for
lipids and liver function may be
prudent before initiating testosterone
therapy, particularly with
oral testosterone. Treatment should
be reduced or stopped if adverse
events occur.
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CONCLUSION
Postmenopausal sexual function
can be problematic, involving both
physical and psychological factors.
Treatment should likewise be
multifactorial, with careful assessment
of well-being and response
to therapies.
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Jan L. Shifren, MD, is assistant professor
of Obstetrics, Gynecology, and Reproductive Biology at Harvard Medical
School; and director of the Vincent Menopause Program at Massachusetts
General Hospital, both in Boston, Mass. She is also chair of the
2005-2006 Consumer Education Committee of The North American Menopause
Society. Disclosures are available upon request.
References
- The North American Menopause Society. The role
of testosterone therapy in postmenopausal women: position statement
of The North American Menopause Society. Menopause. 2005;
12(5):496-511.
- Basson R, ed. Update on sexuality at menopause
and beyond: normative, adaptive, problematic, dysfunctional. Menopause.
2004;11(2 pt 2):707-784.
- Sodergard R, Backstrom T, Shanbhag V, Carstensen
H. Calculation of free and bound fractions of testosterone and
estradiol-17 beta to human plasma proteins at body temperature.
J Steroid Biochem. 1982;16(6):801-810.
- Braunstein GD, 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: a randomized,
placebo-controlled trial. Arch Intern Med. 2005;165(14):
1582-1589.
- Buster JE, Kingsberg SA, Aguirre O, et al. Testosterone
patch for low sexual desire in surgically menopausal women: a
randomized trial. Obstet Gynecol. 2005;105(5 pt 1):944-952.
- Shifren JL, Braunstein GD, Simon JA, et al.
Transdermal testosterone treatment in women with impaired sexual
function after oophorectomy. N Engl J Med. 2000;343(10):682-688.
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