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Transdermal testosterone treatment in women with impaired
sexual function after oophorectomy.
BACKGROUND: The ovaries provide approximately half the circulating testosterone
in premenopausal women. After bilateral oophorectomy, many women report impaired
sexual functioning despite estrogen replacement. We evaluated the effects of
transdermal testosterone in women who had impaired sexual function after surgically
induced menopause. METHODS: Seventy-five women, 31 to 56 years old, who had undergone
oophorectomy and hysterectomy received conjugated equine estrogens (at least
0.625 mg per day orally) and, in random order, placebo, 150 microg of testosterone,
and 300 microg of testosterone per day transdermally for 12 weeks each. Outcome
measures included scores on the Brief Index of Sexual Functioning for Women,
the Psychological General Well-Being Index, and a sexual-function diary completed
over the telephone. RESULTS: The mean (+/-SD) serum free testosterone concentration
increased from 1.2+/-0.8 pg per milliliter (4.2+/-2.8 pmol per liter) during
placebo treatment to 3.9+/-2.4 pg per milliliter (13.5+/-8.3 pmol per liter)
and 5.9+/-4.8 pg per milliliter (20.5+/-16.6 pmol per liter) during treatment
with 150 and 300 microg of testosterone per day, respectively (normal range,
1.3 to 6.8 pg per milliliter [4.5 to 23.6 pmol per liter]). Despite an appreciable
placebo response, the higher testosterone dose resulted in further increases
in scores for frequency of sexual activity and pleasure-orgasm in the Brief index
of Sexual Functioning for Women (P=0.03 for both comparisons with placebo). At
the higher dose the percentages of women who had sexual fantasies, masturbated,
or engaged in sexual intercourse at least once a week increased two to three
times from base line. The positive-well-being, depressed-mood, and composite
scores of the Psychological General Well-Being Index also improved at the higher
dose (P=0.04, P=0.03, and P=0.04, respectively, for the comparison with placebo),
but the scores on the telephone-based diary did not increase significantly. CONCLUSIONS:
In women who have undergone oophorectomy and hysterectomy, transdermal testosterone
improves sexual function and psychological well-being.
N Engl J Med . 2000 Sep 7;343(10):682-8
Androgen replacement in women: a commentary.
There is increasing evidence to suggest that many postmenopausal women experience
symptoms alleviated by androgen therapy and that such symptoms may be secondary
to androgen deficiency. Affected women complain of fatigue, low libido, and
diminished well-being, symptoms easily and frequently attributed to psychosocial
and environmental factors. When such symptoms occur in the setting of low circulating
bioavailable testosterone, testosterone replacement results in significant
improvement in symptomatology and, hence, quality of life for the majority
of women. Whether the apparent therapeutic effects of testosterone replacement
are mediated by testosterone and its metabolite 5alpha- dihydrotestosterone
or are a consequence of aromatization to estrogen is not known. Despite the
paucity of data regarding its effects, inclusion of testosterone in postmenopausal
hormone replacement regimens is not uncommon and is likely to become more widespread
with the availability of preparations developed specifically for women. Other
novel and even more controversial potential indications for androgen therapy
in women are currently being evaluated. These include use in women with premature
ovarian failure, premenopausal androgen deficiency symptoms, postmenopausal
and glucocorticosteroid-related bone loss, alleviation of wasting syndrome
secondary to human immunodeficiency virus infection, and management of premenstrual
syndrome. The aim of this commentary is to very briefly review the rationale
for the use of testosterone in women, create awareness of some of the therapeutic
options available in various countries, and stimulate discussion of this important
aspect of women's health.
J Clin Endocrinol Metab. 1999 Jun;84(6):1886-91
Androgens and female sexuality.
An accumulating body of data indicates that many women experience a cluster
of symptoms that are responsive to testosterone treatment and may be due to
androgen deficiency. Characteristically, affected women complain of low libido,
persistent fatigue, and diminished well-being and are found to have low circulating
bioavailable testosterone. Whether the apparent therapeutic effects of testosterone
are mediated via the androgen receptor or as a consequence of metabolism to
estrogen is not known. Despite the lack of understanding of the mechanism(s)
by which testosterone may enhance libido, the prescription of testosterone
to women in a variety of formulations is becoming increasingly popular. This
article provides an overview of the rationale for testosterone therapy in women,
offers a broad definition of androgen deficiency in women based on the clinical
experience of the author, and outlines the currently available options and
potential risks of testosterone replacement in women.
J Gend Specif Med. 2000 Jan-Feb;3(1):36-40
Testosterone enhances estradiol's effects on postmenopausal bone density and
sexuality.
To investigate the role of androgens in increasing bone density and improving
low libido in postmenopausal women, we have studied the long-term effects of
estradiol and testosterone implants on bone mineral density and sexuality in
a prospective, 2 year, single-blind randomised trial. Thirty-four postmenopausal
volunteers were randomised to treatment with either estradiol implants 50 mg
alone (E) or estradiol 50 mg plus testosterone 50 mg (E&T), administered
3-monthly for 2 years. Cyclical oral progestins were taken by those women with
an intact uterus. Thirty-two women completed the study. BMD (DEXA) of total
body, lumbar vertebrae (L1-L4) and hip area increased significantly in both
treatment groups. BMD increased more rapidly in the testosterone treated group
at all sites. A substantially greater increase in BMD occurred in the E&T
group for total body (P < 0.008), vertebral L1-L4 (P < 0.001) and trochanteric
(P < 0.005) measurements. All sexual parameters (Sabbatsberg sexual self-rating
scale) improved significantly in both groups. Addition of testosterone resulted
in a significantly greater improvement compared to E for sexual activity (P < 0.03),
satisfaction (P < 0.03), pleasure (P < 0.01), orgasm (P < 0.035) and
relevancy (P < 0.05). Total cholesterol and LDL-cholesterol fell in both
groups as did total body fat. Total body fat-free mass (DEXA, anthropometry,
impedance) increased in the E&T group only. We concluded that in postmenopausal
women, treatment with combined estradiol and testosterone implants was more
effective in increasing bone mineral density in the hip and lumbar spine than
estradiol implants alone. Significantly greater improvement in sexuality was
observed with combined therapy, verifying the therapeutic value of testosterone
implants for diminished libido in postmenopausal women. The favourable estrogenic
effects on lipids were preserved in women treated with T, in association with
beneficial changes in body composition.
Maturitas . 1995 Apr;21(3):227-36
Exogenous androgens influence body composition and regional body fat distribution
in obese postmenopausal women--a clinical research center study.
Abdominal fat distribution is influenced by androgen levels in both
men and women. The purpose of this study was to assess the effects
on fat distribution of administering nandrolone decanoate (ND; an anabolic
steroid with weak androgenic activity) or spironolactone (SP; an antiandrogen)
in obese postmenopausal women. The design was a randomized, placebo-controlled,
9-month trial with simultaneous calorie restriction for weight loss.
Women in all three groups lost comparable amounts of weight, but the
ND-treated women gained lean mass relative to the other two groups
(P < 0.0005) and lost more body fat than women in the SP
group (P < 0.01). The resting metabolic rate also increased slightly in
the ND group. ND treatment produced a gain in visceral fat, as determined by
computed tomography scan, and a relatively greater loss of sc abdominal fat.
SP-treated women lost significantly less sc fat than the other two groups.
Serum cholesterol decreased in the placebo group, but increased slightly in
the other two groups (significant for SP vs. placebo, P < 0.05). High density
lipoprotein cholesterol decreased significantly in the ND-treated women. There
were no significant changes in fasting glucose or insulin sensitivity. We conclude
that administration of exogenous androgens modulates body composition in obese
postmenopausal women and independently affects visceral and sc abdominal fat.
J Clin Endocrinol Metab . 1996 Jun;81(6):2198-203
Testosterone deficiency: a key factor in the increased cardiovascular
risk to women following hysterectomy or with natural aging?
The ovaries are a critical source not only of estrogen but also of
testosterone. On removal of the uterus, even in instances where ovaries
have been spared, their function can be compromised. Women who have
had a simple hysterectomy (ovaries remaining intact), even if treated
postsurgically with supplementary estrogen, have three times the
risk of cardiovascular disease compared with women who have not had
a hysterectomy. In men, testosterone has been demonstrated to have
beneficial fibrinolytic effects and beneficial effects on blood vessel
endothelium, in blood sugar and insulin metabolism, and in maintaining coronary
artery circulation. Studies on the potential cardiovascular protective effects
of physiologic levels of testosterone in women are critically needed. Restoring
a physiologic level of testosterone to women after hysterectomy not only
can improve quality of life in terms of sexual libido, sexual pleasure,
and sense of well-being but also can build bones--and may be a key
to protecting cardiovascular health. Women developing testosterone
deficiency as a consequence of natural aging/menopause may similarly
benefit from physiologic testosterone supplementation. J Womens Health . 1998 Sep;7(7):825-9
Serum sex hormone levels after menopause and subsequent breast cancer.
BACKGROUND: High levels of androgens and estrogens have been reported to be
associated with breast cancer. However, the multiplicity of factors that
influence hormone levels and methodologic issues complicate the study of
the relationship between steroid sex hormones and breast cancer. PURPOSE:
Using an improved study design, we assessed prospectively the relationship
between the principal steroid sex hormones in serum and the subsequent occurrence
of invasive breast cancer in postmenopausal women. METHODS: Four thousand
fifty-three healthy postmenopausal women aged 40-69 years, were enrolled
from June 1987 through June 1992 in a prospective investigation of hormones
and diet in the etiology of breast tumors (ORDET study) as part of a larger
volunteer cohort of 10 788 premenopausal and postmenopausal women from Varese
Province, northern Italy. At recruitment, blood samples were taken between
8:00 AM and 9:30 AM (after overnight fasting), and sera were preserved in
-80 degree Celsius freezers. Women who had received hormone treatment in
the 3 months prior to enrollment, who had bilateral ovariectomy, or who had
a history of cancer or liver disease were not recruited. Twenty-five women
in the final eligible cohort of postmenopausal women developed histologically
confirmed, invasive breast cancer during the first 3.5 years of follow-up
for the cohort (13 537 women-years). For each case subject, four control
subjects were randomly chosen after matching for factors possibly affecting
hormone preservation in serum. One case subject and eight control subjects
were excluded because premenopausal hormonal patterns were found; thus, after
also excluding the four control subjects matched to the ineligible case subject,
we included 24 case and 88 control subjects. In the spring of 1994, stored
sera of case and control subjects were assayed in a blinded manner for dehydroepiandrosterone
sulfate and estradiol (E2) by in-house radioimmunoassay and for total and
free testosterone and sex hormone-binding globulin by commercially available
nonextraction iodination kits. Mean differences in risk factors were tested
by analysis of variance for paired data. Relative risks (RRs) were estimated
by conditional logistic regression analysis. All P values resulted from two-sided
tests. RESULTS: Age-adjusted mean values of total testosterone, free testosterone,
and E2 were significantly higher in case subjects than in control subjects:
total testosterone, 0.34 ng/mL versus 0.25 ng/mL (P<.001); free testosterone,
1.07 pg/ml versus 0.77 pg/mL (P= .006); and E2, 25 pg/mL versus 22 pg/mL
(P= .027). Age-adjusted RRs for breast cancer in increasing tertiles were
as follows: for total testosterone, 1.0, 4.8, and 7.0 (P for trend =.026);
for free testosterone, 1.0, 1.8, and 5.7 (P for trend=.005); and for total
E2, 1.0, 7.1, and 5.5 (P for trend= .128). CONCLUSIONS AND IMPLICATIONS:
This prospective study provides further evidence in support of the already
established association between elevated estrogen levels and breast cancer.
Even more importantly, it provides new evidence that high serum testosterone
levels precede breast cancer occurrence.
J Natl Cancer Inst . 1996 Mar 6;88(5):291-6 |