Androgen Deficiency in Women with Hypopituitarism
The effects of low testosterone levels in men have been well understood
for some time and include a decrease in libido, bone density and
muscle mass (1,2). Circulating androgen levels in healthy young
women are a fraction of those found in men, with testosterone levels
approximately one tenth of male levels, and it is not known whether
relative androgen deficiency has similar clinical implications for
women as for men.
In women, the androgens testosterone and androstenedione are secreted
by the ovaries and adrenal glands (3,4). In contrast, DHEAS is secreted
almost exclusively by the adrenals. Because hypopituitarism often
results in reduced ovarian and/or adrenal function, researchers
here at the Neuroendocrine Unit at Massachusetts General Hospital
hypothesized that women with hypopituitarism might have reduced
androgen levels. Therefore, fasting testosterone, free testosterone,
androstenedione and DHEAS levels were measured at 8:00 am on three
days during one month in 55 women with hypopituitarism, defined
as secondary hypogonadism and/or hypoadrenalism. Four subsets of
hypopituitary women were studied, including women of reproductive
and post-menopausal age and those receiving or not receiving estrogen
therapy. The majority of patients studied had a history of a pituitary
tumor and had undergone either surgery or radiation therapy, while
the etiology of the hypopituitarism in other patients included craniopharyngiomas,
brain tumors and hypophysitis. Four subsets of women with normal
pituitary function were also recruited to serve as appropriate controls
for the four subsets of women with hypopituitarism. Healthy women
of reproductive age not taking estrogen were studied in the early
follicular phase, midcyle and mid-luteal phase of the menstrual
Preliminary data suggest that androgen levels are markedly decreased
in women with hypopituitarism compared with women who have normally
functioning pituitary glands (5). In all subsets of hypopituitary
women, all androgens studied - testosterone, free testosterone,
androstenedione and DHEAS - were markedly reduced, regardless of
age or estrogen therapy. In addition, the midcycle increases seen
in testosterone, free testosterone and androstenedione in women
with normal pituitary and ovarian function were absent in the women
with hypopituitarism. Furthermore, androgen levels in many women
with hypopituitarism were undetectable by current assays for at
least one androgen for the majority of women. Figure 1 shows body
mass index (BMI).
The black bars show women with hypopituitarism. The white bars
show controls. *
Figure 1. Figure 1. Free testosterone levels in
18 women of reproductive age with hypopituitarism compared with
18 age- and BMI-matched controls studied in the early follicular
(EF), midcycle (MC) and mid-luteal (ML) phases of the menstrual
, women with hypopituitarism.
, controls. *, p<0.05
The clinical implications of the hypoandrogenemia detected in women
with hypopituitarism and indications, if any, for therapy at this
time have not been established. However, many women with hypopituitarism
suffer from osteopenia, obesity and decreased libido (6-8). In hypogonadal
men, androgen replacement has been well documented to result in
an increase in bone density, decrease in fat mass and an increase
in libido (1,9,10). Therefore, androgen replacement therapy may
prove efficacious in women with hypopituitarism. However, physiologic
androgen replacement doses for women would be significantly lower
than those administered safely to men, and no such preparation is
yet commercially available.
Most studies of androgen therapy in women thus far have used supraphysiologic
androgen doses or have not been randomized, controlled trials. However,
a few cross-sectional studies demonstrate correlations between androgen
levels and bone density or libido in women. Results from the few
randomized, controlled studies are promising in terms of effects
of androgens on bone formation and bone density (11-15). Further
study is needed to determine whether low doses of androgens would
result in similar benefits to libido, bone mineral density and body
composition in women with hypopituitarism.
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E, Klibanski A. 1996 Increase in bone density and lean body mass
during testosterone administration in men with acquired hypogonadism.
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- Miller K, Sesmilo G, Schiller A, Burton S, Klibanski A. 2000
Abstract #2173: Androgen deficiency in women with hypopituitarism.
The Endocrine Society's 82nd Annual Meeting, Toronto, Canada.
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