Testosterone's Impact on Postmenopausal Women and Breast Cancer
By Janna Gordon, RPh, MBA
brought to you by Bellevue Pharmacy, a ProjectAWARE
Loss of libido, fatigue, and anorgasmia are common testosterone
related symptoms women experience as their natural production of
hormones starts to decline during perimenopause and menopause. The
loss of testosterone is often a concern for patients and their physicians,
and many are asking, "Should testosterone be used as supplementation
in postmenopausal patients?" Additionally, there is worry with
the effects of testosterone on women with breast cancer.
Testosterone is an androgen or male hormone found in low levels
in the female body. It is a steroid produced in the ovaries, the
adrenal gland, and from conversion of other steroid hormones, such
as androstenedione and dehydroepiandrosterone (DHEA).1,2,3
Testosterone’s role in the body is to build muscle and promote
muscle tone, increase libido, strengthen bone and in some will improve
mood and metabolism. Testosterone levels typically decline as we
age due to declining ovarian and adrenal function.2 Another
possible driver of decreased testosterone is an elevated level of
a binding protein called sex hormone-binding globulin (SHBG). SHBG
binds to both estradiol and testosterone and inactivates the function
of these hormones while they are bound to it. An elevated level
of SHBG lowers the bioavailability of testosterone and can be an
issue for patients on hormone replacement therapy because oral estrogen
therapy has been associated with increases in SHBG.2,3
While currently there is not a commercially available testosterone
supplement for women, supplementing a women’s testosterone
level into a normal range has been shown to improve their sexual
enjoyment and libido.4 Numerous women will also testify
to the positive effects they experience once their testosterone
and other hormone levels are returned to a normal range with hormone
When evaluating testosterone’s impact on breast cancer, it
is unclear if testosterone is a singular causative agent or if breast
cancer is a result of other hormonal stimulation such as estrogens
or synthetic progestins. Several clinical studies have attempted
to answer this question with results suggesting that there is more
to the equation than testosterone. A study that followed 508 postmenopausal
women receiving testosterone in addition to usual hormone therapy,
evaluated the role of testosterone in hormone replacement therapy.
The observations began in 1987 and ended in 1999. Participants received
testosterone implants 50-150mg, with a common dose of 100mg, every
5 months in addition to estrogen or estrogen and progestin treatment.
The testosterone dose was titrated to relieve symptoms, improve
bone mineral density, and decrease possible adverse effects. Seven
invasive cases of breast cancer were seen throughout the study.
Six out of the seven cases were seen in the estrogen/progestin/testosterone
arm. In contrast, only one case was seen in the estrogen/testosterone
arm of this study.3 In comparison, the incidence of breast
cancer was 2-3 times higher among the estrogen/progestin arm of
The Women’s Health Initiative study (WHI). One might possibly
surmise that the common thread in these results was the progestin
therapy, not the estrogen/testosterone therapy, although this has
not been clinically proven.
It has been shown that estrogen therapy may disrupt the balance
between estrogen and androgens; therefore, lead to estrogenic stimulation
of the breast cells.3 The increased stimulation may lead
to cell proliferation, differentiation and ultimately to breast
cancer. Estrogen therapy has been shown in an animal study to decrease
ovarian production of testosterone by inducing a negative feedback
loop in the ovary where luteinizing hormone levels are decreased,
leading to decreased production of testosterone and ultimately estradiol;
therefore, changing the balance of estrogen and testosterone.5
Experimental data from rodents and monkeys suggest that conventional
estrogen treatment may upset the normal estrogen/androgen balance
and stimulate estrogen in the mammary epithelium.3 Therefore,
increasing a patient’s chance of developing breast cancer.
Clinical studies have provided conflicting results when looking
for a clear correlation between testosterone blood levels and breast
cancer in postmenopausal women.6,8 As of to date, there
aren’t any unbiased trials of sufficient size and duration
to evaluate the effect of testosterone in breast cancer. A review
of published studies did not find an adverse effect from estrogen/testosterone
therapy when evaluating testosterone’s effect on breast cancer.
In addition, one study concluded that testosterone may decrease
the risk of breast cancer when conventional hormone therapy (i.e.
estrogen and progesterone) includes testosterone.3 Another
study looked at androgen receptor antagonist in primates and concluded
that endogenous androgens (such as testosterone) inhibit mammary
proliferation, thus potentially decreasing its impact on breast
There is an abundant amount of information supporting and rejecting
the supplemental use of testosterone in hormone replacement therapy
for postmenopausal women. Theoretically it makes sense that replacing
all hormones that are decreased during menopause, including testosterone,
would have some benefit. Data has suggested that adding testosterone
to conventional hormone therapy in postmenopausal women might reduce
the hormone therapy-induced breast cancer risk in this population.3
Further evaluation is needed to clearly determine the role of testosterone
in postmenopausal women. Testosterone supplementation has not been
conventionally recommended if there’s a family history of
breast cancer, although some physicians believe that there may be
a benefit in maintaining normal levels through supplementation.
In addition, testosterone supplementation is generally warranted
in women complaining of low libido and sexual problems.
For questions and further information, contact Bellevue
- Lillie EO, Bernstein L, Ursin Giske. The Role
of androgens and Polymorphisms in the Androgen Receptor in the
Epidemiology of Breast Cancer. Breast Cancer Res. 2003;5: 164-173.
- The Role of Testosterone Therapy in Postmenopausal
Women: Position Statement of The North Americal Menopause Society.
- Dimitrakakis C, Jones RA, Liu A, Bondy CA. Breast
Cancer Incidence in Postmenopausal Women Using Testosterone in
Addition to Usual Hormone Therapy. Menopause. 2004;11(5):531-535.
- BurgerHG, Hailes J, Nelson J, Menelaus M. Effect
of Combined Implants of Estradiol and Testosterone on Livido in
Postmenopausal Women. BMJ. 1987;294:936-937.
- Leung P CK, Goff AK, Kennedy TG, Armstrong DT.
An Intraovarian Inhibitory Action of Estrogen on Angrogen Production
in vivo. Biology of reproduction. 1978;19: 641-647.
- Missmer SA, Eliassen AH, Barbieri RL, Hankinson
SE. Endogenous Estrogen, Androgen, and Progesterone Concentrations
and Breast Cancer Risk Among Postmenopausal Women. J Natl Cancer
- Cauley JA, Lucas FL Kuller LH, Stone K, Browner
W, Cummings SR. Elevated Serum Estradiol and Testosterone Concentrations
are Associated with a High Risk for Breast Cancer. Ann Intern
- Adly L, Hill D, Sherman ME, Sturgeon SR, Fears
T, Mies C, Ziegler RG, Hoover RN, Schairer C. Serum concentrations
of estrogens, sex hormone-binding globulin, and androgens and
risk of breast cancer in postmenopausal women. Int J Cancer. 2006