Phase II Study of Testosterone Replacement in Women Experiencing Aromatase Inhibitor Side-Effects in Adjuvant Therapy for Breast Cancer
Anastrozole (Arimidex®) is a selective aromatase inhibitor (a drug that interferes with the
making of oestrogens). Reduction in serum oestrogen levels in a hormone-receptor positive
breast cancer patient is clearly beneficial in delaying the regrowth of breast cancer cells
in the body. Anastrozole is effective in reducing serum oestrogen levels which results in
several significant side-effects with 2 being of significant importance; joint pain and
stiffness and bone thinning or osteoporosis. The question being asked in this trial is if
replacement of testosterone to women receiving Anastrozole can have a reduction in these 2
common side-effects. Women normally have circulating in their blood 3 major sex hormones:
oestrogen, testosterone and progesterone. Each of these is produced by the ovaries.
Oestrogen is also made throughout the body but particularly in body fat. Testosterone can
also be made in other parts of the body from hormones (DHEA and DHEAS) that are produced by
the adrenal glands. At the time of natural menopause, surgical removal of the ovaries or
destruction of the ovaries by chemotherapy, oestrogen and progesterone levels fall
precipitously. Testosterone levels however fall more gradually with increasing age such that
a woman in her forties has on average only half of the testosterone circulating in her
bloodstream as does a woman in her twenties. After a woman has her ovaries removed by
surgery or destroyed by chemotherapy testosterone levels can fall by up to fifty percent.
However testosterone does not change across menopause, although this varies somewhat between
women. Testosterone is known to have many physiological roles in women. Firstly, oestrogen
is actually made from testosterone, and without the ability of our bodies to make
testosterone we cannot make oestrogen. Testosterone appears to have direct independent
effects in different parts of the body, and some women may experience a variety of physical
symptoms when their blood levels fall. Anastrazole almost completely blocks the formation of
oestrogen from testosterone. Thus the question being asked in this trial is, can increasing
the blood level of testosterone reduce specific side-effects caused by reduction
availability of hormones in joints and bones.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
Reduces arthralgia and associated joint symptoms as indicated by the change in hand or large joint pain from baseline to 3 months using a 100mm visual analogue scale for pain.
Stephen N Birrell, MD PhD
Chavah Pty Ltd
Australia: Department of Health and Ageing Therapeutic Goods Administration