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Phase II Study of Testosterone Replacement in Women Experiencing Aromatase Inhibitor Side-Effects in Adjuvant Therapy for Breast Cancer

Phase 2
18 Years
85 Years
Open (Enrolling)
Breast Cancer, Arthralgia, Osteoporosis

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Trial Information

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.

Inclusion Criteria:

- Provision of written informed consent

- Undergone a total mastectomy, a lumpectomy or a quadrantectomy for primary breast
cancer +/-chemo, +/-radiotherapy

- Have commenced anastrozole therapy within the previous 6 months

- Presence of node negative or positive disease

- Receptor-positive tumors, defined as ER ≥10% of the tumor cells positive by
immunocytochemical evaluation

- Postmenopausal whether induced by surgery, radiotherapy (chemotherapy-induced
amenorrhea may be difficult to determine they may be amenorrhoeic but still have
functioning ovaries), or by being naturally amenorrhoeic, for 1 year or more if
younger than 50 and for 6 months if 50 or older

- Postmenopausal levels of FSH/LH/E2 (follicle stimulating hormone, luteinizing
hormone, oestrogen) according to the definition of "postmenopausal range" for the
laboratory involved

- Have developed arthralgia and associated joint symptoms whilst being treated with
anastrozole with a score of 40mm or greater on a pain and stiffness 100mm VAS

- WBC ≥ 3.0 x 109/L, granulocytes ≥ 1.5 X 109/L and platelets ≥ 100 x 109/L.

- AST/SGOT or ALT/SGPT ≤ 3 times ULN Serum creatinine ≤ 2 times ULN

Exclusion Criteria:

- Presence of metastatic disease

- Diabetes mellitus or glucose intolerance defined as a fasting glucose >6mmol/l

- Previous or concomitant other (non-breast cancer) malignancy within the previous 5

- Presence of other non-malignant systemic diseases which may prevent prolonged

- History of coronary artery disease or no history of previous coronary heart disease
but at least two other coronary heart disease risk factors: LDL ≥8.8 mg/dL OR if
fewer than two other coronary heart disease risk factors: LDL ≥10.45 mg/dL or total
fasting cholesterol ≥ 13.2 mg/dL

- Patients on hormone replacement therapy (HRT) within 4 weeks before trial treatment
was initiated

- Patients on breast cancer chemoprevention with anti-oestrogens if less than 18 months
between stopping and diagnosis of breast cancer

- Are at risk of transmitting Human Immunodeficiency Virus or viral hepatitis via
infected blood

- Known hypersensitivity to any component of testosterone

- Unable to comply with study requirements

- Taking the following concomitant medications at the screening visit-bisphosphonate,
anti-cancer treatment other than anastrozole (this includes Herceptin).

- Prolonged systemic corticosteroid treatment, except for topical applications (e.g.
for rash), inhaled sprays (e.g. for obstructive airways diseases), eye drops or local
injections (e.g. intra-articular). Note: Short duration (< 2 weeks) of systemic
corticosteroids is allowed (e.g. for Chronic Obstructive Pulmonary Disease) but not
within 1 month prior to randomisation.

- Any investigational drugs

- Systemic hormone replacement therapy

- Pregnant or lactating women

- Patients with history of fragility fracture or low BMD, osteoporosis or osteopenia

- Known liver disease

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Outcome Measure:

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.

Outcome Time Frame:

3 months

Safety Issue:


Principal Investigator

Stephen N Birrell, MD PhD

Investigator Role:

Study Director

Investigator Affiliation:

Chavah Pty Ltd


Australia: Department of Health and Ageing Therapeutic Goods Administration

Study ID:




Start Date:

July 2007

Completion Date:

June 2009

Related Keywords:

  • Breast Cancer
  • Arthralgia
  • Osteoporosis
  • breast
  • neoplasms
  • anastrazole
  • testosterone
  • Arthralgia
  • Breast Neoplasms
  • Osteoporosis