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, 9 (4), 163-80

Estrogenic Side Effects of Androgen Deprivation Therapy

Estrogenic Side Effects of Androgen Deprivation Therapy

Theresa A Guise et al. Rev Urol.

Abstract

Androgen deprivation therapy (ADT) is part of standard therapy for locally advanced or metastatic prostate cancer and is frequently used in men with a rising prostate-specific antigen following radical prostatectomy or radiation therapy. In some men, ADT may be administered for years or even decades. The intended therapeutic effect of ADT is testosterone deficiency. Because estrogen is a normal metabolite of testosterone, ADT also results in estrogen deficiency. ADT has a variety of adverse effects, many of which are primarily related to estrogen deficiency. Bone mineral density may decrease by 4% to 13% per year in men receiving ADT. The fracture rate for patients on ADT averages 5% to 8% per year of therapy. Hot flashes, gynecomastia, and breast tenderness are common side effects associated with ADT. In the clinic, minimum baseline testing should include weight measurement, blood pressure reading, and fasting lipid panel and serum glucose tests. Currently, there are no large outcome trials in men on ADT testing the available therapies for adverse effects. No therapies are specifically approved for treatment of adverse effects in men on ADT. Although some therapies can be used for a single indication (based upon small studies), there is currently no agent to treat the multiple estrogenic side effects of ADT.

Keywords: Androgen deprivation therapy; Cardiovascular disease; Gynecomastia; Male hot flashes; Osteoporosis fracture.

Figures

Figure 1
Figure 1
Prevalence of Osteoporosis and Low Bone Mass in Men Aged 50 and Over. Adapted with permission from America’s Bone Health: The State of Osteoporosis and Low Bone Mass in Our Nation, page 5, 2002, National Osteoporosis Foundation, Washington, DC 20037.
Figure 2
Figure 2
Fracture risk as a function of age and gender. Reprinted with permission from Cooper C and Melton LJ III.
Figure 3
Figure 3
Clinical algorithm for assessment and treatment of ADT-associated bone loss in men with prostate cancer. BMD, bone mineral density; DXA, dual-energy x-ray absorptiometry; RANKL, receptor activator of the nuclear factor kappa β ligand; SERMs, selective estrogen receptor modulators; CT, computed tomography. Reprinted with permission from Diamond TH et al.
Figure 4
Figure 4
Zoledronic acid increases bone mineral density in patients with nonmetastatic and metastatic prostate cancer on ADT. *Statistically significant difference for zoledronic acid compared with placebo (P < .001). Reprinted with permission from Smith MR et al. Copyright © Elsevier 2003.
Figure 5
Figure 5
Toremifene 80 mg increased BMD in prostate cancer patients treated with androgen deprivation therapy. Interim analysis of first 197 patients. BMD, bone mineral density; DXA, dual-energy x-ray absorptiometry. Adapted with permission from Smith MR et al.

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