Androgen drugs
Androgen drugs are a class of steroid hormones primarily produced by the adrenal glands and reproductive organs, significantly influencing male physical characteristics. The most well-known androgen, testosterone, can be converted to estrogen in the body, a process mediated by the enzyme aromatase. These drugs are utilized in specific cancer treatments, particularly for metastatic hormone-responsive breast cancer in postmenopausal women and prostate cancer. Androgens can be administered orally or through intramuscular injections, with different formulations including testosterone esters and alkylated androgens.
While traditionally not regarded as first-line treatments for breast cancer due to their toxicity and lower response rates, recent research has renewed interest in their application, often in conjunction with aromatase inhibitors. In prostate cancer, androgen therapies work by reducing or blocking androgen levels, thus inhibiting the growth of cancerous cells that rely on these hormones. However, androgen therapy carries potential side effects, particularly for women, which may include masculinizing effects and risks of liver toxicity. Caution is advised in patients with preexisting health conditions, as androgen therapy can exacerbate issues like heart failure and may lead to complications such as hypercalcemia in breast cancer patients.
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Androgen drugs
ATC CODE: G03B
DEFINITION: Androgens are steroid hormones produced by the adrenal glands and testes or ovaries. They are responsible for male sex characteristics in the body. Testosterone, an endogenous androgen, is converted to estrogen by the enzyme aromatase. Androgenic agents can be used in the treatment of prostate and breast cancers.
Cancers treated: Metastatic hormone-responsive breast cancer in postmenopausal women, or in premenopausal women who have undergone ovary ablation; prostate cancer; prostate cancer
Subclasses of this group:Anabolic steroids, alkylated androgens, testosterone esters
Delivery routes: Administered orally as tablets or capsules, or by injection
How these drugs work: Testosterone esters are lipophilic compounds that, when dissolved in oil, are administered via intramuscular injection. Alkylated androgens can be given orally, as their metabolic deactivation is hindered by the alkyl group at the 17α position.
The mechanism of action for androgenic agents in breast cancer blocks the growth of estrogen-dependent tumors by inhibiting aromatase activity. Androgen drugs were not typically considered first-line therapy for breast cancer as they are more toxic than other hormonal agents and the response rates were low. However, emerging research in the 2020s has increased their use. When used, androgens are frequently given in combination with aromatase inhibitors to inhibit the production of estrogen in vivo.
In patients with prostate cancer, androgen therapies reduce or block androgen levels, slowing the progressing of cancerous cells. Because androgen helps prostate cancer cells proliferate, inhibiting their growth by blocking the hormone inhibits cancer cell growth.
Side effects: Androgens are male sex hormones and can cause masculinizing effects in women, including deepening voice, hirsutism, acne, and clitoral enlargement. Alkylated androgens are less potent than testosterone and hence possess a lower risk of these side effects, but liver toxicity, cholestatic hepatitis, and jaundice can occur at relatively low doses. Androgen therapy should be discontinued following abnormal liver function tests until the cause has been determined.
Androgen therapy in patients with preexisting cardiac, renal, or disease increases the risk of edema and progression to congestive heart failure. In such cases, dosing should be discontinued and administration of a diuretic considered.
Breast cancer patients undergoing androgen therapy are at increased risk of bone breakdown and reabsorption, leading to hypercalcemia. If this occurs, then drug therapy should be discontinued, and the patient evaluated, as hypercalcemia may also indicate the progression of bone metastases.
Bibliography
Campagnoli, C., et al. "Postmenopausal Breast Cancer, Androgens, and Aromatase Inhibitors." Breast Cancer Research and Treatment, vol. 139.1, 2013, pp. 1–11.
Chottanapund, Suthat, et al. "Effect of Androgens on Different Breast Cancer Cells Co-cultured with or without Breast Adipose Fibroblasts." Journal of Steroid Biochemistry and Molecular Biology, vol. 138.3, 2013, pp. 54–62.
Dimitrakakis, Constantine, and Carolyn Bondy. “Androgens and the Breast.” Breast Cancer Research: BCR, vol. 11.5, 2009, p. 212. doi:10.1186/bcr2413.
Garay, Joseph P., and Ben H. Park. "Androgen Receptor As a Targeted Therapy for Breast Cancer." American Journal of Cancer Research, vol. 2, no. 4, 2012, pp. 434-445, www.ncbi.nlm.nih.gov/pmc/articles/PMC3410582. Accessed 17 June 2024.
“Hormone Therapy for Prostate Cancer.” American Cancer Society, 22 Nov. 2023, www.cancer.org/cancer/types/prostate-cancer/treating/hormone-therapy.html. Accessed 17 June 2024.
“Hormone Therapy for Prostate Cancer Fact Sheet.” National Cancer Institute, 22 Feb. 2021, www.cancer.gov/types/prostate/prostate-hormone-therapy-fact-sheet. Accessed 17 June 2024.
Kotsopoulos, Joanne, and Steven A. Narod. "Androgens and Breast Cancer." Steroids, vol. 77.1–2, 2012, pp. 1–9.
“Study Reveals New Understanding of How Androgen Therapy Affects Breast Tissue.” Cedars-Sinai, 8 Mar. 2023, www.cedars-sinai.org/newsroom/study-reveals-new-understanding-of-how-androgen-therapy-affects-breast-tissue. Accessed 17 June 2024.