Testosterone Suppression (ADT) & Fatigue Management

NCI explains that in prostate cancer, "male sex hormones can cause prostate cancer to grow," so "drugs, surgery, or other hormones are used to reduce the amount of male hormones or block them from working. This is called androgen deprivation therapy (ADT)."

Lowering testosterone on purpose works against the cancer. It also removes a hormone your body has used for decades, and you feel that everywhere.

NCI describes three main forms of ADT: orchiectomy, "a surgical procedure to remove both testicles"; LHRH agonists, "which prevent the pituitary gland from secreting a hormone called luteinizing hormone"; and LHRH antagonists, which "prevent LHRH from binding to its receptors in the pituitary gland." Antiandrogens and androgen synthesis inhibitors such as abiraterone block the hormone's effect rather than its production.

For ADT, the full list is: "loss of interest in sex (lowered libido), erectile dysfunction, hot flashes, loss of bone density, bone fractures, loss of muscle mass and physical strength, changes in blood lipids, insulin resistance, weight gain, mood swings, fatigue, growth of breast tissue (gynecomastia)."

Antiandrogens add "diarrhea, breast tenderness, nausea." NCI notes that "flutamide may damage the liver, and enzalutamide and apalutamide may cause fractures." Androgen synthesis inhibitors can cause "diarrhea, itching and rashes, fatigue, erectile dysfunction (with long-term use), and, potentially, liver damage."

NCI's summary on hot flashes says that surgery to remove one or both testicles "can trigger a set of symptoms that include hot flashes and night sweats," and that "hormone therapy with gonadotropin-releasing hormone or estrogen also causes these symptoms in men." Treatment "may include estrogens, progestin, antidepressants, and anticonvulsants" — worth knowing, because men are sometimes told nothing can be done. See hot flashes during cancer treatment.

Loss of muscle mass and physical strength, weight gain, changes in blood lipids, and insulin resistance all appear on NCI's list. These arrive gradually, which is why men often notice the shape of their body has changed before they notice the strength has.

NCI gives one countermeasure: "Exercise may help reduce some of the side effects of hormone therapy, including bone loss, muscle loss, weight gain, fatigue, and insulin resistance." That is one recommendation covering five problems on this page. See exercise during cancer treatment.

Bone loss is the effect that outlasts the treatment. NCI's prostate treatment summary states that "men who are treated with antiandrogen therapy or orchiectomy are at an increased risk of bone loss. In these men, bisphosphonate drugs lessen the risk of bone fracture."

The fact sheet names zoledronic acid (Zometa) and alendronate (Fosamax), which "can be used to increase bone mineral density in men who are undergoing hormone therapy, as can a newer drug, denosumab (Prolia)." It also flags the trade-off: these "are associated with a rare but serious side effect called osteonecrosis of the jaw." The American Cancer Society says bone density is measured with a DEXA scan, which "you may have before, during, and after cancer treatment." More at bone loss after hormone therapy.

Fatigue is on NCI's list for both ADT and androgen synthesis inhibitors, and exercise is the intervention NCI names for it. See fatigue during cancer treatment.

On mood, the fact sheet lists only "mood swings." NCI's depression summary separately includes androgen deprivation therapy among the treatments associated with depressive symptoms. That is thinner evidence than the bone or metabolic material, but enough to raise low mood with your team rather than filing it under getting older.

Lowered libido, erectile dysfunction, and gynecomastia are all listed. One practical point from NCI: erectile dysfunction drugs "do not usually work for men undergoing hormone therapy because these drugs do not address the loss of libido (sexual desire) that is associated with a lack of androgens." Our page on erectile dysfunction after prostate cancer treatment covers the options in full.

NCI is careful here: "Most of the sexual and emotional side effects caused by low levels of androgens will eventually go away if a man stops taking hormone therapy. However, particularly for older men and those who received ADT for a long time, testosterone levels may not fully recover and these side effects may not disappear completely. Some physical changes that have developed over time, such as bone loss, will remain after stopping hormone therapy."

Some men are offered intermittent ADT, given "in cycles with breaks between drug administrations rather than continuously." NCI says a potential benefit is that "the temporary break from the side effects of hormone therapy may improve a man's quality of life," but also states plainly: "No trials have compared intermittent ADT with continuous ADT."

Erectile Dysfunction After Prostate Cancer Treatment, Bone Loss After Hormone Therapy, Hot Flashes During Cancer Treatment, and Fatigue During Cancer Treatment.

• National Cancer Institute: Hormone Therapy for Prostate Cancer Fact Sheet. https://www.cancer.gov/types/prostate/prostate-hormone-therapy-fact-sheet
• National Cancer Institute: Prostate Cancer Treatment (PDQ) — Patient Version. https://www.cancer.gov/types/prostate/patient/prostate-treatment-pdq
• National Cancer Institute: Hot Flashes and Night Sweats (PDQ) — Patient Version. https://www.cancer.gov/about-cancer/treatment/side-effects/hot-flashes-pdq
• National Cancer Institute: Depression (PDQ) — Health Professional Version. https://www.cancer.gov/about-cancer/coping/feelings/depression-hp-pdq
• American Cancer Society: Osteoporosis. https://www.cancer.org/cancer/side-effects/osteoporosis.html