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. You feel that everywhere.

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

For ADT, NCI lists these side effects.

• Loss of interest in sex (lowered libido).
• Erectile dysfunction.
• Hot flashes.
• Loss of bone density, and 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 also notes two drug-specific risks. It says that "flutamide may damage the liver." And that "enzalutamide and apalutamide may cause fractures." Androgen synthesis inhibitors have their own list. They can cause "diarrhea, itching and rashes, fatigue, erectile dysfunction (with long-term use), and, potentially, liver damage."

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

Several of these appear on NCI's list. Loss of muscle mass and physical strength. Weight gain. Changes in blood lipids. Insulin resistance. They arrive gradually. That is why men often notice the shape of their body has changed before they notice the strength has.

NCI gives one countermeasure. It is exercise. "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). These "can be used to increase bone mineral density in men who are undergoing hormone therapy, as can a newer drug, denosumab (Prolia)." NCI also flags the trade-off. These drugs "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. Exercise is the one thing NCI names for it. See fatigue during cancer treatment.

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

Lowered libido, erectile dysfunction, and gynecomastia are all listed. NCI makes one practical point about the pills. Erectile dysfunction drugs "do not usually work for men undergoing hormone therapy." The reason is that 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. This is what it says. "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. It is given "in cycles with breaks between drug administrations rather than continuously." NCI names a possible benefit. "The temporary break from the side effects of hormone therapy may improve a man's quality of life." But NCI also states plainly: "No trials have compared intermittent ADT with continuous ADT."

• Call 911 or go to an emergency department if a small knock, twist or stumble leaves you unable to bear weight on a leg or with sudden severe pain in the back or hip. Bone thins on hormone therapy, and NCI notes that enzalutamide and apalutamide may cause fractures, so a break can follow a force that would once have meant nothing.
• Call your care team the same day if you are taking flutamide and notice yellowing of the skin or eyes, dark urine, pain in the upper right part of the stomach, extreme tiredness, or flu-like aching. MedlinePlus warns that flutamide may cause liver damage that can be serious or life-threatening.
• Call your care team within a day or two if hot flashes are wrecking your sleep, mood has stayed flat or hopeless for a couple of weeks, or breast tissue becomes tender or swollen. None of these are things to absorb quietly; each has an option attached.

More on this site. Erectile Dysfunction After Prostate Cancer Treatment. Bone Loss After Hormone Therapy. Hot Flashes During Cancer Treatment. 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
• MedlinePlus, U.S. National Library of Medicine: Flutamide. https://medlineplus.gov/druginfo/meds/a697045.html
• American Cancer Society: Osteoporosis. https://www.cancer.org/cancer/side-effects/osteoporosis.html