Hormone therapy for prostate cancer is a treatment that starves cancer cells of testosterone, the fuel they need to grow. It works because prostate cancer cells depend on male hormones (androgens) to survive and multiply. By cutting off or blocking testosterone, hormone therapy slows tumor growth, shrinks existing cancer, and lowers PSA levels. It is one of the most widely used treatments for prostate cancer, particularly for cancer that has spread beyond the prostate or returned after surgery or radiation.
How Testosterone Drives Prostate Cancer
Testosterone and other androgens promote the growth of both normal and cancerous prostate cells. They do this by binding to androgen receptors, proteins sitting on and inside prostate cells. Once testosterone locks onto these receptors, it switches on genes that tell the cell to grow and divide. In healthy tissue, this is part of normal function. In cancerous tissue, it accelerates tumor growth.
Hormone therapy targets this process in one of three ways: reducing the amount of testosterone the body makes, blocking testosterone from reaching cancer cells, or both. The goal is to bring testosterone down to extremely low levels, typically below 50 ng/dL (the threshold used by the American Urological Association) and ideally below 20 ng/dL, which mirrors levels seen after surgical removal of the testicles. European guidelines have noted that getting below 20 ng/dL is associated with better outcomes than staying in the 20 to 50 range.
Types of Hormone Therapy
Injections That Suppress Testosterone Production
The most common first-line approach is androgen deprivation therapy, or ADT, which reduces testosterone production by the testicles. This usually involves injections given monthly or every few months. These drugs act on the pituitary gland, the small structure at the base of the brain that signals the testicles to make testosterone.
There are two categories of injectable ADT, and they work differently. The first type (called agonists) initially overstimulates the pituitary gland, causing a brief surge in testosterone that lasts about a week before the system shuts down and testosterone plummets. This initial spike, known as a “flare,” can temporarily worsen symptoms, so doctors often prescribe a short course of a blocking medication alongside it. The second type (called antagonists) skips this flare entirely by directly blocking the pituitary’s hormone receptors, producing a rapid drop in testosterone without the initial surge.
A Daily Pill Option
A newer oral medication called relugolix offers an alternative to injections. It works as an antagonist, directly blocking receptors on the pituitary gland to rapidly suppress testosterone. In clinical trials, about 97% of men taking relugolix maintained very low testosterone levels through 48 weeks, compared with 89% of men receiving a standard injection.
The pill also showed notable advantages for heart health. Men receiving the injection experienced major cardiovascular events (nonfatal heart attack or stroke) at roughly twice the rate of those on the pill: 6.2% versus 2.9%. For men who already had a history of heart problems, that gap widened dramatically, with 17.8% of the injection group experiencing cardiac events compared to 3.6% on the pill. Another practical benefit: testosterone levels returned to normal within a few months of stopping the oral medication, which can matter for men on intermittent therapy.
Androgen Receptor Blockers
These medications don’t lower testosterone levels. Instead, they compete with testosterone for access to androgen receptors on cancer cells. By occupying the receptor first, they prevent testosterone from activating the growth signals. These are often used in combination with ADT for a more complete hormonal blockade.
Androgen Synthesis Inhibitors
Standard ADT only shuts down testosterone from the testicles. But small amounts of androgens are also produced by the adrenal glands (which sit on top of the kidneys) and even by prostate cancer cells themselves. Androgen synthesis inhibitors block production from all three sources, making them useful when cancer continues to progress despite standard ADT.
Surgical Option
Removal of the testicles (orchiectomy) is the oldest form of hormone therapy and permanently eliminates the body’s main testosterone source. It achieves castrate levels immediately and requires no ongoing medication. However, it is irreversible, and most men today prefer drug-based options that can be stopped or adjusted.
When Hormone Therapy Is Used
Hormone therapy plays different roles depending on how advanced the cancer is. For cancer that has spread to lymph nodes, bones, or other organs, it is often the backbone of treatment, sometimes used for years. For locally advanced cancer that hasn’t spread far, it is frequently combined with radiation therapy to improve the odds of a cure. In this setting, it may be given for several months before radiation (to shrink the tumor), during radiation, and for a period afterward.
It can also be used when PSA levels rise after surgery or radiation, signaling that cancer cells are still active somewhere in the body. Some men receive it intermittently, cycling on and off treatment to reduce side effects while still controlling the cancer. Others stay on it continuously. The approach depends on how aggressive the cancer is and how the body responds.
What Happens to PSA During Treatment
PSA (prostate-specific antigen) is a protein produced by prostate cells, and its blood level is the primary way doctors track how well treatment is working. When hormone therapy is effective, PSA levels drop, sometimes to undetectable levels. This decline typically happens within the first few months. Doctors monitor PSA regularly throughout treatment, and a rising PSA is often the first sign that the cancer is finding ways to grow despite low testosterone.
Side Effects of Living With Low Testosterone
Because testosterone affects far more than the prostate, suppressing it has wide-ranging effects on the body. The most common side effects include hot flashes, loss of sex drive, erectile dysfunction, fatigue, and loss of muscle mass. Many men gain weight, particularly around the midsection, and develop features of metabolic syndrome: higher blood sugar, rising cholesterol, and increased insulin resistance. A meta-analysis found that men on ADT had a 75% higher risk of developing metabolic syndrome compared to men not on the therapy.
Bone loss is a serious long-term concern. Testosterone helps maintain bone density, and without it, bones thin more quickly, raising the risk of fractures. Research shows that bone-protective medications can significantly counteract this. In a meta-analysis, men who took bisphosphonates (a class of bone-strengthening drugs) during ADT saw their lumbar spine bone density improve by about 7% compared to those who didn’t, with smaller but meaningful gains at the hip and femoral neck. Weight-bearing exercise and adequate calcium and vitamin D intake are also recommended, though there is no consensus on a single best prevention strategy.
Emotional and cognitive changes are common too. Some men report difficulty with memory and concentration, mood swings, or depression. Breast tissue can enlarge and become tender. These effects tend to improve if therapy is stopped, but for men on long-term or permanent ADT, they become a persistent quality-of-life issue that needs active management.
Heart Health and Hormone Therapy
The relationship between ADT and cardiovascular risk has been studied extensively. Observational data consistently links standard injectable ADT (particularly the agonist type) with increased risks of heart disease, heart attack, and stroke. One large meta-analysis found that men on these injections had a 36% higher risk of cardiovascular death, a 20% higher risk of heart attack, and a 19% higher risk of nonfatal cardiovascular disease compared to men not on hormone therapy.
Antagonist-type medications appear safer for the heart. Pooled data showed a 56% lower risk of heart attack with antagonists compared to agonists. This is one reason the oral pill relugolix, an antagonist, has generated considerable interest. For men with pre-existing heart conditions, the choice of hormone therapy type can meaningfully affect cardiovascular outcomes.
When the Cancer Stops Responding
Hormone therapy controls prostate cancer effectively for months or years, but in many cases the cancer eventually adapts. This stage is called castration-resistant prostate cancer. The cancer continues to grow even though testosterone levels remain very low.
Cancer cells develop several escape routes. The most common is overproduction of androgen receptors, allowing the cell to capture and respond to the tiny amounts of testosterone still circulating. In 10 to 20% of castration-resistant cases, the androgen receptor itself mutates, becoming less selective. These mutated receptors can be activated by other hormones like progesterone or estrogen, or even by the very drugs designed to block them. Some cancer cells also ramp up their own internal production of androgens, creating a self-sustaining fuel supply despite system-wide suppression.
When standard hormone therapy stops working, treatment typically shifts to more potent hormone-blocking agents (like androgen synthesis inhibitors or newer receptor blockers), chemotherapy, or other approaches. Even at this stage, most men remain on some form of testosterone suppression because allowing levels to rise would accelerate growth further.