What are androgens and why do they matter in prostate cancer?
Androgens are male sex hormones, and early prostate cancers need them to grow. That single fact is the reason a whole family of prostate cancer treatments exists.
The two main androgens are testosterone and dihydrotestosterone, usually shortened to DHT. They drive the development and upkeep of male characteristics.
Where they come from
The chain starts in the brain. The hypothalamus releases LHRH. That signal tells the pituitary gland to release luteinizing hormone. That hormone reaches the testicles. The testicles make most of the body's testosterone. The adrenal glands, which sit above the kidneys, make most of the rest.
Inside a prostate cell, testosterone binds to a docking point called the androgen receptor. Or it is turned into DHT first. DHT grips that receptor more tightly than testosterone does. So it matters more than its small amount suggests.
Why the cancer depends on them
Prostate cancer cells keep the machinery normal prostate cells use. Androgens promote the growth of both. Early on, cutting off the supply slows the cancer down. Such tumors are called castrate sensitive, androgen dependent, or hormone sensitive.
The dependence does not last forever. Most prostate cancers eventually become castration resistant, meaning they keep growing even when testosterone is very low or undetectable. NCI notes that older names like hormone resistant and androgen independent have fallen out of use. These tumors are not truly independent of androgens after all. The distinction is practical. Newer hormone drugs still work against many castration-resistant cancers.
Three ways treatment goes after them
Current treatments attack the same target from different angles.
Cutting production at the testicles is the most common first step, called androgen deprivation therapy or ADT. Surgery to remove both testicles is called orchiectomy. It drops blood testosterone by 90% to 95%. LHRH agonists such as leuprolide, goserelin, and triptorelin do the same job with drugs. Unlike surgery, that effect reverses when treatment stops. LHRH antagonists such as degarelix and relugolix skip the testosterone flare. That flare is a brief rise in testosterone that LHRH agonists cause at the first dose.
Blocking the receptor is the second angle. Androgen receptor blockers such as bicalutamide, enzalutamide, apalutamide, and darolutamide compete with androgens for that docking point.
Shutting down production body-wide is the third. Abiraterone blocks an enzyme called CYP17. The testicles, adrenal glands, and prostate tumor tissue all need it to make testosterone. NCI says this class lowers testosterone further than any other known treatment.
What low androgens cost
Androgens act on far more than the prostate. Removing them has wide effects. These include loss of sex drive, erectile problems, hot flashes, bone thinning and fractures, muscle loss, and weight gain. They also include changes in blood fats, insulin resistance, mood swings, fatigue, and breast tissue growth.
Two of these are worth planning for. Bone loss can be treated with zoledronic acid, alendronate, or denosumab. Those drugs carry a rare but serious risk of osteonecrosis of the jaw. Exercise may reduce bone loss, muscle loss, weight gain, fatigue, and insulin resistance. Trials are testing how far that goes.
Get emergency care the same day for new back pain with leg weakness, numbness, or loss of bladder or bowel control. Prostate cancer spreads to bone. Pressure on the spinal cord is treated in hours, not days. Our guide to hormone therapy for prostate cancer covers the drug groups, and the overview of prostate cancer explains staging and treatment choices.
Sources
Want the full picture? Read our complete explanation: Hormone Therapy for Prostate Cancer
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