Second-Line Hormone Therapy for Prostate Cancer (2025)

What is Second-Line Hormone Therapy?
Second-line hormone therapy refers to treatments used when the first-line hormone therapy for prostate cancer is no longer working. Prostate cancer cells usually need male hormones (like testosterone) to grow​ cancer.gov. Initial hormone treatments (such as surgery or injections to lower testosterone) can slow the cancer, but over time the cancer can adapt and start growing again even with low testosterone. This stage is often called castration-resistant prostate cancer. When this happens, doctors turn to second-line hormone therapies – new medicines that can further target the cancer’s growth​ medlineplus.gov. All the therapies discussed here are FDA-approved for prostate cancer as of 2025, meaning they have been tested and approved for use in patients. These treatments are used to control the cancer and help patients live longer when standard hormone therapy alone is not enough​ pmc.ncbi.nlm.nih.gov.

How Do These Therapies Work?
Prostate cancer is driven by male hormones (also called androgens, like testosterone) which act as “fuel” for the cancer​ cancerresearchuk.org. Second-line hormone therapies work by cutting off the cancer’s fuel or blocking its effects. In simple terms, they either lower the amount of testosterone in the body even more or block the cancer from using any testosterone that remains. By doing so, these treatments can slow down or shrink the cancer, even after the initial hormone therapy has stopped helping​.

• Medicines that Block Hormone Signals (Anti-Androgens): Several newer drugs can block the effect of testosterone on prostate cancer cells. These medicines act like a shield, so even if small amounts of hormone are still in the body, the cancer cells cannot “see” or use it​. This stops the hormones from telling the cancer to grow​. These drugs are usually pills taken once a day at home. Examples of FDA-approved anti-androgens include enzalutamide (brand name Xtandi), apalutamide (Erleada), and darolutamide (Nubeqa). (Older anti-androgens like bicalutamide, flutamide, and nilutamide also block testosterone, but the newer drugs tend to be more effective for advanced cancer​.) Enzalutamide, apalutamide, and darolutamide are often called androgen receptor inhibitors, because they attach to the prostate cancer cells’ androgen receptor (the “lock” for the testosterone “key”) and prevent it from being activated​. In simple terms, they keep the cancer cells from using testosterone, which slows the growth and spread of the cancer cells​. Patients on these medications will continue their original hormone therapy (e.g. injections) to keep testosterone levels low, while the pills block any remaining hormone activity​.

• Medicine that Lowers Hormone Levels Further (Androgen Synthesis Inhibitor): The main drug in this category is abiraterone acetate (brand name Zytiga). Abiraterone is a pill that stops the body from making testosterone and other androgens​. Even after the testicles are not making testosterone (from first-line therapy), the body can still produce small amounts of these hormones from the adrenal glands or even from the tumor itself​. Abiraterone blocks an enzyme needed to produce androgens, greatly reducing the hormone levels in the whole body. This essentially starves the cancer of any remaining fuel. Abiraterone is taken along with a steroid pill (prednisone) to help the body tolerate the treatment and reduce certain side effects​. It has been shown to help men whose cancer “has not gotten better with other hormone therapy,” meaning the cancer became resistant to initial treatments​. By using abiraterone, doctors can further lower hormone levels and slow the cancer’s growth when other hormone treatments are no longer effective​.

What to Expect from Treatment:
Second-line hormone therapies are usually given as daily oral medications (pills), often alongside the ongoing injections or implants that were part of the first-line hormone therapy​. Your doctor will explain how and when to take these medicines. For example, enzalutamide, apalutamide, and darolutamide are taken by mouth once daily (the pills are swallowed whole)​. Abiraterone is also a daily pill but is typically taken on an empty stomach and must be combined with prednisone (a steroid) as part of the regimen​. It’s important to follow your doctor’s instructions on how to take these medicines exactly, because taking them the right way helps them work best. These therapies do not cure prostate cancer, but they can hold the cancer in check for a significant time, improve symptoms, and help men live longer with advanced disease​. Your medical team will keep track of your progress with regular check-ups. They will likely do blood tests for PSA(prostate-specific antigen, a protein that reflects prostate cancer activity) to see if the treatment is working​. Typically, if the treatment is effective, PSA levels will stay low; if PSA starts rising, it may indicate the cancer is becoming active again​. The doctor may also use imaging tests (like bone scans or CT scans) from time to time to monitor the cancer. It’s not possible to predict exactly how long each therapy will work for a given person​, but these second-line treatments have given patients more options to control the cancer after initial therapies.

Possible Side Effects
Because second-line hormone therapies further lower or block male hormones, many side effects are similar to those of first-line hormone therapy (androgen deprivation). Testosterone affects many parts of the body, so reducing or blocking it can cause various changes​. Side effects include:

• Reduced sexual desire and function: It’s common to experience a lower libido (sex drive) and erectile dysfunction (trouble getting or keeping an erection)​. These occur because testosterone is important for sexual function.
• Hot flashes: Many men have hot flashes, which are sudden feelings of warmth or sweating​. These can be similar to the hot flashes women have in menopause. They may happen at any time and can be uncomfortable, but there are ways to manage them if they are troublesome (discuss with your doctor).
• Fatigue and mood changes: Hormone therapy can make you feel very tired or lacking energy. You might also experience mood swings, such as feeling more emotional, sad, or irritable than usual​. This is because hormones can affect your mood and energy levels. Getting regular light exercise, when possible, and staying engaged in enjoyable activities can help combat fatigue and low mood – but always balance activity with rest as needed.
• Bone and muscle effects: Over time, low hormone levels can lead to loss of bone density (weaker bones)​and muscle mass loss​. This means bones might become more fragile (increasing the risk of fractures) and muscles may become smaller or weaker. Your doctor might check your bone health and can recommend calcium or vitamin D supplements, or even other medications, to protect your bones if needed. Strength exercises (with your doctor’s approval) might help maintain muscle and bone strength.
• Weight gain and metabolic changes: Some men gain weight (especially around the belly) or notice changes in body fat distribution. There can also be changes in cholesterol or blood sugar levels​. Your healthcare team may monitor these through blood tests. Eating a healthy diet and staying physically active can mitigate some of these effects, but always consult your doctor or a nutritionist for guidance.

Each specific drug can have additional side effects. For example, enzalutamide can sometimes cause dizziness, or, rarely, seizures (so your doctor will ask about any history of seizures). Apalutamide may cause skin rashes in some patients. Darolutamide might cause fatigue but is noted to possibly have fewer mental side effects (because it enters the brain less than some others). Abiraterone can raise blood pressure or cause fluid retention (swelling) and affect liver function, which is one reason it’s given with prednisone – the steroid helps prevent some of these issues. You will have regular blood tests (for example, to check liver enzymes and potassium levels) if you are on abiraterone​. It’s important to tell your doctor about any side effects you experience. Many side effects can be managed. Doctors can prescribe treatments for hot flashes, erectile dysfunction, or fatigue, and they can adjust doses or give breaks if side effects are severe​. Do not stop taking your hormone therapy on your own – always discuss with your medical team, since suddenly stopping some of these medications (like abiraterone or prednisone) can be harmful​. With good communication, your doctor can help you feel as comfortable as possible while on therapy.

Practical Tips for Working With Your Doctor
Working closely with your healthcare team will help you get the most benefit from second-line hormone therapy. Here are some practical tips:

• Take Medications Exactly as Prescribed: These therapies work best when taken exactly as directed. Try to take your pills at the same time each day as instructed​. Do not skip doses or stop the medication without consulting your doctor, even if you feel well​. Stopping suddenly can cause your hormone levels to rebound and may allow the cancer to grow faster. If you ever miss a dose or have trouble remembering your medication, let your doctor or nurse know; they can give you strategies to stay on track.
• Continue Your Original Hormone Therapy: In most cases, you will continue your first-line hormone treatments (like LHRH injections or implants) while on the new therapy​. The injection keeps your testosterone level very low, and the new drug adds another layer of protection​. Be sure to keep up with your injection appointments or patch schedules as directed. If you’ve had surgery to remove your testicles (orchiectomy) instead of injections, that effect is permanent – the new medications will work on top of that. Always confirm with your doctor which treatments you should continue; don’t assume you should stop the shots just because you started a pill​
• Attend All Follow-Up Appointments and Tests: Your doctor will schedule regular visits to monitor how you are doing. Make sure to attend all appointments and have all recommended blood tests and scans. Typically, you will get PSA blood tests every few months to check if the treatment is keeping the cancer under control​. The doctor might also check your liver function (especially with abiraterone) and other health markers. These tests are important to catch any changes early. Keeping up with them helps your doctor make timely decisions, like switching therapies if needed. Consider keeping a calendar or setting reminders for appointments and lab tests.
• Report Side Effects and Symptoms: Always tell your doctor about any new symptoms or side effects you experience, even if they seem minor. There is no need to “tough it out” in silence. For example, if you feel extremely tired, depressed, have significant hot flashes, or any unusual symptoms, inform your healthcare team. They may adjust your treatment or provide remedies. Doctors often can prescribe medicines or recommend lifestyle changes to help with side effects (for instance, treatments for hot flashes or physical therapy for muscle weakness)​. By sharing what you feel, you allow your doctor to help you feel better and ensure you stay on therapy safely. Keep a notebook or log of how you feel each day – this can help you remember what to mention during appointments.
• Stay Informed and Involved: Don’t hesitate to ask questions if something is unclear. It’s your right and even responsibility to understand your treatment. If your doctor uses a term you don’t know, feel free to ask what it means. Sometimes bringing a family member or friend to appointments can help – they might catch information you miss and support you in remembering instructions. Being actively involved in your care (by understanding the plan and speaking up about your needs) will help you and your doctor work together as a team.
• Lifestyle and Support: Taking care of your overall health can make a difference during treatment. Ask your doctor if there are safe exercises you can do to maintain strength and bone health (even walking or light weight-bearing exercises can help, if you’re able). Eating a balanced diet with enough calcium and vitamin D is important for your bones; your doctor or a dietitian can guide you on this. Also, consider joining a support group for prostate cancer patients or talking to a counselor if you feel anxious or down. Although not a direct part of hormone therapy, emotional and social support is an important part of coping with cancer treatment. Your healthcare team may help connect you with resources if you ask. Remember, you are not alone—many patients and families are going through similar experiences, and there are communities and professionals ready to help.

Questions to Ask Your Doctor
It’s helpful to come to your appointments with a list of questions. Here are some questions you might want to ask your doctor about second-line hormone therapy:

• Why are you recommending this second-line hormone therapy for me? (Ask your doctor to explain how this treatment will help in your specific case and why it’s the best next step.)
• How does this treatment work to fight my cancer? (Have the doctor explain in simple terms what the drug does inside your body. This can help you understand the purpose of taking it.)
• What are the potential side effects, and how can we manage them? (Make sure you know what to watch for. For example, ask: “What side effects should I tell you about right away?” and “Are there medicines or strategies to help if I get those side effects?”)
• Will I continue my other prostate cancer treatments while on this therapy? (For instance, ask if you should keep getting your hormone shots or other medications. This avoids any confusion about stopping or continuing existing treatments.)
• How long will I need to be on this therapy? (While it’s hard to predict, your doctor can give an idea of how long people typically stay on the treatment and what factors determine that. They can also tell you what might happen if the treatment stops working in the future.)
• How will we know if the treatment is working? (Ask about what improvements or changes in tests you will be looking for – e.g., “Will my PSA go down?” and “How often will we check it?” Also, “Will we do scans regularly?”)
• What should I do to take care of myself while on this therapy? (This invites advice on diet, exercise, bone health, and managing fatigue. Your doctor might have specific recommendations, such as calcium supplements or seeing a nutritionist or physical therapist.)
• Can I continue my normal daily activities on this treatment? (Ask about any activity restrictions. For example, is it okay to continue working, driving, or exercising? Most people can do many normal activities, but it’s good to know if there are any precautions, like being careful to avoid falls if you feel weak, etc.)
• Are there any other treatment options if this therapy doesn’t work for me? (This helps you understand the overall plan. Your doctor can talk about what comes next, such as chemotherapy, other medicines, or clinical trials, if needed in the future. Even though it may be early, knowing the next steps can give you a sense of control and preparedness.)
• What support services are available to me? (You can ask about patient support groups, counseling, or nutritional advice. Sometimes hospitals have classes or resources for managing side effects or connecting with other patients. Your doctor or nurse might direct you to these.)

Feel free to ask any other questions that are on your mind. No question is too small when it comes to understanding your health and treatment. The goal of your healthcare team is to help you through this process, and that includes answering your questions and addressing your concerns. By staying informed and actively communicating with your doctors and nurses, you can become a confident partner in your prostate cancer care, even as you move into second-line treatments.

Sources:

1. National Cancer Institute (NCI) – Hormone Therapy for Prostate Cancer (Fact Sheet)​. This source explains how prostate cancer initially responds to hormone therapy and how it can become resistant, requiring additional treatments. It also details common side effects of hormone therapy, such as sexual changes, hot flashes, and bone effects.
2. NCI – Prostate Cancer Treatment (PDQ®) – Patient Version​. This source provides patient-friendly information on treatments like abiraterone and anti-androgens. It notes that abiraterone is used when prostate cancer has not improved with other hormone therapy and describes how anti-androgens block the action of male hormones like testosterone.
3. MedlinePlus (U.S. National Library of Medicine) – Drug Information for Enzalutamide, Apalutamide, Darolutamide, and Abiraterone​​. These sources describe in simple terms how each medication works and what it is used for. For example, they explain that enzalutamide, apalutamide, and darolutamide are androgen receptor inhibitors that “block the effects of androgen (a male hormone) to stop the growth and spread of cancer cells.” They also note that abiraterone is an androgen biosynthesis inhibitor that lowers the amount of certain hormones in the body.
4. NCI – Cancer Currents blog (Jan 2025)​. This article discusses modern prostate cancer treatments. It clearly states that drugs like abiraterone, apalutamide, darolutamide, and enzalutamide “stop cancer cells from using any testosterone that remains in the body.” This reinforces how second-line hormone therapies work following standard androgen deprivation.
5. National Cancer Institute – Castration-Resistant Prostate Cancer Treatment​. The NCI notes that men on long-term hormone therapy are regularly tested for PSA levels to monitor effectiveness, and that even with new treatments, ADT (testosterone-lowering therapy) is continued to keep hormones low. This supports the importance of ongoing monitoring and combined therapy approach.