Bipolar androgen therapy (BAT) is an innovative cancer treatment strategy that involves unique hormonal fluctuations. This method uses precisely controlled shifts in hormone levels, differing from conventional approaches.
What is Bipolar Androgen Therapy?
Bipolar androgen therapy is a treatment strategy that involves intentionally cycling between very high, or supraphysiological, and very low, or near-castrate, levels of testosterone. This approach is primarily used for men whose prostate cancer has become resistant to standard androgen deprivation therapy (ADT), a condition known as castration-resistant prostate cancer (CRPC).
Standard ADT aims to lower testosterone to near-castrate levels (below 50 ng/dL) to inhibit cancer growth, as prostate cancer cells often rely on androgens for survival. Historically, androgen deprivation has been a foundational treatment for prostate cancer, often achieved through surgical castration or medications that suppress testosterone production. However, over time, prostate cancer cells can adapt to low androgen environments and resume growth, leading to CRPC. BAT emerges as a response to this resistance, seeking to re-sensitize these adapted cancer cells to hormonal manipulation.
How Bipolar Androgen Therapy Works
The mechanism of action for BAT involves a disruptive approach to prostate cancer cells, especially those that have adapted to low-androgen environments by increasing their androgen receptor (AR) expression. During the high-dose phase, supraphysiological levels of testosterone (often 1000–3000 ng/dL) are introduced, aiming to overwhelm the highly expressed AR pathway within these resistant cells. This sudden flood of androgen is thought to disrupt the cancer cells’ ability to divide and thrive, potentially leading to cell death or a state of growth arrest.
Following this high-dose exposure, the testosterone levels rapidly decline back to near-castrate levels, often remaining below 100-200 ng/dL by the end of the 28-day cycle, as patients continue concurrent androgen deprivation therapy. This rapid fluctuation prevents cancer cells from adapting to a single hormonal environment, keeping them in a state of disequilibrium. The subsequent low-dose phase may allow for recovery and potential re-sensitization of the cancer cells to androgen deprivation, making them more vulnerable to subsequent hormonal therapies. Some research suggests that high androgen levels can induce a quiescent, dormant state in cancer cells or lead to cell death by disrupting DNA replication licensing.
Who Can Benefit from Bipolar Androgen Therapy?
Bipolar androgen therapy is used for men with metastatic castration-resistant prostate cancer (mCRPC) who have experienced disease progression despite prior androgen-deprivation therapies. This means their cancer has spread beyond the prostate and continues to grow even with very low testosterone levels. Patients for BAT often have received at least one androgen receptor signaling inhibitor, such as abiraterone or enzalutamide, and in some cases, prior chemotherapy.
A patient’s overall health, including an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less, is also a consideration for eligibility. BAT is not a first-line treatment and is not recommended for men with symptomatic bone pain due to metastatic prostate cancer, as it can temporarily worsen this pain. Consultation with a physician is necessary to assess individual disease characteristics and determine suitability for this evolving therapeutic strategy.
Managing Bipolar Androgen Therapy
Bipolar androgen therapy involves an intramuscular injection of testosterone cypionate, often 400 mg, administered every 28 days, while continuous androgen deprivation therapy is maintained. This regimen causes serum testosterone levels to rapidly increase to supraphysiological levels (e.g., 1000–3000 ng/dL) and then gradually decline to near-castrate levels before the next injection. Monitoring prostate-specific antigen (PSA) levels frequently, perhaps every two weeks to once a month, is important to track treatment effectiveness.
Common side effects associated with BAT are mild to moderate and can include hot flashes, breast tenderness, generalized muscle aches, and swelling in the lower legs. Some men report improved quality of life, including increased energy, libido, and even restoration of sexual function, which can be significant after prolonged androgen deprivation.
However, the main concern is uncontrolled cancer growth, which could manifest as worsening bone pain, although this is usually due to inflammatory factors rather than rapid tumor growth. While not a cure, BAT has shown promise in inducing PSA responses and tumor regression in some patients, potentially sensitizing them to subsequent androgen receptor inhibitor therapies.