Understanding Male Hormonal Health, testosterone Decline and Hormone Replacement Therapy

The controversies regarding the andropause

What is the andropause?

Male testosterone levels tend to reduce in later life, and these may be associated with reduced vitality, sexual function, mood, and energy levels.

What are the signs and symptoms of Andropause?

Male hormonal health is a  component of overall wellness, influencing physical strength, energy, mood, and sexual health. As men age, hormonal shifts—most notably a gradual decline in testosterone levels—become more common. This process, sometimes referred to as "andropause," has physical and mental effects that often prompt men to explore treatments Testosterone replacement therapy (TRT) to restore balance and alleviate symptoms.

Testosterone Decline and its Effects on Health

Testosterone, the primary male sex hormone, plays a significant role in developing muscle mass, bone density, red blood cell production, and sexual function. Starting around age 40, testosterone levels in men naturally begin to decline at an average rate of about 1% per year. For some, this drop can be pronounced, resulting in:

Physical Symptoms: Low testosterone can lead to decreased muscle mass, increased body fat (particularly in the abdomen), reduced bone density, and low energy levels. It can also contribute to metabolic changes, which may lead to weight gain and a higher risk of conditions like cardiovascular disease and type 2 diabetes.

Mental Health Symptoms: Testosterone influences brain function, impacting mood, cognition, and emotional well-being. Men experiencing testosterone decline may report mood swings, anxiety, low motivation, irritability, and even depressive symptoms.

Sexual Health: Declining testosterone can lead to reduced libido, erectile dysfunction, and a lower overall interest in sex, which can impact intimate relationships and self-esteem.

Is the andropause classed as a condition?

Sex hormone function is a complex process, associated with obesity, diabetes, metabolic syndrome, and the side effects of medication. The notion of andropause remains controversial. There has been a huge increase in testosterone replacement therapy (TRT) being administered to elderly men over the last few decades, however this cannot be ascribed to any new scientific evidence. The andropause has been described as a fabricated condition (1), exploiting an unjustifiable and unachievable desire for revitalisation and an over medicalisation of aging. Andropause is a catchy phrase, but as a description, it is a poor term. There is no sudden drop in testosterone production or loss of fertility that is seen in menopause. There are fundamental differences between TRT and HRT in women but there is also some symmetry in the nature of the risk benefits profile, when assessing the cardiovascular risk, and the risk of prostate cancer in men and breast cancer in women.

TRT for erectile dysfunction

TRT can be advocated for erectile dysfunction in aging men with low testosterone, however only a small proportion of men with erectile dysfunction have low testosterone and many men will have normal erectile function with slightly reduced testosterone levels. Overall phosphodiesterase type 5 inhibitors such as Cialis (tadalafil) or Viagra (Sildenafil) are more effective.

TRT vs HRT, Andropause versus the menopause

The idea of TRT for improved vitality is more controversial and frowned upon by some. This may be unfair and there may be a double standard being applied. HRT for women is often promoted as a means of restoring vitality and general health including preventing osteoporosis, bone mineral strength and libido. There are differences too, women may suffer severe menopausal symptoms, off hot flushes, night sweats which men never usually experience as there is usually no drastic decline in testosterone levels. This side effect is usually only experienced in men who are receiving hormonal treatment for prostate cancer that suppresses testosterone levels, through either peripheral androgen receptor inhibitors such as bicalutamide or gonadotropin release agonists such as Zoladex.

Administering testosterone results in negative feedback on the pituitary and the hormones FSH and LH. These hormones stimulate spermatogenesis and testosterone by the testicle, so TRT can impair fertility and testicular function and this suppression of the pituitary gland can be longer term, such that patients may become dependent on TRT as their own production of testosterone may become suppressed. There is no such concern after the menopause in women, as ovarian function has permanently ceased, and oestrogen production is in a permanently low state. Some low-level oestrogen synthesis continues, via aromatase conversion of ovarian androstenedione to estrone. Obesity leads to increased aromatase activity and is associated with higher oestrogen and testosterone level (2).

Risks and Considerations of Testosterone Replacement Therapy (HRT) for Men

While Testosterone Replacement Therapy (TRT) can improve symptoms of low testosterone, it also presents potential risks that require careful consideration and ongoing monitoring. Here’s a closer look at the main risks, potential complications, and the monitoring protocols needed to ensure safe and effective treatment.

1. Cardiovascular Health Risks

One of the most widely debated risks associated with TRT for men is its potential effect on cardiovascular health. Some studies have suggested that TRT could increase the risk of heart disease, heart attack, or stroke, though findings are mixed, and newer research is increasingly nuanced. It appears that the cardiovascular impact of TRT may depend on the individual’s baseline health status, age, dosage, and delivery method.

Monitoring and Prevention: Routine cardiovascular monitoring is recommended for men undergoing TRT, including regular checks of blood pressure, cholesterol, and triglycerides. For those with pre-existing heart conditions, a thorough cardiovascular assessment is essential before starting TRT.

2. Prostate Health Concerns

Testosterone can stimulate prostate tissue growth, raising concerns that TRT could potentially accelerate prostate cancer growth. While there is no conclusive evidence that TRT causes prostate cancer, it may aggravate an existing undiagnosed cancer or benign prostate enlargement (BPH). For this reason, men considering TRT are advised to undergo prostate screenings.

Monitoring and Prevention: Men should have a baseline prostate-specific antigen (PSA) test and digital rectal exam (DRE) before beginning TRT, with follow-up PSA tests every 3 to 6 months. Elevated PSA levels may prompt further evaluation to rule out cancer or other prostate health issues.

3. Polycythaemia (Increased Red Blood Cell Production)

Testosterone therapy can stimulate erythropoiesis, or red blood cell production, which can lead to polycythaemia—a condition characterized by an abnormally high concentration of red blood cells. This increases blood viscosity and can elevate the risk of blood clots, potentially leading to deep vein thrombosis (DVT), pulmonary embolism, or stroke.

Monitoring and Prevention: Regular blood tests, particularly haematocrit levels, should be conducted every 3 to 6 months. If haematocrit levels become too high, the provider may reduce the dosage, adjust the administration frequency, or temporarily pause TRT.

4. Sleep Apnoea

Sleep apnoea, a condition in which breathing intermittently stops during sleep, can be exacerbated by testosterone therapy. For men with existing sleep apnoea or a higher risk of developing it, HRT could worsen symptoms. Sleep apnoea not only disrupts rest but also increases the risk of cardiovascular issues and other health complications.

Monitoring and Prevention: Men with known sleep apnoea or symptoms (such as loud snoring, gasping during sleep, or excessive daytime fatigue) may need a sleep study before beginning TRT. Continuous Positive Airway Pressure (CPAP) machines or other therapies may be recommended to manage sleep apnoea if TRT is pursued.

5. Infertility

TRT can suppress the body’s natural production of testosterone, which is essential for sperm production, potentially leading to infertility. For men planning on fathering children, this is a critical consideration, as HRT could make conception difficult or even impossible during treatment.

Monitoring and Prevention: Alternative treatments, such as selective oestrogen receptor modulators (SERMs) or gonadotropin injections, may be considered for men who wish to preserve fertility. Men undergoing TRT should also have a conversation with their healthcare provider about family planning and potential sperm preservation options.

6. Mood Changes and Mental Health

While TRT can improve mood in many men with low testosterone, it can sometimes have the opposite effect, causing mood swings, irritability, or even anxiety. The hormone fluctuations associated with TRT may initially exacerbate symptoms before stabilizing, which can affect mental health.

Monitoring and Prevention: Mental health monitoring, particularly during the first few months of TRT, is important. Men should communicate any emotional changes to their healthcare provider, who can adjust dosages as needed. Lifestyle adjustments, therapy, or counselling may also be beneficial for managing any psychological effects.

7. Gynecomastia (Breast Tissue Enlargement)

In some men, testosterone can be converted into oestrogen in the body, leading to gynecomastia, or the development of enlarged breast tissue. This is generally more common in men with higher body fat percentages, as fat tissue can facilitate the conversion of testosterone to oestrogen.

Monitoring and Prevention: Regular physical exams can help detect early signs of gynecomastia. Adjustments in testosterone dosage or adding aromatase inhibitors (which block oestrogen conversion) may be considered if gynecomastia becomes a concern.

8. Liver Health Considerations (Especially with Oral Testosterone)

Oral testosterone can cause liver strain over time. This risk is specific to oral formulations, as they are metabolized in the liver. While most testosterone therapies avoid oral formulations to bypass this risk, it’s important to be aware of liver health with any type of hormone therapy.

Monitoring and Prevention: For those using any oral testosterone supplements (though rare), regular liver function tests are necessary. Most providers recommend other delivery forms—like gels, patches, or injections—that bypass the liver entirely.

Comprehensive Monitoring Protocol for TRT

For men undergoing TRT, regular and thorough monitoring is crucial to ensure both the efficacy and safety of the treatment. Recommended monitoring guidelines include:

Blood Tests Every 3-6 Months: Monitoring testosterone levels, hematocrit, hemoglobin, liver enzymes, and PSA levels.

Cardiovascular Monitoring: Blood pressure checks and cholesterol panels are typically recommended to prevent cardiovascular complications.

Prostate Health Exams: Regular PSA tests and digital rectal exams help in tracking prostate health.

Bone Density Tests (for Older Men): Bone density scans can be valuable for men who are at risk of osteoporosis, especially if TRT is used long-term.

Mental Health Check-ins: Ongoing communication about emotional and mental health symptoms is important, particularly in the initial stages of TRT.

Conclusion

While Hormone Replacement Therapy can be therapeutic for restoring sexual function, vitality, energy, and mental well-being, it also comes with specific risks that require vigilant monitoring and personalized treatment planning. Men considering TRT should consult with a knowledgeable healthcare provider to weigh these risks, discuss family planning considerations, and set up a comprehensive monitoring schedule.

Concerns over TRT mirror those of HRT in women with the increased risk of blood clots and breast cancer which have led to more judicious and tempered use of HRT in more recent years. HRT in women seems to be safer below the age of 60, when the risk of cardiovascular disease and stroke are reduced and is only taken for as long as needed, typically limited to 5 years.

There are still many gaps in our knowledge regarding the risk and benefits of HRT and TRT and there are natural alternatives to supporting hormonal health.

Lifestyle Tips to Naturally Support Hormonal Health

For men who prefer to manage testosterone levels naturally or have only mild symptoms, lifestyle changes can provide noticeable benefits:

Exercise Regularly: Strength training and HIIT workouts boost testosterone.

Get Quality Sleep: Aim for 7-8 hours per night to support healthy testosterone production.

Balanced Nutrition: A diet rich in protein, healthy fats, and vitamins (particularly vitamin D and zinc) helps regulate testosterone.

Stress Management: Chronic stress elevates cortisol, which can suppress testosterone. Techniques like mindfulness, yoga, and meditation can help.

Limit Alcohol and Avoid Smoking: Both can negatively affect testosterone levels over time.