Treatise Index
It's Not "Male Menopause"
The term "Andropause" is scientifically incorrect. Unlike women, who cease ovarian function abruptly, men experience a gradual and variable decline in testosterone. The correct term is ADAM (Androgen Deficiency in the Aging Male) or Late-Onset Hypogonadism, characterized by the triad: low testosterone levels + clinical symptoms + absence of other explanatory pathology.
1. Introduction: The Myth of Eternal Virility
Testosterone is much more than a sex hormone; it is a fundamental systemic metabolic modulator for bone, muscle, cognitive, and cardiovascular health. With increasing life expectancy, the management of male aging has become a central theme in modern medicine.
ADAM affects approximately 20% of men over 60 years old and up to 50% of those over 80. However, diagnosis is often overlooked, with symptoms erroneously attributed solely to "getting old" or treated in isolation (e.g., antidepressants for fatigue or Viagra for erectile dysfunction) without investigating the hormonal root cause.
2. Hypothalamic-Pituitary-Gonadal Axis Physiology
Testosterone production is orchestrated by a precise negative feedback system:
- Hypothalamus: Secretes GnRH (Gonadotropin-Releasing Hormone) in a pulsatile manner.
- Pituitary: Responds to GnRH by releasing LH (Luteinizing Hormone) and FSH (Follicle-Stimulating Hormone).
- Testes: LH stimulates Leydig Cells to synthesize testosterone from cholesterol. FSH regulates spermatogenesis in Sertoli Cells.
In the blood, only about 2% of testosterone circulates free (active). The rest is bound to albumin (38%) or strongly bound to SHBG (60%). Aging increases SHBG, further "sequestering" the hormone and reducing the bioavailable fraction.
3. The Decline: The 1% per Year Rule
Starting from age 30-40, total testosterone levels physiologically fall at an average rate of 1% to 2% per year. However, lifestyle factors can dramatically accelerate this process.
Obesity is the biggest villain. Adipose tissue contains the enzyme aromatase, which converts testosterone into estradiol (estrogen). High estradiol inhibits the axis at the hypothalamus, further reducing testosterone production, creating a vicious cycle of weight gain and functional hypogonadism.
4. Clinical Symptoms: The ADAM Picture
Symptoms are insidious and nonspecific, generally grouped into three domains:
| Domain | Signs and Symptoms |
|---|---|
| Sexual | Loss of libido (desire), erectile dysfunction (especially loss of morning erections), difficulty achieving orgasm. |
| Physical/Somatic | Chronic fatigue, loss of muscle mass (sarcopenia), increased visceral fat, osteoporosis, decrease in body hair. |
| Psychological | Irritability, depression, sleep disturbances, loss of memory and concentration ("brain fog"). |
5. Precise Laboratory Diagnosis
ADAM is not diagnosed with just one test. The Endocrine Society guidelines require:
- Two morning measurements: Testosterone has a circadian rhythm (peak between 7am-9am). Collections made in the afternoon can be falsely low in young men (although this rhythm attenuates in the elderly).
- Free Testosterone: Total testosterone may be normal, but free testosterone low (due to high SHBG). Calculated Free Testosterone (using the Vermeulen formula) is more reliable than direct measurement by analog methods.
- Exclusion of Reversible Causes: Hyperprolactinemia, hypothyroidism, sleep apnea, and medication use (corticosteroids, opioids) must be ruled out.
6. Impact on Metabolic Syndrome and Bones
Low testosterone is an independent marker of death risk. Men with hypogonadism have a higher prevalence of:
- Insulin Resistance and Type 2 Diabetes: Testosterone improves muscle glucose uptake.
- Cardiovascular Disease: Deficiency is associated with an atherogenic lipid profile and endothelial dysfunction.
- Male Osteoporosis: Testosterone is locally converted to estrogen in the bone, essential for mineralization. Hip fractures in men have higher mortality than in women.
7. Testosterone Replacement Therapy (TRT)
TRT is not for aesthetic purposes, but for physiological restoration. Administration routes include transdermal gels (more physiological, mimicking the daily rhythm) and long or short-acting injectables (undecanoate, cypionate).
Proven Benefits
- Improved body composition (less fat, more muscle).
- Increased bone mineral density.
- Improved libido and sexual function.
- Improved mood and mild depressive symptoms.
Risks and Monitoring
- Erythrocytosis (Thick blood): Testosterone stimulates erythropoiesis. Hematocrit > 54% requires dose adjustment or therapeutic phlebotomy.
- Infertility: Exogenous TRT suppresses LH/FSH, paralyzing sperm production. Men who desire children should avoid testosterone and opt for stimulants like Clomiphene or HCG.
8. The Prostate Myth and Safety
For decades, it was believed that "testosterone caused prostate cancer." Modern studies have debunked this myth. The saturation theory proposes that the prostate is sensitive to androgens only up to very low levels; above that, receptors are saturated and additional levels do not stimulate tumor growth.
However, TRT is contraindicated in patients with active or untreated metastatic prostate cancer.
9. Conclusion
ADAM is a serious clinical condition that impacts longevity and quality of life. Testosterone Replacement Therapy, when well-indicated and monitored, is safe and effective. The decision to treat should be individualized, weighing risks and benefits, and always accompanied by lifestyle changes, such as weight loss and resistance exercise, which can naturally raise hormone levels.