Premature Ejaculation: Causes and Treatments

Testosterone Across the Lifespan: Physiology, Imbalance, and Clinical Meaning

Testosterone is commonly described as a “male hormone”, yet its role is broader, more nuanced, and clinically more important than this shorthand suggests. It is an androgen present in both men and women, synthesized from cholesterol under the control of the hypothalamic–pituitary–gonadal axis, and essential for sexual development, metabolic balance, musculoskeletal integrity, erythropoiesis, and psychological well-being.

Rather than functioning in isolation, testosterone acts within a tightly regulated hormonal network. Deviations, whether too low or too high, are rarely benign and often signal systemic disease, metabolic stress, or endocrine dysregulation.

How Testosterone Is Produced and Circulates

In men, testosterone is synthesized primarily in the testes by Leydig cells, under stimulation by luteinizing hormone secreted from the pituitary gland. Cholesterol serves as the universal substrate for steroidogenesis, entering Leydig cells where a specific enzymatic cascade converts it into testosterone.

Testicular production accounts for approximately 95% of circulating testosterone in men. After synthesis, testosterone is released into the bloodstream, where it circulates largely in bound form:

• about 54% bound to albumin,

• roughly 44% bound to sex hormone-binding globulin (SHBG),

• only 1–2% remains unbound as free testosterone, the biologically active fraction.

In contrast to women, whose ovarian steroidogenesis ceases at menopause, male gonadal function declines gradually with age but is not abruptly interrupted.

In women, testosterone is produced by the adrenal glands, ovarian theca cells, secondary interstitial cells, and cells of the ovarian hilum. A substantial portion of female testosterone arises from peripheral conversion of androstenedione. Within the ovary, testosterone also serves as a precursor for estrogen synthesis, undergoing aromatization in granulosa cells.

The Physiological Role of Testosterone

In Male Development and Adult Function

Testosterone shapes the male phenotype from early fetal life through old age. During intrauterine development, it drives masculinization of the internal and external genital organs. At puberty, it induces the growth of the larynx, voice deepening, linear growth acceleration, increased muscle mass, and development of secondary sexual characteristics.

In adulthood, testosterone maintains:

• muscle mass and strength,

• bone density,

• libido and erectile function,

• sperm production,

• erythropoiesis,

• metabolic efficiency, by promoting lipolysis and limiting adipocyte formation.

At the metabolic level, testosterone reduces lipid uptake into adipose tissue, increases basal metabolic rate, and improves glucose utilization, linking androgen status directly to cardiometabolic health.

In Women

Although present in much lower concentrations, testosterone in women plays a critical role in ovarian physiology, bone integrity, muscle tone, energy levels, and sexual desire. Both deficiency and excess can significantly impair quality of life and reproductive function.

Consequences of Low Testosterone in Men

The clinical impact of androgen deficiency depends strongly on the timing of onset.

When testosterone deficiency occurs before puberty, it results in incomplete sexual maturation, absent or sparse body hair, delayed epiphyseal closure, and eunuchoid body proportions.

When deficiency develops after puberty, manifestations are often subtler but clinically significant. Men may experience progressive loss of muscle mass, reduction of body hair, decreased libido, erectile dysfunction, low mood, impaired concentration, fatigue, and reduced bone mineral density leading to osteoporosis.

Importantly, low testosterone rarely exists in isolation. It often coexists with obesity, insulin resistance, metabolic syndrome, and cardiovascular disease, forming a self-reinforcing pathological loop.

Why Testosterone Levels Decline

Primary Hypogonadism

Primary hypogonadism originates at the level of the testes and includes conditions such as chromosomal abnormalities like Klinefelter syndrome, undescended testes, viral orchitis, iron overload disorders, direct testicular injury, and gonadotoxic oncological treatments.

In these situations, Leydig cell function is impaired despite intact pituitary signaling.

Secondary Hypogonadism

Secondary hypogonadism reflects dysfunction of the hypothalamus or pituitary gland. It may arise from congenital syndromes affecting gonadotropin secretion, pituitary tumors, inflammatory or infiltrative diseases, infections such as HIV, or medications that suppress gonadotropin release.

Age-Related and Lifestyle-Associated Decline

From the fourth decade onward, testosterone levels decrease at an average rate of about 1% per year. This decline is strongly influenced by modifiable factors including excess body weight, chronic alcohol consumption, physical inactivity, diabetes, and metabolic syndrome. In many cases, lifestyle change can partially restore androgen levels without pharmacological intervention.

When Testosterone Levels Are Excessive

Elevated testosterone levels are not protective and can be clinically harmful. In men, excess testosterone may present with mood instability, irritability, sleep disturbances, infertility, erectile dysfunction, edema, blood pressure fluctuations, and increased cardiovascular risk. Sustained elevation is associated with thromboembolic events, prostate enlargement, and sleep apnea.

In women, elevated testosterone is commonly linked to endocrine disorders such as polycystic ovary syndrome, congenital adrenal hyperplasia, or hormone-secreting tumors, leading to hirsutism, acne, menstrual irregularities, and infertility.

Normal Testosterone Values and Their Interpretation

Testosterone reference ranges vary with age and laboratory methodology. Both total testosterone and free testosterone must be interpreted in clinical context, alongside SHBG levels, symptoms, and comorbidities. Age-related changes are physiological, but values falling below reference ranges in symptomatic individuals warrant evaluation.

Importantly, a single measurement is insufficient. Testosterone secretion follows circadian and pulsatile patterns, peaking in the morning. Accurate assessment requires fasting blood sampling, ideally repeated on separate occasions.

Measuring Testosterone Correctly

Serum testosterone is measured from venous blood, collected in the morning after fasting. Because of biological variability, repeated measurements are recommended. Free testosterone estimation and SHBG assessment are often necessary, particularly in older men or those with obesity, liver disease, or thyroid dysfunction.

Interpretation should always be integrated with clinical findings rather than used in isolation.

Scientific References

1. Vermeulen A. Declining androgens with age. Androgens and the Aging Male. Parthenon Publishing.

2. Freeman ER, Bloom DA, McGuire EJ. A brief history of testosterone. American Urological Association.

3. Shores MM et al. Testosterone treatment and mortality in men with low testosterone. Journal of Clinical Endocrinology & Metabolism.

4. Eisenegger C et al. The role of testosterone in social interaction. Trends in Cognitive Sciences.

5. Centers for Disease Control and Prevention. Total testosterone reference data.