Hormones – Disorders & Treatment: Testosterone Deficiency, TRT, Hormonal Disorders & Andropause

Testosterone Deficiency (Hypogonadism)

Testosterone is the central male sex hormone and regulates muscle mass, bone density, libido, mood, erythropoiesis, and spermatogenesis. A persistently reduced testosterone level – referred to as hypogonadism – can have a significant impact on both body and mind.

A distinction is made between primary and secondary hypogonadism, based on where the disorder is located. In primary hypogonadism, the cause lies in the testes themselves: the Leydig cells produce insufficient testosterone despite adequate stimulation by LH. Causes include congenital conditions such as Klinefelter syndrome, testicular trauma, radiation, inflammatory diseases such as mumps orchitis, or drug-induced damage. Secondary hypogonadism (hypogonadotropic hypogonadism) results from insufficient stimulation of the testes due to a disorder at the hypothalamic or pituitary level: too little GnRH or too little LH/FSH results in reduced testicular activity. Causes include tumors (e.g. prolactinoma), chronic stress, obesity, diabetes mellitus, certain medications, and alcohol or substance abuse. In practice, mixed pictures are common, for example in older men, in whom both testicular and central factors contribute.

Symptomatically, testosterone deficiency manifests as loss of libido, erectile dysfunction, decreased muscle mass and physical strength, increased abdominal fat, reduced body and facial hair, osteoporosis, fatigue, lack of drive, depressive moods, difficulty concentrating, and sleep disturbances. Not all symptoms need to occur at the same time; the clinical picture is often nonspecific and requires systematic evaluation.

Diagnosis is based on the combination of clinical symptoms and a laboratory-confirmed low serum testosterone level. Blood should be drawn in the morning, between 7 and 10 a.m., as testosterone levels follow a daily rhythm and are highest in the morning. Depending on the clinical situation, free testosterone, SHBG, LH, FSH, prolactin, and other parameters are measured in addition to total testosterone. A low laboratory value alone, without a matching clinical picture, is not an indication for treatment.

Testosterone Replacement Therapy (TRT)

In cases of confirmed, symptomatic hypogonadism, testosterone replacement therapy is the treatment of choice. It replaces the missing testosterone exogenously and leads to a marked improvement in symptoms for most patients – libido, energy, mood, muscle mass, and bone density have all been shown to improve under adequate TRT.

Delivery methods are varied: transdermal gels or creams, applied daily to the skin, offer stable levels with good controllability. Intramuscular injections – short-acting (testosterone enanthate every two to three weeks) or long-acting (testosterone undecanoate every ten to fourteen weeks) – are particularly suitable for patients with poor compliance. Transdermal patches and oral or buccal preparations are less commonly used alternatives.

TRT requires regular monitoring: testosterone levels, hematocrit (since testosterone stimulates erythropoiesis and can promote polycythemia), PSA and prostate volume, as well as blood count and lipid profile, are checked at defined intervals. Relevant contraindications include prostate cancer, male breast cancer, severe cardiac disease, and a markedly elevated hematocrit. In younger men wishing to have children, it is particularly important to note that exogenous testosterone supplementation suppresses endogenous sperm production through negative feedback on the pituitary gland; in this case, alternative treatment approaches such as gonadotropin-based stimulation therapy are preferable.

Andropause

Andropause – also referred to as late-onset hypogonadism or age-related hypogonadism – describes the physiological, age-related decline in testosterone levels in men. Unlike female menopause, which is marked by an abrupt drop in hormone levels, the decline in testosterone in men is slow and gradual – typically around one to two percent per year from the third decade of life onward. Clinically relevant symptoms usually appear between the ages of 45 and 60, though this can vary considerably from person to person.

The symptom picture of andropause overlaps with that of hypogonadism: declining libido and potency, fatigue, lack of drive, mood swings, loss of muscle mass, increased body fat, sleep disturbances, and, rarely, hot flashes. Because these symptoms are nonspecific and can also be caused by other conditions – depression, thyroid disorders, metabolic syndrome – a differentiated diagnostic workup is important before TRT is initiated.

Other Hormonal Disorders in Men

Besides hypogonadism, there are a number of more specific hormonal disorders that are relevant in andrology and endocrinology. Klinefelter syndrome (47,XXY) is the most common chromosomal cause of primary hypogonadism and is associated with infertility, reduced testosterone, gynecomastia, and, in some cases, limited testicular anatomy. Prolactinoma is a benign pituitary tumor that suppresses GnRH secretion through elevated prolactin levels, leading to secondary hypogonadism with loss of libido, erectile dysfunction, and infertility – drug treatment with dopamine agonists is highly effective in many cases. Kallmann syndrome is a rare genetic cause of secondary hypogonadism, combined with anosmia (absent sense of smell) due to abnormal migration of GnRH neurons. Congenital adrenal hyperplasia (CAH) leads, through enzymatic defects of the adrenal cortex, to overproduction of androgen precursors with wide-ranging clinical consequences. Hormone resistance syndromes – such as partial or complete androgen insensitivity – arise from defects in the androgen receptor and can lead to a feminine phenotype despite normal or elevated androgen levels. Finally, anabolic steroid abuse suppresses the body's own testosterone production through the negative feedback mechanism triggered by exogenous androgen intake, and can lead to permanent hypogonadism, testicular atrophy, infertility, and gynecomastia.