“The Role of Testosterone in the Body: Effects, Deficiencies, and Excesses”

The conversion of testosterone, the main product of testicular steroidogenesis ensures 95% of the concentration of this androgen in men and involves a sequence of enzymatic reactions for the hydroxylation of dihydrotestosterone and the activation of 5α reductase in the skin and urogenital tract.

After synthesis, testosterone circulates in a majority proportion in the form bound to albumin 54% and sex hormone binding globulin 44%, and the remaining 1-2% is found in the blood level in free form. Unlike the female sex, in which steroidogenesis is stopped by the onset of menopause, the steroidogenesis function of the male gonads gradually decreases with age, but is not completely interrupted.

In women, steroidogenesis takes place at the level of the adrenal glands, the thecal cells (the morphofunctional unit of the ovary), secondary interstitial cells (derived from the sheath) and those derived from the hilum.

After synthesis, testosterone subsequently passes through diffusion from the level of thecal cells to the granulosa cells where it undergoes a series of enzymatic transformations as a result of which estrogen is finally obtained. The ovary is responsible for the synthesis of 2/3 of the circulating testosterone, of which 1/3 takes place in the thecal cells and the other half is obtained through the peripheral conversion of ovarian androstenedione.

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What role does testosterone play in the body?

The main roles of testosterone in women are represented by:

• The development of the mesonephric Wolff ducts during intrauterine life – the Wolff ducts constitute embryonic structures from which the male genital organs later develop.
• Growth and development of the larynx during puberty
• Increasing muscle mass
• Growth and development of the bone system
• Stimulation of erythropoiesis (erythrocyte synthesis)
• Inhibition of mammary gland development
• Libido stimulation
• Increase the development of the reproductive genitals.

Testosterone supports the male phenotype in all the specific stages of the individual’s development from birth to adulthood through:

• The masculinization of the internal and external genital organs that gives the genital sex at birth.
• Defining sexual characteristics and increasing height and muscle mass at puberty
• Maintaining male sexual characteristics in adult life.

The main metabolic effects of testosterone are represented by the decrease in the uptake of lipids at the tissue level with the induction of lipolysis and the decrease in the formation of adipocyte precursor cells, the increase in the rate of basal metabolism and the consumption of glucose at the tissue level.

In women, the testosterone generated by the ovary and adrenal glands has the role of supporting ovarian function, maintaining the integrity of the bone system and modulating sexual behavior by ensuring a normal libido.

What happens when the testosterone level in men is low?

The decrease in serum levels of testosterone in men can cause the appearance of specific clinical manifestations depending on the moment when androgen deficiency sets in, as follows:

• Prepubertal male hormone deficiency is responsible for the insufficient development of secondary sexual characteristics, the appearance of eunuchoid proportions, the absence of body hair and the late closure of linear growth cartilages.
• The low level of testosterone that occurs after the onset of puberty causes the appearance of minimal clinical manifestations, with multiple suggestive symptoms:
• Reduction of muscle mass
• Loss of body hair
• Depressive state
• Concentration difficulties
• Erectile dysfunction
• Decreased libido
• Osteoporosis (reduction of bone density).

What causes the testosterone level to decrease?

Low levels of testosterone in the case of men can be the primary cause and manifests itself in the form of hipogonadism primar which may be due to:

• Chromosomal abnormalities that cause Klinefelter syndrome.
• Cryptorchidism (the testicles do not descend to the level of the scrotum and do not ensure the synthesis of testosterone)
• Viral infections with the howling virus, which favors the appearance of orchitis and the decrease in the function of testicular steroidogenesis.
• Hemochromatosis in the evolution of which the increased levels of circulating iron determine the impairment of the regulatory capacity exercised by the pituitary gland on the testicular function of steroidogenesis.
• Testicular lesions with impairment of steroidosynthesis capacity at the level of Leydig cells.
• Oncological treatments that affect all cells with a rapid rate of growth and development, including those of the male reproductive system.

Secondary hypogonadism it is determined by the conditions of the pituitary gland or the hypothalamus (structures of the nervous system involved in the regulation of testosterone) and is frequently due to:

• Kallmann syndrome manifested by an abnormal development of some areas in the brain that control the synthesis of pituitary hormones.
• Pituitary gland dysfunctions caused by brain tumors or local chemo and radiotherapy treatments to treat them.
• Inflammatory conditions such as sarcoidosis, histiocytosis and tuberculosis involving the pituitary gland.
• The administration of certain types of drug treatments such as potassium-sparing diuretics or analogues of gonadotropin release hormone.
• Infection with the human immunodeficiency virus HIV/AIDS that can affect the function of the pituitary gland and the hypothalamus.

The physiological decrease of testosterone synthesis in men begins after the 4th decade of life and shows a rate of approximately 1%/year, being influenced by:

• Chronic alcohol consumption
• Excess weight
• Metabolic syndrome
• Diabetes mellitus
• Sedentary lifestyle.

What happens when the level of testosterone in men is high?

The increase in serum testosterone concentrations in men can be clinically manifested by the following signs and symptoms:

• Phenotypic changes that include excessive body hair, early baldness (baldness), increased Adam’s apple size.
• Mood changes that include irritability, anxiety, depression and decreased sexual appetite.
• Speech disorders (slurred or difficult speech).
• Changes in blood pressure (hypotension or hypertension).
• Peripheral edema.
• Headache, feeling of dizziness and severe fatigue.
• Erectile dysfunction.
• Male infertility.
• Increased appetite with excess weight gain.
• Sleep disorders manifested by insomnia.

The increase in the concentration of serum testosterone represents a important risk factor for the occurrence of acute cardiovascular events (heart attack or stroke), deep vein thrombosis, pulmonary embolism, benign prostatic hyperplasia and sleep apnea.

What causes the testosterone level to increase?

The main causes favoring the increase in the serum level of testosterone in men are represented by:

• Testicular or adrenal gland tumors.
• Administration of anabolic steroids to improve physical condition.
• The use of androgenic supplements in hormone replacement therapy.

Increased serum testosterone concentrations in females is frequently associated with:

• Tumor diseases of the adrenal glands and the ovary
• Polycystic ovary syndrome
• Congenital adrenal hyperplasia
• Use of anabolic steroids.

Normal testosterone values ​​according to age

Normal testosterone values ​​vary according to age and are included in the following biological reference ranges:

How is the blood testosterone level measured?

Determination of serum testosterone values ​​is performed from blood collected by peripheral venipuncture with the patient fasting. Testosterone synthesis shows episodic, circadian and cyclic variations, so it is recommended to collect 3 different blood samples at an hourly interval, and to determine the hormone from the sum of the 3 serums obtained after centrifuging the vacutainers.

References:

• A Brief History of TestosteroneErica R. Freeman, David A. Bloom, edward J. McGuire, American Urological Association
• Testosterone Treatment and Mortality in Men with Low Testosterone LevelsMolly M. Shores, Nicholas L. Smith, Christopher W. Forsberg, Bradley D. Anawalt, Alvin M. Matsumoto, Oxford Academic – The Journal of Clinical Endocrinology & Metabolism
• The role of testosterone in social interactionChristoph Eisenegger, Johannes Haushofer, Ernst Fehr
• Total TestosteroneCenters for Disease Control and Prevention