Dr. O.P.Sharma writes in detail on PADAM or Partial Androgen (Testosterone) Deficiency, andropause in men typically occurring post-50s, options for testosterone replacement therapy, and adverse reactions patients may encounter.

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In elderly men, the decline in androgen levels which occur with age is commonly known as andropause. Andropause occurs in approximately 1 in 200 men, usually in the mean age group of 50-60. [1]

A World Health Organization report states that “male androgens progressively decline with age”. Androgen levels at the age of 70 years maybe only 10% of what they are during youth.

Men do not experience rapid total cessation of Leydig cell or seminiferous tubule function with old age. However male sexual function does decrease with age. Starting at about age 30, testosterone levels drop by about 10% every decade. After the age of 40 years, total and free testosterone levels decline by 1and 1 to 2% per year respectively. [2]

PADAM or Partial Androgen (Testosterone) Deficiency in the Ageing Male is a clinical condition characterised by changes in attitude and moods, fatigue, loss of energy and sex drive. [3]

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Normal physiology

Testosterone is the male hormone that is mainly a product of the testis. Cholesterol is the precursor steroid and the production of testosterone is regulated by the pituitary as well as testosterone itself. Although testosterone is the major product, androsterone, androstenedione, progesterone and pregnenolone are also secreted by the testis. The major sites of formation and action of dihydrotestosterone are extra glandular. Androstenedione serves as a precursor for extra glandular oestrogen formation.

Testosterone exists in the free and bound forms. The free form is the one responsible for biological actions. Around 97 to 98% of testosterone is in the bound form, most of it is bound to SHBG (Sex Hormone Binding Globulin). In the blood, about 2% of testosterone is free.

Testosterone also serves as a circulating precursor for the formation of two types of active metabolites. It can undergo irreversible reduction to a 5α-reduced steroid or can be aromatized to estrogens. Thus, the physiological actions of testosterone are the result of the combined effects of testosterone and its metabolites.

Mechanism of androgen decline include diminished testicular secretory capacity. There is an altered neuroendocrine regulation of the Leydig cells with the apparent failure of the feedback mechanisms to fully compensate and there is an independent increase of SHBG binding capacity.

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Role of testosterone

• Brain (Mild Cognitive Impairment, Alzheimer)
• Heart (Premature IHD)
• Muscles (Loss of muscle mass)
• Bone (Osteoporosis)
• Genitalia (Hypogonadism)

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Effects of testosterone deficiency

In the ageing male, endocrine changes and a decline in endocrine function involve tissue responsiveness as well as reduced secretory output from peripheral glands and alterations in the central mechanism controlling the temporal organisation of hormonal release. These are in part responsible for the age-dependent decrease of the peripheral levels of testosterone, dehydroepiandrosterone (DHEA), the thyroid hormones, growth hormone (GH), IGF1 and melatonin. These hormonal changes, which develop in most men at about the age of 50, are in part responsible for the endocrine deficiencies of some older men.

One of the best-studied endocrine deficiencies is late-onset hypogonadism or andropause. This is a syndrome characterised by adverse effects on multiple organ systems and decreased quality of life, associated with advancing age and characterised by signs and symptoms of hypogonadism and a deficiency in serum androgen levels with or without a decreased genomic sensitivity to androgens.

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Effects of testosterone

Testosterone plays a vital role in the formation of male phenotype during sexual differentiation. This leads to the promotion of sexual maturation at puberty. This is also responsible for the initiation and maintenance of spermatogenesis and control of sexual drive and sex potential. This hormone has its effects on the metabolic activities and maintenance of muscle mass.

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Clinical manifestations

Low bioavailability of testosterone affects the body in a very insidious way. Hence, it may be initially missed as side effects of some of the chronic illnesses/co-morbidities or changing lifestyle. However, on suspicion and when asked, patients mention low sex drive and decreased sexual performance or erectile dysfunction. They also suffer from decreased muscle mass and strength, and unexplained fatigue. The other symptoms include increased anxiety, emotional, psychological and behavioural changes, insomnia and forgetfulness. Gynecomastia draws attention frequently but may be ignored even by a clinician. It can also put men at risk of cardiovascular problems and osteoporosis, impairment of cognitive function and an increased risk of Alzheimer's disease.

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Diagnosis

Andropause is diagnosed clinically and is usually mistaken as lifestyle changes occurring with age. A high index of suspicion should be followed by an estimation of serum testosterone levels; usually total serum testosterone levels are assessed. However, in select cases, free testosterone levels SHBG, FSH, LH and testosterone to oestrogen ratio are also done.

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Treatment

Testosterone replacement therapy is generally safe in ageing men and may improve libido, cognition, bone mineral density, body mass composition, and serum lipoproteins. Although contraindicated in men with prostate or breast cancer, testosterone replacement therapy in ageing men warrants examination. Any of the available testosterone formulations can be used, but injectable forms have certain advantages, including excellent dose adjustability, lack of skin irritation, and low cost. [4]

Studies of testosterone therapy in hypogonadal elderly men have shown beneficial effects on bone density (thus indirectly preventing fractures in the elderly), body composition, and muscle strength without any substantial adverse effects on lipids and the prostate. [4]

There are two different types of preparations of testosterone available:

1. Injectable: The injectable testosterone is usually given intramuscularly every two weeks.

• Testosterone cypionate (Depo-Testosterone Cypionate)
• Testosterone enanthate (Delatestryl)

2. Oral: The oral testosterone (testosterone undecanoate) is taken daily in the doses prescribed. Adequate dosing restores plasma testosterone levels within the normal range. For optimal absorption, these must be taken with food.

• Testosterone undecanoate

3. Buccal testosterone: The most recent introduction to the management is buccal testosterone which has to be used twice daily. The studies have found it to be very physiological.

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Contraindications

Absolute contraindication: Prostate cancer remains an absolute contraindication to androgen therapy. Hence, before prescribing, one should take a detailed history, do a digital examination, an ultrasound of the abdomen and PSA estimation.

Relative contraindications: One should carefully consider serious liver diseases, heart or blood vessel disease, oedema (swelling of face, hands, feet, or lower legs), kidney disease, diabetes mellitus and even enlargement of the prostate.

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Adverse effects of androgen replacement therapy

One should remain watchful about the adverse effects of androgen therapy in the form of polycythemia and sleep apnea. These adverse effects can be deleterious in men with compromised cardiac reserve.

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Disclaimer- The views and opinions expressed in this article are those of the author's and do not necessarily reflect the official policy or position of M3 India.

The author Dr. O. P. Sharma is a Senior Consultant Geriatric Medicine at Indraprastha Apollo Hospitals, New Delhi