Male hormone deficiency is a condition where the body lacks testosterone, which occurs in males aged 45 and older. Most individuals may not be aware that they are experiencing low testosterone levels and may overlook it until it reaches a point where treatment becomes challenging.

Male hormone deficiency in older men comprises both clear and ambiguous symptoms. Inaccuracy in measuring testosterone levels and concerns about the adverse effects of Hormone Replacement Therapy (HRT) have been observed. This debate stems from studies on estrogen replacement therapy in postmenopausal women, raising questions about the validity of these norms, as well as the benefits and drawbacks of using male hormone replacement therapy.

In recent decades, there have been various medical society guidelines for diagnosing and treating male hormone deficiency. These guidelines often include both age-related male hormone deficiency in older men and cases arising from common causes.

Testosterone, a male hormone, is controlled by hypothalamic pituitary gonadal (HPG) axis, consisting of hypothalamus that releases gonadotropin releasing hormone (GnRH) to anterior pituitary to stimulate the release of gonadotropin (Luteinizing Hormone [LH] and follicle stimulating hormone [FSH]). LH stimulates testosterone formation from Leydig cells of testis whereas FSH controls the function of Sertoli cells to function as spermatogenesis and to form substances, e.g., Androgen Binding Protein (ABP), Mullerian Inhibitory Substance (MIS), and
Inhibin.

Testosterone is basically formed since the age of 6-8 weeks inside womb. It reaches the maximum level at the age of 11-14 weeks. Then, it will reduce at birth. Later, it increases to high levels again during their puberty, reaches the maximum level at the age of 30 years (approx.), and reduces when getting older. The normal levels of T-hormone in adults are between 300 – 1000 ng/dL. It reaches the maximum level in the morning and down to minimum in the evening (Circadian Rhythm), which are different by 30%. In summer, the levels of this hormone are slightly higher than other seasons.

Testosterone in blood mostly adheres to sex hormone binding globulin (SHBG). The rest adheres to albumin and cortisol binding globulin (CBG). Then, it will remain as free testosterone (FT) around 1-2%, which is believed to be biologically active. It adheres to the receptor (Androgen Receptor [AR]) spreading all over the body. The word “bioavailable testosterone (BT)” refers to the hormone in the form of FT combined with testosterone adhering to albumin, because adhesion to albumin is quite loose and can simply fall out into FT form. Some experts believe that it can be active apart from FT.

1. Dihydrotestosterone (DHT): It mostly changes from testosterone by 5alpha-reductive at peripheral tissues. Only 20% of it is directly released from testis.
2. Androstenedione (A4): Most is released from testis and adrenal cortex. Approx. 15% changes from DHEA and testosterone. It reaches the maximum level in the morning.
3. Dehydroepiandrosterone sulfate (DHEAS): Almost all of it is released from adrenal cortex. It is regarded as the male hormone with the highest amount in blood but low activity. Its levels are usually stable all day.
4. Dehydroepiandrosterone (DHEA): It changes from DHEAS. Only 10-20% is released from testis and adrenal cortex. It reaches the maximum level in the morning.
5. Male estrogens (E): It mostly changes from testosterone and A4 at muscles and fat tissues. Only 20% is released from testis. It controls LH release and the function of epiphyseal plate as well as bones.

1. Sexual development in men since the age of 6 – 12 weeks in womb generates male sexual differentiation, sexual organ development, and stepping to secondary sex characteristics of puberty and adulthood.
2. Spermatosis process.
3. Emotional and intellectual changes, i.e., initiatives, aggression, and sexual desire.
4. Muscle changes: Testosterone increases muscle strength and volume.
5. Effects on bones through DHT and E that stimulate the function of osteoclast, causing higher bone mineral density. Besides, testosterone also affects sebaceous gland because it forms larger amounts of fats, acne, and erythropoiesis by stimulating bone marrow and kidneys.

นอกจากนี้ยังมีผลต่อ sebaceous gland สร้างไขมันที่ผิวหนังมากขึ้น เกิดสิว ผลต่อการสร้างเม็ดเลือดแดง (erythropoiesis) โดยกระตุ้นที่ไขกระดูกและไต เป็นต้น

1.  Lower masculinity, assessed by sexual desire (Loss of Libido), sexual potency (Erectile quality/frequency), and amounts of hair on the body. In case these disorders occur in teenage, they will cause delayed puberty.
2. Infertility.
3. Lower bone mass (osteopenia/osteoporosis), along with lower muscle strength, causing a risk of fall and fracture. Low T is a key cause of male osteoporosis despite no direct studies on the relationship between the two conditions. It is believed that 50% and 20% of men with hip as well as spinal fractures are caused by low T.
4. Emotional changes, i.e., depressive mood, irritability, and poor concentration.
5. Memory and neural function, because patients with low T will embrace lower abilities of visual memory, verbal memory, visuopatial function, and visuomotor scanning.
6. Metabolic syndrome due to larger amounts of fats, with higher risks of metabolic syndrome, Type 2 diabetes mellitus (T2DM), and cardiovascular disease (CVD). Testosterone levels will vary with internal carotid artery thickness. It also causes the risks of CVD, i.e., cholesterol levels, low-density lipoprotein (LDL) fibrinogen, and plasminogen activator inhibitor Type-1 (PAI-1).
7. Sleep disturbance.
8. Lower work efficiency and quality of life, i.e., diminished motivation, fatigue, and decreased energy.

It refers to physical and emotional changes due to lower male hormones when getting older. The word “andropause” is used for comparing with menopause in women. The difference is that ovary stops functioning immediately under menopause due to ovarian failure whereas testis can still function under andropause but with gradually lower efficiency.

Testosterone reaches its maximum level between the age of 20-29 years. And at the age of ≥ 40 years, it reduces by approx. 1-2% or 3.2-3.5 ng/dL per year. According to a study on epidemiology, it was found that the prevalence of andropause at the age of ≥ 45 years was between 12-38%, approx. 1/3 in men aged > 60 years, approx. 50% in men aged > 70 years, and would be higher in T2DM and when getting older.

1. For androgen replacement therapy (ART), male contraception, and androgen replacement therapy for postmenopausal women.
2. For treatment in non-low T patients (Pharmacological androgen therapy [PAT]), which relies on the effects of testosterone on the body. It is currently regarded as an adjunctive therapy to the standard treatment as follows.
   2.1. Anemia caused by aplastic anemia or renal failure.
   2.2. To strengthen muscles for patients with respiratory problems or heart failure, patients with autoimmune diseases
   using steroids, and AIDS patients with wasting syndromes.
   2.3. To prevent recurrence of hereditary angioedema or urticaria.
   2.4. To provide palliative care for patients with terminal breast cancer.
3. To increase rehabilitation efficiency in patients with catabolic conditions, i.e., burn, critical illness, or major surgery.

1. Prostate cancer: There have been no evidences so far that testosterone either causes prostate cancer or can stimulate metastasis in patients with this cancer.
2. Benign prostatic hyperplasia (BPH): It has been found that testosterone can increase higher PSA levels but will not exceed the normal value. However, patients with urinary obstruction due to BPH may undergo worse symptoms of BPH.
3. Hyperchromia: Hct will increase by 2-5%, particularly in older adults and those receiving testosterone injections.
4. Snoring: It is believe that testosterone acquired will worsen snoring symptoms.
5. Gynecomastia: It is caused by testosterone turning into estrogens. To solve this problem, dosage must be adjusted. It can also stimulate breast cancer.
6. Testicular atrophy and impotence: According to a study on male contraceptive drugs, the number of sperms would reduce from Week 10-11. But then, it will be back to normal 6-18 months after withdrawal. The male hormone would be formed.
7. Acne, oily skin, and alopecia.

Moreover, there were some reports of emotional disorders, e.g., psychotic symptoms, excessive libido, aggression, physical/psychological dependence, and withdrawal symptoms. Patients with renal or heart diseases would be found with edema.