ภาวะพร่องฮอร์โมนเพศชาย ฮอร์โมนเพศชายต่ำ ฮอร์โมนผู้ชาย

Understanding male hormone deficiency, low testosterone levels: What men need to know!

What is Testosterone deficiency?

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.

ภาวะพร่องฮอร์โมนเพศชาย ฮอร์โมนเพศชายต่ำ ฮอร์โมนผู้ชาย

Changes of a male hormone (Testosterone) with age

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

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.

Other types of androgens are as follows.

  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.
เทสโทสเตอโรน ฮอร์โมนผู้ชาย สร้างฮอร์โมนเพศชาย

The functions of testosterone

  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

Thus, clinical disorders due to lack of testosterone (low T) are as follows.

  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.
ภาวะพร่องฮอร์โมนเพศชาย ฮอร์โมนเพศชายต่ำ สูงอายุ

Andropause in older men

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.

There are 3 types of hormone formation and injection as follows.

  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.

Side effects of testosterone injections

  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.

Hormone replacement therapy (HRT)

  1. Effects on sexual potency: It can increase sexual potency in all aspects, but not much. It is 100% effective for those with andropause, very low testosterone, and young ages. But the results revealed that it was not much effective in older adults aged > 50 years. The result of HRT to those with normal testosterone levels (Treatment group) was not different from the control
    group. Thus, patients with low testosterone and andropause, and impotent older adults, HRT can be considered after ineffectiveness due to phosphodiesterase inhibitors.
  2. Effects on bones: It was found that HRT could increase BMD, particularly for those with andropause, very low testosterone, or who received steroids. However, there have been no studies proving that HRT can reduce fracture. Thus, groups with a high risk of fracture can add drugs with a property to prevent fracture, along with HRT. These groups of patients should also use
    drugs associated with androgens that can turn into estrogens.
  3. Effects on CVD: The results revealed effective HRT in young – middle aged patients with low testosterone. However, it could not be concluded in older adults or the group with a risk of CVD. Although HRT can reduce risk factors, e.g., effects on fats, body shape, and metabolic syndrome, there have been no supporting data for clinical outcomes/results, e.g., measurement by brachial flow-mediated dilation or the incidence of CVD. Also, it is believed that the patterns of HRT used generate different outcomes/results.
  4. Effects on body shape: It helps reduce fats and increase muscles within the first 1-2 months, particularly work efficiency.
  5. Effects on brain function, emotions, and quality of life: No studies have revealed apparent benefits yet.
ภาวะพร่องฮอร์โมนเพศชาย โรคหลอดเลือดหัวใจ

The relationship between andropause and CVD

There are the results that were both for and against the relationship of the two conditions. It was found that patients with andropause and low testosterone were related to higher mortality, both all-cause and CVD death. Lower testosterone
by 62.82 ng/dL would increase a risk of death (all-cause mortality) approx. 35%, and also a risk of death due to CVD approx. 25%. And when studying the relationship of death in patients with diabetes or renal diseases, patients with low testosterone as a comorbidity had higher mortality than the control group.

The relationship between low testosterone and CVD

According to the results of 10 meta-analysis studies that assessed the relationship between testosterone levels and CVD, it was found that men with normal testosterone levels had a lower risk of CVD than those with low testosterone.
This relationship was apparently seen in patients aged > 70 years. In contrast, mendelian randomization analysis did not support such relationship because this type of studies believed that it might be disturbed by other factors.

The conclusions of andropause and low testosterone

In conclusion, accepted and useful HRT are usually for patients with low testosterone due to apparent causes or under young ages. For older men, despite the revealed relationship between low testosterone and several disorders,
there have been no studies revealing apparent benefits, particularly for reducing mortality and CVD. Thus, this case should be appropriately considered for each individual patient.