Andropause

What is a Andropause?

Andropause, also known as late-onset hypogonadism, is a usual condition whose frequency rises with age. The presence of signs of testosterone deficiency, particularly sexual symptoms including loss of libido, morning urethral erection, and erectile dysfunction, as well as evidence of low testosterone levels, are used to diagnose late-onset hypogonadism.

Although adequate therapy options are available, mixed clinical trial findings call for more research into the complex connection between androgen insufficiency and aging. The benefits and risks of therapy should be shared with patients before beginning, and in the event of a poor response, alternate causes should be looked into.

Introduction of Andropause

Andropause is described as a syndrome linked to a fall in sexual satisfaction or a decline in a feeling of overall well-being with low levels of testosterone in older men. “Andras” represents the human male and “pause” suggests a cessation. characterized by anxiety, reduced libido and potency, irritability, fatigue, sadness, memory issues, disturbed sleep, and hot flashes. The term “hypogonadism” refers to a clinical syndrome brought on by androgen shortage, which may negatively impact the operation of numerous organs and general well-being.

Andropause is characterized by a silent onset and slow progression, in contrast to menopause, which is a universal, well-described timed process linked to complete gonadal failure. This process has been referred to by several names, including male menopause, and androgen decline in the aging male age, late onset of hypogonadism. Only men who have lost the ability to produce testes due to illnesses or accidents or those with severe prostate cancer who have had surgical or medicinal castration experience true andropause.

Age-related declines in testosterone levels occur at a rate of 1% per year, and changes in sex hormone-binding globulin (SHBG) make this reduction more prominent in free testosterone levels. The rate at which testosterone levels fall varies from person to person and is affected by chronic diseases, including obesity, illness, severe emotional stress, and drugs; this reduction can be slowed down by managing lifestyle and health-related factors. One possibly changeable risk factor for low testosterone and clinical androgen insufficiency amongst obesity parameters is waist circumference.

There is subject-to-subject variability in the testosterone threshold at which symptoms become obvious and many men with low testosterone levels lack symptoms. Age-related declines in body function ( including weakness, being overweight, osteopenia, cognitive impairment, and erectile dysfunction might be influenced by decreasing testosterone and further anabolic substances in men starting in their mid-age-30s, and testosterone deficiency in older men has been linked to an elevated risk of death beyond the subsequent 20 years

one of two approaches for andropause: a clinical one-symptom questionnaire like Androgen Deficiency in the Aged Male or a statistical one under the 2.5th percentile of testosterone adult level. However, the issue is made worse by the fact that many of the symptoms experienced by men with low testosterone levels are low and might not be clinically significant

Occurrences of Andropause

Andropause, a clinical and biochemical condition, is a common disorder that is commonly underdiagnosed and frequently goes untreated. Men aged 30-69 reported having a 3.1–7.0 percentage of occurrence of andropause, whereas those older than 70 reported having an 18.4 percent occurrence. Men aged 30-79 reported having a 5.6% occurrence of symptomatic androgen deficiency, which rises significantly with age. the incidence of low testosterone and the presence of three sexual symptoms was two percent. Additionally, approximately 5 to 35 percent of hypogonadal guys are believed to really receive treatment for their illness.

Causes of Andropause

In males who may be experiencing andropause, the decline in testosterone plays a significant role. However, as men age, their bodies begin to produce less testosterone, and sex hormone binding globulin (SHBG), a hormone that removes useful testosterone from the blood, begins to develop in their bodies as well. Some of the accessible testosterone that is circulating in the circulation is bound by sex hormone-binding globulin. substance testosterone, which is accessible for utilization by the body, is the testosterone that is not linked to the sex hormone binding globulin hormone.

The blood levels of the substance testosterone are reduced in men who experience andropause-related symptoms. Because of this, the body’s tissues that are activated by testosterone receive less of it, which could result in a variety of physical and possibly mental problems like tiredness, mood swings, reduced testosterone levels, small estradiol concentrations, low growth hormone and not sufficient calcium intake, vitamin D deficiency, poor nutrition, and the consumption of drugs like glucocorticoids or anticonvulsants, Lack of exercise or inactivity brought on by weakness or immobility due to severe osteoarthritis, lifestyle factors such as excessive alcohol consumption or smoking age-related illnesses such as primary and secondary hyperparathyroidism, and multiple myeloma, genetic predisposition, and/or low peak bone mass during adolescence or early adulthood as a result of a prolonged illness or delayed puberty decreased bone mass, unusual bone fracture and structure may all contribute to the age-related decline in bone mineral density and abnormalities in the structure of bones..

Symptoms of Andropause

Common symptoms of males going through andropause include the following, though individual symptoms may vary:

• Low sexual motivation challenges getting a hardy penis or having erections that are less than normal fatigue depression
• Angry and moody behavior
• loss of muscle mass or strength height loss
• hot flashes or perspiration, increased body fat, or breast discomfort or swelling

Physiology of Andropause

Serum T Levels Decline with Age

At a rate of around 1% per year, aging is linked to a constant and progressive fall in serum T levels starting in the third decade. Because of this, the serum total T levels of twenty percent of men over 60 and fifty percent of men over 80 are below the range considered normal for young men.

About ninety-eight percent of the circulating testosterone in the blood is attached to serum proteins, mostly to albumin and sex hormone-binding globulin, which is the main binding protein for testosterone in the blood. serum t in circulation is only partially loose or free, ranging from 1% to 2%. T is securely attached to sex hormone-binding globulin with a high connection, which prevents most tissues from acting on sex hormone-binding globulin-bound serum T, on the other hand, serum T, binds to albumin with little attraction (weakly), making both albumin-bound and free testosterone accessible to the majority of tissues for activity. Serum-free T and accessible T (free plus albumin-bound T) concentrations fall far faster than total T levels with aging because the concentration of sex hormone-binding globulin rises with age. Therefore, the amounts of these physiologically active components are significantly greater in older males.

Changes in sex hormone binding globulin caused by aging and other factors have significant clinical results for the diagnosis of androgen insufficiency. Total serum T levels fluctuate in the same manner as changes in sex hormone-binding globulin and/or albumin because total serum T analyses detect both free serum T and serum T bound to sex hormone-binding globulin and albumin. Changes in sex hormone-binding globulin should not impact measurements of free or available T. As a result, sex hormone-binding globulin offers a better evaluation of physiologically active T in blood, particularly in frequent clinical conditions like aging, which causes an increase in sex hormone-binding globulin, or moderate obesity, which causes a drop in sex hormone-binding globulin.

Many older men with low-normal total testosterone levels also have free or accessible testosterone levels that are below the range considered normal for young men because sex hormone-binding globulin levels rise with age. Therefore, it is advised to test accessible or free Testosterone utilizing equilibrium dialysis or ammonium sulfate precipitation, respectively, or to calculate it from total Testosterone and sex hormone binding globulin values to identify androgen insufficiency in older men. Most regional labs use a solid-phase direct analog immunoassay kit to test free testosterone.

The values gained differ significantly from those received by equilibrium dialysis or calculated from sex hormone-binding globulin and directly change with changes in sex hormone-binding globulin levels, even though free Testosterone analysis utilizing this method matches with those utilizing equilibrium dialysis. As a result, free testosterone measurements made with direct analog immunoassay kits might not offer any further clinically relevant information.

They frequently overdiagnose androgen deficit in men with low sex hormone-binding globulin(SHBG) levels, such as individuals who are somewhat obese, while underdiagnosing androgen deficiency in older men. It is not recommended to utilize direct analog immunoassays to test free Testosterone levels in individuals who may have changed SHBG levels, such as older males.

Age-Related Decline in Hypothalamic gonadotropin-releasing hormone (GnRH) Regulation and Testis Function

Age-related decreases in blood testosterone levels are caused by both decreased testicular T production and decreased hypothalamic gonadotropin-releasing hormone (GnRH) secretion, which in turn leads to insufficient stimulation of luteinizing hormone (LH) secretion by the pituitary gland.

In older men, there is a reduction in basal testosterone production, a reduction in the number of Leydig cells, the cells of the testis that generate testosterone, and a significant reduction in T secretion by the testis in response to maximal stimulation by human chorionic gonadotropin (hCG), an luteinizing (LH)-like hormone. The reduction in metabolic clearance of testosterone that also happens with aging lessens the effect of lower testosterone generation on circulating T levels. In healthy older men compared to young men, the usual diurnal variation in serum T levels with the highest levels in the morning is reduced, suggesting a change in the hypothalamus rhythmic pacemaker activity. Because the typical diurnal variation in T levels is decreased with aging, serum in the morning The levels of testosterone are lower in elderly males compared to young men, while late afternoon values are more comparable.

Aging also causes a reduction in the seminiferous tubule segment of the testis. Histologically measured spermatogenesis is lower in older men compared to younger men although sperm concentration in the discharge of the semen fluid is either unchanged or higher due to decreased discharge of the semen volume and frequency. Although there are fewer sperm with typical forms and movement, older men tend to have reasonably good in vitro fertilization capacity. Overall fertility rates decline with age, mostly because of decreased sexual activity, despite generally well-preserved fertility capacity and reported cases of paternity in males older than 90 years.

The risk of inherited autosomal chief disorders in children rises with more extended parent age. With age, spermatogenesis-supporting Sertoli cells, also known as seminiferous tubule cells, and serum levels of inhibin B, a Sertoli cell peptide product, all decline. The inhibitor B is a feedback inhibitor of follicle-stimulating hormone (FSH) secretion from the pituitary gland. The majority of the drop in inhibin B levels seems to start around middle age, with concentrations remaining consistent through old age.

A progressive rise in serum gonadotropin, follicle-stimulating hormone (FSH), and to a lesser extent, luteinizing hormone (LH)concentrations is linked to a reduction in serum T levels with aging. Although gonadotropin levels rise with age, for younger men they frequently stay within the broad range of normal. Low serum T and normal gonadotropin levels suggest concurrent hypothalamic-pituitary dysfunction along with primary testicular failure in aged men, according to the ensuing hormonal pattern. During the workup of older men with symptoms of androgen shortage, low serum Testosterone and normal gonadotropin levels, compatible with secondary hypogonadism, are often identified.

age-related changes in pulsatile GnRH secretion from the hypothalamus is provided by pulsatile gonadotropin secretion. Young hypogonadal men with low blood T levels show an increase in Luteinizing hormone pulse frequency and amplitude correlated with reduced T negative feedback when compared to normal men. Healthy older men with low serum T levels exhibit abnormal Luteinizing hormone pulse frequency, lower Luteinizing hormone pulse amplitude, and more Luteinizing hormone disordered production compared to young men, suggesting that the hypothalamic GnRH pulse generator is impaired with age. Although the systematic secretion of follicle-stimulating hormone (FSH) is maintained in elderly men as compared to young men, basal FSH secretion and pulse amplitude both rise.

Age-related changes in the central nervous system’s (CNS) endogenous opiate substance control of GnRH production by the fact that older men have a diminished stimulation of gonadotropin secretion generated by naltrexone or naloxone, opioid receptor antagonists. In elderly men compared to young men, gonadotropin inhibition is more sensitive to T-negative feedback and less responsive to the lack of androgen brought on by an androgen receptor antagonist (flutamide) or an androgen synthesis inhibitor (ketoconazole).

Older men show somewhat reduced gonadotropin responsiveness to acute GnRH but a normal LH response to chronic pulse-like GnRH treatment as compared to young men, showing that pituitary gonadotropin output is unaffected by aging. All of these results point to a relationship between aging and dysfunctions of the testis and the hypothalamus GnRH that controls gonadotropin secretion.

Age-related Alterations in Androgen Action and Active T-cell Metabolism

Older men have lower levels of androgen receptor gene expression in the CA1 area of the hippocampus and fewer androgen receptor binding sites in their genital skin. In elderly men without benign prostatic hyperplasia (BPH), androgen receptor expression and nuclear androgen receptor levels in the prostate remain unchanged and comparable to young men. In contrast to young men, older men with benign prostatic hyperplasia (BPH) have lower prostate androgen receptor expression and higher nuclear androgen receptor levels.

A shorter cytosine–adenine––guanine (CAG) repeat length is linked to higher androgen receptor activity and probably higher overall androgen action. The length of trinucleotide CAG repeats in the androgen receptor gene is varied and is connected with changes in the activity of transcription. The Cytosine–adenine–guanine (CAG) repeat length in the androgen receptor gene was found to be correlated with blood total and free T levels. An androgen receptor genotype with a shorter CAG repeat length was found in older males with lower serum T levels, indicating overall higher androgen activity. In older men with shorter CAG repeat length, it is thought that raised androgen action at the level of the hypothalamic-pituitary axis may lead to greater feedback suppression of gonadotropin and, consequently, endogenous androgenic testosterone production.

Androgen action involves a complex interaction between androgen ligands like testosterone, the androgen receptor, tissue-specific coactivators, and corepressors with androgen-response elements in particular genes. It is not just a function of androgen receptor expression in target tissues and Cytosine–adenine–guanine (CAG) repeat length. these two transcription factors, along with others, change with age in tissues that are androgen targets. however, indicated that, in addition to circulating T levels, age-associated variations in androgen action may play significant roles in the alterations of physiological function that happen with normal aging as well as in the mechanism of age-related diseases.

T is actively metabolized to 5 alpha-dihydrotestosterone (DHT), a more potent androgen than T, by the enzymes 5 alpha-reductase type 1 and 2, which are primarily found in skin and the prostate, and to the potent estrogen, estradiol (E2), by the enzyme aromatase, which is situated primarily in adipose tissue. Many of testosterone’s effects are at least partially judged by its active metabolites, estradiol found in the bone, brain, and lipids) and alpha-dihydrotestosterone (DHT) is found in the prostate. Serum total estradiol and DHT levels should not alter or change very little with aging, despite lowering Testosterone levels.

This shows that there is a relative increase in the chemical reaction of Testosterone to estradiol perhaps because of an increase in adipose tissue bulk and a relative decrease in the metabolic clearance of testosterone to alpha dihydrotestosterone and estradiol. Serum-accessible or free estradiol and dihydrotestosterone levels would be assumed to reduce with aging because serum Sex hormone-binding globulin levels rise with age. accessible estradiol levels decrease with aging and connect with male bone mineral density more favorably than testosterone.

Age-related changes in serum levels of peripheral androgen activity, such as 3 alpha-, 17 beta-androstanediol glucuronide (3 alpha-diol G), show a drop in the total amount of circulating androgen. As people age, the tissue concentrations of dihydrotestosterone in the epithelial compartment of the prostate gland and estradiol in the endothelial compartment rise, highlighting the significance of active testosterone metabolism in androgen target organs and within particular parts of these organs.

Age-Related Comorbid Conditions and Drugs Reduce Serum T Levels

Age-related comorbid illnesses such as chronic renal, liver, or pulmonary disease, malignancy, and the use of specific medications that are frequently utilized for the treatment of these illnesses e.g., glucocorticoids and CNS-active medications as well as malnutrition that is frequently linked to illness all contribute to the decline in serum testosterone levels linked to healthy aging. Older men with serious illnesses, such as cancer or stroke, as well as those in an inpatient rehabilitation center or nursing home, have significantly lower serum testosterone levels than older men who live in the community and are healthy. Additionally, the number of testosterone levels below the range considered normal for either healthy young 60 to 90 percent or older men 20 to 30 percent is higher in these sicker older men.

Physiological Changes Associated With Aging That Are Constant With Androgen Deficiency

Numerous changes in physiological processes are brought on by aging, many of which are controlled by androgens. Lower muscle strength and power lowered muscle mass, lowered physical function, lowered aerobic capacity, greater risk of falls and loss of independence, improved body fat during middle to old age, particularly greater quantities of visceral adiposity, which is linked to insulin resistance, are all physiological changes linked with the age-related reduction in serum testosterone levels. reduced power, energy, and general well-being; anxiety and depression; reduced sexual function reduced sexual desire, sexual activity, and erectile function, impaired concentration and cognitive function; sleep disturbances and poor sleep quality; and lowered hematopoiesis.

Younger hypogonadal men with androgen deficiency and testosterone replacement therapy experience similar changes in physiological function, including a gain in skeletal muscle mass, and strength, a decrease in body fat mass, an improvement in energy, well-being, mood, an increase in erections that occur on their own during sleep an improvement in sexual function, and an increase in erythropoiesis and hematocrit. Therefore, it is expected that, at least in part,

Levels of testosterone are positively correlated with poor body mass, muscle mass, and strength in older men, whereas these relationships are not present in younger men. Additionally, testosterone is negatively correlated with total or abdominal fat mass, suggesting a link between serum testosterone and age-related changes in the structure of the body and muscle strength. males with type 2 diabetes mellitus have lower serum T levels, and low T levels are linked to an increased risk of acquiring type 2 diabetes. The use of total or free T-tests that were influenced by sex hormone binding globulin concentrations, which are considerably lower in obese men.

an inverse relationship between testosterone concentrations and hypertension, insulin and glucose levels and prothrombotic factors, atherosclerotic vascular disease, and the presence or severity of coronary artery disease (CAD), as well as a positive relationship between free T levels within the physiological range and high-density lipoprotein (HDL) cholesterol levels. testosterone levels and the occurrence of coronary artery disease. Testosterone and cardiovascular mortality are not related. Therefore, a beneficial or neutral effect of Testosterone on heart disease risk rather than a harmful effect.

The age-related decrease in accessible estradiol levels may be a greater indicator of bone loss with aging in males than testosterone levels, as there is a higher link between accessible estradiol levels and bone mineral density and fracture risk rather than between testosterone and these results. the critical role of estradiol in selecting and maintaining healthy bone mass can be found in the results of severe osteoporosis in men with estrogen resistance or deficiency brought on by changes in the estrogen receptor or chemical substances, respectively. An aromatase(chemical reaction) inhibitor raises the markers of bone resorption in older men, while estradiol replacement in men reduces the markers of bone resorption. suggesting that testosterone-to-estradiol (E2) conversion has a significant role in the prevention of bone resorption. Men with androgen resistance brought on by changes in the androgen receptor gene, however, have lower BMD, which suggests that androgens are also crucial for the growth and maintenance of men’s bone mineral density.

older men with T and E2 insufficiency caused by a GnRH agonist with an aromatase inhibitor were treated with either physiological testosterone or estradiol replacement to determine the precise functions of T and E2 in controlling bone turnover. While both T and E2 were discovered to be crucial for preserving bone production, E2 was revealed to be dominant in preventing bone resorption. Because T undergoes a chemical reaction to produce E2, The decrease in serum E2 levels with aging is probably due, at least in part, to the loss in its T. Last but not least, hip fractures in older men are a risk factor for lower testosterone levels.

Major correlations between T levels and many elements of brain function are also discovered. An inverse relationship between accessible T and depression score was also discovered, pointing to T’s potential function in the control of mood. maintain sexual interest and desire, relatively low serum T levels are necessary. Even though androgen shortage may worsen sexual dysfunction, it rarely stands alone as a significant factor in older men’s erectile dysfunction. Most frequently, vascular disease, neuropathy, and medicines are responsible for erectile dysfunction. Testosterone levels have an inverse relationship with markers of psychosocial stress and are connected with sleep efficiency and relaxation. The maintenance of cognition and memory may depend significantly on T, as evidenced by the link between accessible T and general or spatial cognitive function

Age-Related Physiological Changes with Multifactorial Etiologies

It would be thoughtless to think that the only age factor is responsible for androgen deficiency The majority of age-related changes in physiological function have a complex cause, as many geriatric diseases and many physiological causes are modifiable or curable. Therefore, comprehensive consideration of all-cause factors is necessary for effective therapeutic therapy of these changes.

the necessity for geriatricians and gerontologists to view aging as beginning at birth and continuing throughout a person’s lifetime, rather than basically from early adulthood to old age. it is critical to realize the crucial role that falls and trauma play in the principal clinical results of decreased bone mass, unusual bone structure, and fracture, which may result in pain, deformity, and need for surgery and related complications like pneumonia, deconditioning, loss of function, independent living, The clinical complexity is increased due to interactions between the various factors that may be responsible for age-related physiological damage, which highlights the value of managing older patients utilizing a multifactorial approach.

serum level T levels may be linked to decreased exercise or inactivity due to weakness and/or lack of motivation, as well as an increased risk of falling due to weakened muscles and unstable balance. By boosting E2, GH, and IGF-1 levels and physical activity, T therapy may indirectly increase BMD while decreasing the risk of falls through improving body strength Multiple components that lower BMD The decrease in blood levels of testosterone may also be influenced by inadequate nutrition, drugs, other medical conditions, and excessive alcohol consumption. correction of inadequate nutrition, stopping the use of specific drugs, treatment of illnesses, and discontinuation of alcohol abuse may increase serum T levels and remove the need for T treatment.

Diagnosis

Currently, a number of symptoms and indicators that point to a low testosterone level are necessary for the diagnosis of andropause which has already been mentioned

it is important to rule out conditions including depression, hypothyroidism, persistent drinking, and the use of drugs like corticosteroids, cimetidine, spironolactone, digoxin, opioid analgesics, antidepressants, and antifungal agents, acute illness should not be included before creating a diagnosis of andropause

The basic requirements for the diagnosis of andropause in aged men include the presence of three sexual symptoms reduced libido, morning erections, and erectile dysfunction, along with total testosterone levels of less than 11 nmol/l and free testosterone levels of less than 220 pmol/l.

Because of their low specificity 30 and 39%, respectively questionnaires like the Aging Male Symptom (AMS) Score and ADAM are not advised for the diagnosis of andropause.

Laboratory diagnosis

the testosterone levels alter particularly as an outcome of circadian and circannual rhythms, episodic secretion, and measurement divergences. In the presence of symptoms, a sample for total testosterone determination should be obtained between 0700 and 1100 h.
the total testosterone attention describes the sum of unbound and protein-bound testosterone in circulation. Most of the circulating testosterone is attached to sex hormone binding globulin and to albumin; only 0.5 to 3 percent of circulating testosterone is unattached or “unrestricted.” The term “bioavailable testosterone” refers to unattached testosterone plus testosterone bound gently to albumin; this term recalls the idea that in addition to the unbound testosterone, albumin-bound testosterone is simply dissociable and thus bioavailable.

Total testosterone concentrations are also affected by changes in sex hormone binding globulin (SHBG) levels, so it’s critical to confirm low testosterone levels in men with start testosterone levels in the slightly hypogonadal range. This is because thirty percent of these men may reconsider having normal testosterone levels, and fifteen percent of young, healthy men may do so in a 24-hour period.

When total testosterone levels are close to the lower limit of the normal range and when altered sex hormone binding globulin levels are supposed, such as reduced sex hormone binding globulin (SHBG) in moderate obesity, diabetes mellitus, chronic illness, use of glucocorticoids, hypothyroidism, or raised sex hormone binding globulin in aging, hepatic cirrhosis, hepatitis, hyperthyroidism, use of estrogens, and HIV disease, free or unbound testosterone levels should be measured.

The lower limit of the normal range for healthy young men determined in their laboratory should be used by professionals. The average testosterone threshold for the majority of symptoms was found to be around 300 nanogram/deciliter (10.4 nmol/l), which is the lower limit of the normal range for young men. Below this threshold, symptoms were more likely to occur rather than those above 300 nanograms/deciliter.

Professional organizations generally agree that the replacement is not necessary when the total testosterone level is above 12 nmol/l (350 ng/dl). Similar to this, it is widely agreed that patients with blood total testosterone levels below 8 230 nanogram/deciliter will typically benefit from testosterone therapy. When the serum total testosterone concentration is between 230 and 350 nanogram/deciliter, do it, again and again, the measurement of total testosterone with sex hormone binding globulin to estimate the free testosterone or unbound testosterone must advantage the patient

The detection of testosterone using immunometric techniques nowadays can differentiate between individuals with hypogonadism and healthy adult males. The most reliable method for measuring free testosterone and unbound testosterone is equilibrium dialysis and sulfate precipitation. Computed values are preferable since none of the most reliable procedures are typically available. Estimated free testosterone and free testosterone determined by equilibrium dialysis correlate significantly. The threshold levels for unbound testosterone are method-dependent and only sometimes known. Salivary testosterone has also been proven to be a reliable alternative to free testosterone measurements. but cannot currently be advised for widespread usage due to the lack of standardization in the methodology and the absence of adult male ranges in the majority of hospitals.

The next step is to measure the serum levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) to establish whether the patient has primary or secondary andropause. While low or lower-than-normal LH and FSH levels indicate secondary andropause, raised LH and FSH levels indicate intrinsic andropause. Low testosterone along with normal LH and FSH suggests a fundamental pituitary and/or hypothalamic dysfunction. LH determination alone is sufficient until fertility is a problem. Pituitary imaging and prolactin levels are advised to check for structural abnormalities in the hypothalamus-pituitary region if the total testosterone concentration is below 150 ng/dl.

Other endocrine systems, such as estradiol, growth hormone (GH), and dehydroepiandrosterone (DHEA), also vary with age, although the importance of these changes is poorly known. Estradiol, thyroid hormones, cortisol, DHEA, DHEA-S, melatonin, growth hormone, and insulin-like growth factor-1 levels should not be measured unless other endocrine abnormalities are imagined based on the patient’s clinical signs and symptoms.

The process for identifying androgen deficiency in older men

While the percentage of men with low blood testosterone levels increases with age, a sizable portion of older men still have T levels that are within the normal range. The clinical signs of androgen shortage may be present in these people. a considerable age-related fall in T levels within the wide normal range the clinical signs of androgen insufficiency are non-specific and typically multifactorial in character. Additionally, the clinical significance of gently reduced serum T levels in the absence of androgen deficiency-confirming clinical symptoms is not clear

As a result, the diagnosis of andropause needs the confirmation of serum-free or unbound T levels that are below the range considered normal for younger men as well as the presence of clinical signs or a clinical syndrome.

Two screening tools have recently been created in order to identify older men who are at high risk for low serum T levels and to identify a clinical diagnosis linked to low T. The Androgen Deficiency Aging Male (ADAM) questionnaire, a symptom-based tool, has a sensitivity of eighty-eight percent and a specificity of sixty percent for detecting older men with low Testosterone symptoms. According to this questionnaire, symptoms of low serum T levels include decreased libido, fatigue, lack of energy, reduced power and/or endurance, loss of height, reduced enjoyment of life, feeling depressed or unhappy, weaker erections, a reduced capacity to play sports, inability to stay awake after dinner, and reduced work performance. Similar symptoms have been observed by others for elderly men with androgen insufficiency.

The MMAS questionnaire, a causes-based tool, has a 75 percent sensitivity and 50 percent specificity for identifying risk factors for low testosterone levels in older men. Age of 60 years or older, treated diabetes mellitus, treated asthma (a surrogate for glucocorticoid use), sleepiness (less than 5 hours), nonsmoking, headaches in the previous two weeks (a surrogate for stress), low dominance (dislike of a directing role), and body mass index (BMI) 27 to 30 or greater than 30 are risk factors that are linked to low total T levels. The ability to detect people with low T levels may be improved by combining symptoms and risk factors

Low serum T levels in multiple circumstances without treatable or reversible causes

An early morning T level measurement should be taken to confirm low serum T levels if clinical signs point to androgen insufficiency. A free or absorbed T level by equilibrium dialysis or ammonium sulfate, respectively, is advised for confirmation of androgen deficit in older men in order to eliminate the amazing effects of changes in SHBG levels on total T. Alternately, free or bioavailable T levels can be determined from total T and SHBG measurements; the results are similar to those obtained by ammonium sulfate precipitation and equilibrium dialysis.

Total testosterone tests and free testosterone by direct analog immunoassay are not advised since they fluctuate with changes in SHBG levels. However, the only tests now offered in nearby clinical laboratories are frequently these ones. If the direct analog immunoassay technique is first employed to assess older men with symptoms of androgen deficiency, values that are in the low-normal to moderately low range total testosterone of 350-200 nanogram/deciliter should be confirmed with a free or unbound T level measured utilizing a more precise technique. Total T levels of 200 ng/dl in the presence of consistent clinical signs are typically diagnostic of androgen deficit unless SHBG levels are extremely low in nephrotic syndrome.

Additional Analysis of Elderly Men With Low T Levels

Serum prolactin and iron levels should be measured to rule out hyperprolactinemia and hemochromatosis (iron overload), both of which may inhibit gonadotropin and Testosterone secretion if the repeated serum-free or absorbed T level is down and are related to unsuitably normal or lower gonadotropin levels a hormonal sequence of secondary hypogonadism. An MRI or CT scan of the hypothalamus and pituitary should be carried out in people with extremely low testosterone. total testosterone 150 ng/dl, low gonadotropin levels, and/or those with noticeably increased prolactin levels 100 ng/ml), in order to rule out a tumor or destructive lesion in this area.

Treatment of Andropause

Baseline Assessment and T Replacement Targets

Prior to starting T therapy, a thorough baseline clinical evaluation should be carried out to determine whether there is a previous diagnosis of prostate or breast cancer or a family record of dangers for these androgen-dependent malignancies; severe benign prostatic hyperplasia symptoms using the Berlin Questionnaire or Epworth Sleepiness Scale, or sleep apnea using the American Urological Association (AUA) Symptom Score or an abnormal digital rectal examination

Erythrocytosis (hematocrit greater than 52) or an elevated PSA level greater than 4 ng/ml after initial treatment for prostatitis and repeat prostate-specific antigen measurement are three conditions that call for prostate ultrasonography and biopsy like induration or nodule.

An acceptable goal of T replacement is to return blood T levels into the mid-normal range for younger men and to minimize the clinical signs of androgen deficit due to the dosage response effects of T treatment and the lack of proof for increased androgen requirements in older men.
Some panelists preferred treating symptomatic older men with testosterone levels below the lower limit of normal for healthy young men, which is 280–300 ng/dl, while others preferred a level under 200 ng/dl depending on the severity of clinical symptoms.

The discovery that men with results below that level frequently have symptoms that may be related to low testosterone more strongly affected the people who supported treating individuals with values greater than 300 ng/dl. The lack of testosterone effects of treatment, when patients had pretreatment values of 300 ng/dl but suggestions of beneficial effects when the pretreatment values were closer to 200 ng/dl, were more influential on the members of the panel who supported not treating unless the serum testosterone was as low as 200 ng/dl

For replacement therapy, natural testosterone preparations should be utilized. The injectable, transdermal, oral, and buccal testosterone formulations that are now on the market are secure and efficient. The treating physician should be well-versed in the pharmacokinetics, as well as the advantages and disadvantages of each treatment. A choice of trial should be a combined decision of an informed patient and physician.

Short-acting planning might be preferred over long-acting station planning in the initial treatment of patients with andropause because of the possible occurrence of a side effect during treatment specifically raised hematocrit or prostate carcinoma which requires rapid discontinuation of testosterone replacement. Testosterone replacement therapy for older men is offered in a variety of forms. Parenteral 17 beta-hydroxy-esters of Testosterone, Testosterone enanthate, or Testosterone cypionate, often delivered by intramuscular injection at a dosage of 150–200 mg every two weeks, are the most commonly utilized preparations for Testosterone replacement. These T esters are the least-priced formulation for testosterone replacement therapy that is also secure and efficient.

Nevertheless, serum T levels increase to supraphysiological levels in the early days of testosterone esters injection and then drop to the low-normal range or below normal immediately before the subsequent injection. Energy, libido, and mood swings are frequently associated with the dramatic differences in T levels between injections and may be disturbing to patients. temporarily elevated supraphysiological T levels and an increase in average Testosterone level overall while treatment with a Testosterone ester might be related to higher side effects like erythrocytosis.

Low-dose testosterone supplementation with T enanthate or cypionate dosage of 50-100 mg every two weeks may benefit libido, energy, and general well-being without these negative effects.

Surgical procedure

For T replacement therapy, there are three transdermal T patches available. They are more frequent than T ester injections in terms of physiological serum T levels (typically in the low- to mid-normal range). T patches offer the advantage that treatment can be stopped quickly if side effects manifest in older men, but they are more costly than T ester injections, which can be used in their place. Although the Testoderm patch (Alza, Palo Alto, CA) is efficient, many men find that it must be applied to clean, dry, frequently hairless areas.

However, it is unknown what high dihydrotestosterone levels will do clinically. Although the adhesive and/or boosting ingredients in the Androderm patch (Watson, Corona, CA) can be placed on skin elsewhere than the intestines, they have the potential to cause severe skin irritation. Co-application of a glucocorticoid cream, such as triamcinolone, can lessen skin irritation. Because it has less adhesive and doesn’t contain boosting agents, the Testoderm TTS patch (Alza, Palo Alto, CA) is also applied to hair skin and causes significantly less skin irritation. It may not stick to the skin as well as the Androderm patch, especially if you exercise hard or sweat excessively, which lowers serum T levels.

AndroGel (Unimed/Solvay, Buffalo Grove, IL) is a transdermal T gel that was just made accessible for Testosterone replacement therapy. Physiological serum testosterone levels are produced by daily administration of this hydroalcoholic T gel formulation. Testosterone levels in the low-, mid-, or upper-normal range can be reached with T gel dosage adjustments without significantly irritating the skin. Due to the huge surface region of skin covered, AndroGel might also result in serum dihydrotestosterone levels that are over the normal range. If the skin surface where the T gel is placed is not covered or cleansed which is acceptable 1 hour after application), transmission of T to partners or children is possible.

Because of their possible liver toxicity, 17a-alkylated androgen preparations like 17a-methyl testosterone are no longer recommended. However, oral testosterone undecanoate avoids first-pass metabolism through preferential lymphatic system absorption, making it empty of liver damage. Transdermal gels, which give 5 to 10 mg of testosterone daily, are colorless hydroalcohol gels with a testosterone concentration of 1% to 2%. The difficulties of continuing the buccal treatment have made a substance called complex testosterone preparations unpopular. Local site infection and extrusion are possible side effects of subdermal implants. The effects of intranasal testosterone must be determined by more long-term research because it is more closely related to the typical circadian variation of testosterone.

observing the patient on androgen therapy

When starting testosterone therapy, it is recommended to use any of the approved formulations, selected based on the patient’s preferences, taking into account pharmacokinetics, treatment stress, and cost, to try and attain testosterone levels in the mid-normal range. Three to six months after starting treatment, the level of testosterone should be tested.

selection of the hemoglobin should be made at baseline, every 3 to 6 months, and subsequently yearly. The therapy must be ended until the hematocrit falls to a level that is secure and can be restarted at a lower dose if it goes above 54 percent. After 1-2 years of testosterone therapy, bone mineral density in men with osteoporosis or low trauma fractures should be assessed.

It is advised to check prostate-specific antigen levels before starting treatment, then follow evidence-based recommendations for prostate cancer screening after 3-6 months. If prostate-specific antigen increases by more than 1.4 ng/ml within a 12-month period, prostate-specific antigen speed increases by more than 0.4 ng/ml/year utilizing the prostate-specific antigen level after 6 months of testosterone therapy a (PSA velocity should be used if there is longitudinal PSA data for more than 2 years, and international prostate symptom score (IPSS) increases by more than 19), then urology appointment is advised.

Evaluation of treatment results and decisions for further therapy

The signs and symptoms of low testosterone might improve throughout a variety of time periods. Treatment should be stopped if clinical symptoms do not improve within a fair amount of time 3-to 6 months are sufficient for improved body fat, libido, and sexual function; improvement in bone mineral density needs a larger period of time.

T Treatment in Older Men With Recurrently Low T Levels

A small number of short-term controlled foundations for the current understanding of the advantages and dangers of T therapy in older men. As a result, there is not enough information to create definitive, clinical suggestions and general guidelines based on evidence for Testosterone treatment in older men. At this time, routine care for older males cannot be advised. Before recommending and prescribing T therapy for older men with clinical symptoms associated with prostate cancer, individual practitioners must depend on solid medical judgment and informed preferences of patients after a full examination and discussion of the possible advantages and dangers of T therapy. with continuous low T levels and androgen deficiency

Only older men with clinical signs of androgen deficit and consistently low serum T levels, in whom treatable reasons of low T have been addressed, should be given consideration for medication. These men should begin treatment if the doctor and the patient agree that the benefits, such as severe muscle weakness, osteoporosis, or changes in sexual function or mood, balance the risks, such as erythrocytosis and prostate disease, and if there are no restrictions. Prostate and breast cancer are absolute limitations to T treatment and unchecked benign prostatic hyperplasia (BPH) with significant bladder outlet obstruction, unchecked obstructive sleep apnea syndrome, and erythrocytosis are relative limitations.

Benefits of testosterone replacement therapy

Increased strength, muscle mass, and body composition

testosterone therapy did not affect overall body weight, but instead reduced fat mass and increased muscle mass. Both in males whose baseline testosterone levels averaged less than 300 ng/dl and the average baseline was noticeably higher than 300 ng/dl, these alterations were seen. The effects of testosterone on muscle strength varied, with only leg/knee extension and the grip with the arm that is dominant indicating a tendency for improvement. Uneven results have been found regarding the effects on bodily functions, and few investigations have included males who had functional restrictions. The effects of these body composition changes on strength, muscle function, metabolic rate, and cardiovascular functions.

Bone mass and fracture frequency

Younger and older hypogonadal males have higher rates of osteopenia, osteoporosis, and fractures. When compared to healthy males, andropause men had osteoporosis twice as frequently. All ages of andropause males have an increase in bone density when testosterone is replaced. Testosterone causes this action by boosting osteoblastic activity and decreasing osteoclastic activity by chemical process into estrogen. The combined results point to a positive impact on lumber spine density and opposing findings for femoral neck bone mineral density. In particular among patients receiving long-term glucocorticoids, intramuscular testosterone trials indicated considerably higher benefits on lumber bone density than transdermal testosterone preparations.

Using testosterone for sexual activity

The International Assessment of Erectile Function questionnaire’s sexual desire, erectile, and orgasmic function categories have been found to strongly correlate with serum-free testosterone.

Patients for testosterone therapy include males with erectile dysfunction, decreased libido, and/or confirmed testosterone insufficiency. When testosterone therapy doesn’t work as planned, the underlying causes of erectile dysfunction need to be re-examined. A brief 3-month treatment trial might be warranted given the reality of a clinical picture of testosterone insufficiency and borderline serum testosterone levels. The delivery of testosterone must stop if there is no reaction. Before recommending a long-term course of treatment, it is essential to continue examination because a positive response may be placebo-developed.

testosterone and phosphodiesterase-5 inhibitors when used together to treat hypogonadal or borderline healthy functioning men. These findings still need more research because they are just preliminary. However, hypogonadal patients with erectile dysfunction who do not respond to either treatment alone should be thought about receiving a combined therapy. It is uncertain whether testosterone, phosphodiesterase-5 inhibitor (PDE-5-I), or a combination of the two should be used as the first treatment for hypogonadism and erectile dysfunction in men.

The number of nocturnal erections, sexual ideas and drive, successful intercourses, scores of erection function, and overall sexual satisfaction may all have been moderately boosted by testosterone therapy, according to a number of placebo-controlled trials. However, a more consistent impact on libido than erection function has been claimed.

Testosterone and metabolic syndrome, type 2 diabetes, and obesity

The risk factors for cardiovascular disease and metabolic syndrome are positively impacted by testosterone. Low endogenous testosterone levels are associated with mortality from all causes, including cardiovascular disease. Hypogonadal men also exhibit a number of metabolic syndrome symptoms, including obesity, hypertension, dyslipidemia, poor glucose regulation, and insulin resistance. Numerous epidemiological analyses have demonstrated a strong association between low serum testosterone levels in healthy men and obesity.

Twenty to sixty-four percent of obese men have low levels of serum total or free testosterone, and thirty to fifty percent of people with type 2 diabetes mellitus have low levels of plasma testosterone together with low levels of gonadotropins borderline and clear hypogonadism. There is no correlation between serum testosterone concentration and glycemia level. Given the high incidence of diabetes, men with diabetes who show signs of low testosterone should have their serum testosterone levels checked.

Particularly in non-overweight, middle-aged men body mass index (BMI) of 25, low total testosterone, and SHBG combined with androgen insufficiency are related to an increased risk of developing metabolic syndrome over time. These findings show that in non-obese males, low SHBG and/or androgen insufficiency may offer early warning symptoms of cardiovascular risk and a chance for early intervention.

Less is known about how testosterone supplementation affects insulin resistance as measured by the homeostatic model assessment (HOMA) and glycemic management in diabetes mellitus as measured by HbA1c.In the absence of laboratory and other clinical indications of hypogonadism, it is premature to advocate testosterone therapy for metabolic syndrome or diabetes mellitus.

High-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) may be affected by testosterone replacement therapy in older men. A slight, dose-dependent reduction in total, LDL, and HDL cholesterol levels was observed in hypogonadal men in intramuscular testosterone esters and plasma lipids. the effects of androgens on abdominal obesity served as the mechanism for this effect. However, excessive levels of testosterone raise LDL levels while lowering HDL levels, which raises the risk of cardiovascular disease.

In older patients with chronic heart failure, testosterone therapy may improve insulin sensitivity as well as other cardiorespiratory and muscle outcomes. However, in individuals having coronary angiography, no reliable association between coronary atherosclerosis and the level of testosterone total or free has been found.

Increasing anemia

Androgens enhance reticulocyte count, hemoglobin, and bone marrow erythropoietic activity in addition to stimulating erythropoiesis. Hemoglobin concentration decreases by 10–20% when testosterone levels are low. Erythropoietin synthesis in the kidneys is increased by testosterone, which also promotes erythropoietic stem cells.

Cognitive function

A reduction in verbal, visual, and sensory memory and performance may be linked to a drop in testosterone levels. Particularly in older men, lower free testosterone levels appear to be linked to worse results on tests of cognitive function, and testosterone therapy in hypogonadal men may have some advantages for cognitive performance

Mood, energy, quality of life

In both replacement and supraphysiological levels, testosterone therapy has been shown to have effects on mood. testosterone therapy was discovered to have a positive impact on mood, particularly in individuals with hypogonadism and HIV/AIDS. the divergence in mood results may be explained by a genetic variation in the androgen receptor, which identifies a sensitive population in whom depression occurs when testosterone levels fall below a particular threshold.

Prostate tumor and benign prostatic hyperplasia (BPH)

there is unquestionable evidence that in men with locally advanced and metastatic prostate cancer, testosterone can promote development and aggravate symptoms. There are now insufficiently powered and well-designed long-term prostate disease facts to evaluate whether testosterone replacement therapy provides any additional risks. Prior to starting treatment, hypogonadal older men should receive advice on the potential risks and advantages of testosterone replacement therapy. They should also be closely checked for prostate safety during medication.

A man’s risk of prostate cancer must be evaluated before starting testosterone therapy utilizing, at minimum, a digital rectal examination (DRE) and the measurement of blood prostate-specific antigen (PSA) by adding additional risk indicators including age, family history, and nationality, the initial assessment can be enhanced. To support the clinician in determining the risk of prostate cancer, a number of tools have been developed such as an online prostate cancer risk calculator. These instruments have not been tested on andropause patients. Further evaluation may be necessary if the patient and doctor agree that the danger is high enough. However, routine requirements for preoperative prostate ultrasonography exams or biopsy should not advised.

Patients should have their prostates checked at 3-6 months, 12 months, and at least once a year after starting testosterone therapy. Transrectal ultrasound-guided prostate biopsies are recommended if the patient has a high enough prostate cancer risk suspicious result on digital rectal examination (DRE), elevated prostate-specific antigen, or as determined using a combination of the risk factors mentioned above.

Men who have undergone successful treatment for prostate cancer and who have been diagnosed with proven symptomatic hypogonadism are prospective candidates for testosterone replacement therapy after a reasonable delay. Since there are no long-term outcome data, practitioners in this situation must use excellent clinical judgment and be adequately informed about the benefits and risks of testosterone therapy. A clear discussion of the benefits and risks is required. With properly understood by the patient takeout routine follow-up must be essential

In hypogonadal patients with obesity, type 2 diabetes, and metabolic syndrome, lifestyle changes that focus mainly on increasing physical activity and weight loss are strongly advised. Regardless of how it is done, weight loss significantly reverses the hypogonadism linked to obesity.

Restriction for andropause

Men with prostate cancer or breast cancer should not use testosterone. There is debate about whether localized low-grade prostate cancer is a therapeutic restriction related or permanent. Prostate cancer, a palpable prostate nodule or induration, prostate-specific antigen levels greater than 4 ng/ml or greater than 3 ng/ml in men at significant risk for prostate cancer, such as African Americans or men with first-degree relatives who have the disease, severe lower urinary tract symptoms (LUTS) with an International Prostate Symptom Score, and other factors should all be considered before beginning testosterone therapy,

The suggestions from the International Society of Andrology (ISA), International Society for the Study of Aging Male (ISSAM), European Association of Urology (EAU), European Academy of Andrology (EAA), and American Society of Andrology (ASA); classify severe lower urinary tract syndrome symptoms indicated by a high international prostate symptom score because of benign prostate hyperplasia as a relative contraindication the testosterone therapy should not worsen lower urinary tract syndrome symptoms or promotes their progression. This restriction is partially valid when lower urinary tract blockage has received adequate and effective therapy.

Without first treating the underlying condition, males with significant erythrocytosis, a hematocrit greater than fifty percent, untreated obstructive sleep apnea (OSA), and poorly controlled or uncontrolled congestive heart failure shouldn’t begin testosterone therapy.

After treating sleep apnea in men with obstructive sleep apnea testosterone levels should be checked again.

Higher levels in hemoglobin and hematocrit as well as a little drop in high-density lipoprotein C are side effects of testosterone therapy in andropause males without underlying contraindications. There is no known clinical significance to these observations. The short research follow-up limits the quality of the current evidence about the safety of testosterone therapy in men in terms of patient-important outcomes.

Complications of the andropause

An elevated possibility of cardiovascular issues and osteoporosis (brittle bones), pneumonia, loss of function, and deconditioning should be issues related to andropause.

Lifestyle modifications for andropause

Lifestyle modifications to assist with low testosterone symptoms, Several lifestyle modifications described below may benefit symptom management if an individual has low testosterone.

Stress reduction

Using stress-reduction methods, such as journaling, meditation, or some other strategy, is a good idea. Avoiding caffeine, alcohol, and nicotine while focusing on relaxing techniques like deep breathing

Consuming a well-balanced diet

At all phases of life, it’s crucial to begin a healthy lifestyle modification such as consuming a balanced diet. Your diet might be an important consideration if you’re having mood swings or having trouble sleeping. Make sure to consume enough water, and a variety of fruits and vegetables on a daily basis, and stay away from junk food and sugars.

Exercise

A 10- to 15-minute walk after a meal can be very useful, as can a yoga or swimming class that is easy on the joints and good for the mind. Workout doesn’t have to involve running a marathon.

Join a social group.

With your family and friends, work to develop the togetherness. Cook meals with a group. Participate in a language class or book club. Participate in activities to prevent yourself from being detached. These clearly minor lifestyle adjustments must have a big effect on your overall health.

Summary

Andropause is a common condition that has a major effect on both personal and societal health due to its relationship with other age-related illnesses that cause significant morbidity and mortality in elderly men. Treatment with testosterone looks logical and beneficial given the links between androgen shortage and the risks of osteoporosis, memory loss, metabolic malfunction, and sexual life. However, varying findings from research analysis provide a partial picture of the complicated relationship between aging and androgen insufficiency.

Therefore, the presence of symptoms or signs and constant low serum testosterone levels are used to make the diagnosis of late-onset testosterone deficiency. There are some signs whose advantages are well-established. Before beginning testosterone therapy, the patient must be informed of the advantages and disadvantages of the medication, and the prostate should be evaluated as well as other risk factors. An aged male’s reaction to testosterone therapy should be evaluated, and if symptoms and signs do not improve, treatment should be stopped and the patient should be looked into for any other possible causes of the clinical findings. Finally, starting a testosterone treatment is not restricted by age.

FAQs

References

Singh, P. (2013, January 1). Andropause: Current concepts. Indian Journal of Endocrinology and Metabolism; Medknow. https://doi.org/10.4103/2230-8210.123552
In-Text Citation: (Singh, 2013)

Andropause – Causes, Symptoms, Treatment, Diagnosis – MedBroadcast.com. (n.d.). https://medbroadcast.com/condition/getcondition/andropause

The Journals of Gerontology: Series A, Volume 57, Issue 2, 1 February 2002, Pages M76–M99, https://doi.org/10.1093/gerona/57.2.M76

What is andropause? – Blog | Everlywell: Home Health Testing Made Easy. (n.d.). https://www.everlywell.com/blog/testosterone/what-is-andropause/.date accesses 21 sept 200