Dr. SK Wangnoo and Dr. Asim Siddiqui detail on the clinical diagnosis and treatment/management approach to the processes of ageing in men and women- andropause, menopause, and somatopause.

It is inevitable that all of us have to undergo the ageing process! It is a normal, natural phenomenon and is a part of the life-cycle. With advancing age, there many changes in the human body regulated by the metabolic milieu, in part due to response to the decreasing hormonal reserves. That brings about the changes not only in the quality of life but also metabolic alterations like insulin resistance, distribution of body fat, bone health dynamics and sleep patterns. There is also social impact leading to loneliness, dependency and financial responsibilities. I am not going to comment on the social aspects, rather I will be commenting on the medical aspects of going on the “other side of fifty – Fifty Plus Blues!”.

In general, ageing is associated with alterations in the male and female hormones. For the purpose of simplistic differentiation, it is known by different common names as below:

• Menopause due to declining levels of oestrogen
• Andropause due to declining levels of testosterone
• Somatopause due to declining levels of growth hormone

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Menopause

The diagnosis of menopause is clinical rather than based on laboratory investigations (there is no need to do hormonal evaluation unless in specific situations) as is commonly perceived. Diagnose the following without laboratory tests in otherwise healthy women aged over 45 years with menopausal symptoms:

• perimenopause based on vasomotor symptoms and irregular periods
• menopause in women who have not had a period for at least 12 months and are not using hormonal contraception

Hot flashes and night sweats, are the hallmarks of menopause, although it is not necessary that all women experience these symptoms. Other symptoms include sleep disturbances, vague aches and pains especially in the joints and vaginal dryness. Manifestations like anxiety, irritability, depression, palpitations, skin dryness, loss of libido, and fatigue which are generally attributed to menopause, are unpredictable and do not have any direct correlation with the onset of menopause. These may start in the years before the final menstrual period and can last, from a few years to more than 10 years. Apart from the symptomatic concern which are the usual presenting features, it is important to emphasise on a few other things also - bone health, smoking cessation, alcohol use, cardiovascular risk assessment and management, and cancer screening and prevention.

The symptoms are sometimes quite frustrating to have and to treat. Choice of therapy is ideally based on available evidence regarding safety and efficacy and is generally a shared decision including both patient and provider. The treatment selected should be tailored to the individual patient and vary according to each woman's symptom severity, age, medical profile and personal preference. The treatment options are:

• Hormone replacement therapy (HRT)
• Non-hormonal
• Non-pharmaceutical, for example cognitive behavioural therapy (CBT)

For menopausal women <60 years of age or <10 years past menopause with bothersome vasomotor symptoms who do not have contraindications or excess cardiovascular or breast cancer risks and are willing to take menopausal hormone therapy, may be initiated on oestrogen therapy for those without a uterus and oestrogen plus progestogen therapy for those with a uterus. Other options for relief of troublesome vasomotor symptoms are usually the over-the-counter or complementary medicine therapies, like black cohosh, omega-3-fatty acids, red clover, vitamin E, and mind/body alternatives including anxiety control, acupuncture, paced breathing, and hypnosis, although it is unlikely that any of these has a remarkable benefit.

For those with cardiovascular and breast cancer risks, non-hormonal replacement (SSRIs/SNRIs or gabapentin or pregabalin) therapies are the preferred choice. The cardiovascular issues relating to hypertension, lipids and diabetes are to be treated as they would be addressed to in any individual.

Bone health is one of the major issues in the post-menopausal age group. Exercise, adequate calcium and vitamin D replacement, cessation of smoking and osteoporosis specific therapies may be used as per necessity.

For postmenopausal women with genito-urinary symptoms of, a trial of vaginal moisturisers may be used at least twice weekly.

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Andropause

Andras in Greek means human male and Pause in means cessation aptly describes this condition. It is due to age-related decline in testosterone concentrations which begins after the age of 40 years. The annual decline in total and free testosterone is 1.0%, and 1.2%, respectively. It is also called as male menopause/male climacteric/androclise/Androgen Decline in the Ageing Male (ADAM)/Ageing Male Syndrome (AMS).

In contrast to menopause which is a universal, well-characterised timed process due to gonadal failure, andropause is characterised by a rather insidious onset and slow progression. The rate of decline in testosterone levels is variable and is affected by multiple factors like chronic diseases and medications; and this decline can be reduced to some extent by the management of lifestyle factors. Waist circumference is one of the potentially modifiable risk factors for low testosterone and symptomatic androgen deficiency.

Testosterone threshold at which symptoms become manifest show individual variation and many men are not symptomatic, although having low levels of testosterone. There is still disagreement regarding on how to define the syndrome for clinical and epidemiological research purposes. It is either purely statistical (lower 2.5th percentile of testosterone adult value) for epidemiological studies, or is based on symptom questionnaire like Androgen Deficiency in the Aging Male. The outlier here are the disassociation between biochemical levels and the symptoms.

Symptoms associated with declining testosterone levels are low libido, erectile dysfunction, decreased muscle mass and strength, increased body fat, decreased bone mineral density and osteoporosis, and decreased vitality and depressed mood, but none of these symptoms are specific to the low androgen state, but may raise suspicion of testosterone deficiency. One or more of these symptoms must be corroborated with a low serum testosterone level.

Serum testosterone levels vary significantly as a result of circadian and circannual rhythms, episodic secretion, and measurement variations. When testing, the sample for total testosterone determination should be obtained between 0700 and 1100 h.

Testosterone replacement therapy decreases fat mass and increased lean body mass with no overall change in body weight. Other expected benefits of these changes of body composition on strength, muscle function, and metabolic and cardiovascular dysfunction are suggested by available data but require confirmation by large-scale studies.

Osteopenia, osteoporosis, and fracture prevalence rates are greater in hypogonadal younger and older men, who respond to testosterone replacement. Serum-free testosterone has been found to be significantly correlated with libido, erectile, and orgasmic function domains. Testosterone replacement may moderately improve nocturnal erections, sexual thoughts and motivation, number of successful intercourses, scores of erection function, and overall sexual satisfaction. Testosterone has a positive effect on reducing the risk factors for metabolic syndrome and cardiovascular disease, anaemia, cognitive function, mood, energy, and quality of life.

Presently there is no conclusive evidence that testosterone treatment increases the risk of prostate cancer or BPH, however, there is unequivocal evidence that testosterone can stimulate growth and aggravate symptoms in men with locally advanced and metastatic prostate cancer. Always assess for the risk of prostate cancer prior to initiating replacement.

The replacement may be in the form of intramuscular injections, oral patches and patches for skin application (which are gaining popularity). The selection of the preparation should be a joint decision of an informed patient and physician. Appropriate follow-up should be done with special emphasis on haematocrit, for PSA and worsening of OSA.

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Somatopause

The pathological phenomenon of somatopause, noticeable in hypogonadal ageing subjects, is based on the growth hormone (GH) production and secretion decrease along with the fall in GH binding protein and insulin-like growth factor 1 (IGF-1) levels, causing different musculoskeletal, metabolic, and mental issues.

GH secretion declines progressively as we age, and many age-related changes resemble those of the adult GH deficiency (GHD) syndrome - decrease in lean body mass; an increase in body fat, especially in the visceral/abdominal compartment; adverse changes in lipoproteins; and a reduction in aerobic capacity.

There are very few well-controlled studies of the effects and side effects of GH or GH secretagogues in aging. There is a consensus that GH has effects on body composition, but reports disagree on effects on psychological or physical functional performance. Older adults are much more susceptible to the dose-related side effects of GH, including peripheral oedema, carpal tunnel syndrome, and a variable decrease in insulin sensitivity; and it is not known whether chronic GH treatment affects the risk of malignancy or has other long-term risks. As of now, use of GH on treating somatopause is only indicated only of GH deficiency is demonstratable biochemically, although many use it as on “off-label” treatment.

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In a nutshell, everyone has to go through the ageing process – it is a part of the normal biology of ageing. There are metabolic alterations which accompany normal metabolic changes, but all are treatable either with medications or by adopting a healthy lifestyle. There is no 'one-size fits all' approach!

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 writer, Dr. Subhash Kumar Wangnoo is a Senior Consultant Endocrinologist and Diabetologist at Apollo Centre for Obesity, Diabetes and Endocrinology (ACODE) in New Delhi.

Dr. Asim Siddiqui is a Senior Consultant Endocrinologist at Apollo Hospital, New Delhi.