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PubMed1989

A new look to the andropause: altered function of the gonadotrophs.

After being controversial for a long time, the age associated decline in plasma T levels and secretion in normal men is now generally accepted. Although most data point towards a primary testicular origin for the decline in Leydig cell function, other data point towards alterations at the hypothalamo-pituitary levels: T levels in elderly men are decreased notwithstanding an important secretory reserve of both LC and gonadotrophs. Nycthemeral variations in plasma T levels are significantly decreased in elderly men. The increase in immunoreactive LH levels is dysproportionate to the increase of bioactive LH levels. Study of the activity of the LHRH pulse generator in 27 young and 21 elderly men revealed a significant decrease in frequency of high amplitude pulses for both LH and T. Moreover the sensitivity of the gonadostat to sex hormone feed back was significantly greater in the elderly men. Acute administration of an antiopoid (Naloxone), 2 mg i.v. both in young and elderly men at rest showed that in young and elderly men, Naloxone induced a comparable increase of LH levels. Naltrexone on the other hand increased LH pulse frequency in elderly but not in young men. The data show that opioids maintain their inhibitory effect on LHRH secretion in elderly men and suggest either that the opioid tone in the elderly men is decreased or that the response of the gonadotrophs to LHRH is decreased.

Adult↗
PubMed2003

Use of clomiphene citrate to reverse premature andropause secondary to steroid abuse.

OBJECTIVE: To report a case of symptomatic hypogonadism induced by the abuse of multiple steroid preparations that was subsequently reversed by clomiphene. DESIGN: Case report. SETTING: University-affiliated andrology practice within family practice clinic. PATIENT(S): A 30-year-old male. INTERVENTION(S): Clomiphene citrate, 100-mg challenge for 5 days, followed by treatment at same dose for 2 months. MAIN OUTCOME MEASURE(S): Clinical symptoms, androgen decline in aging male questionnaire, total T, FSH, LH. RESULT(S): Reversal of symptoms, normalization of T levels with LH surge, restoration of pituitary-gonadal axis. CONCLUSION(S): Clomiphene citrate is used typically in helping to restore fertility in females. This represents the first case report of the successful use of clomiphene to restore T levels and the pituitary-gonadal axis in a male patient. The axis was previously shut off with multiple anabolic steroid abuse.

Adult↗
PubMed2000

Andropause.

Although, in distinction to middle aged women, in middle aged men there does not occur a sudden arrest of gonadal functions, fertility persisting until very old age, aging in men is, nevertheless, associated with an gradual decline of both endo- and exocrine testicular function. Whereas age has in fact only minimal effects on the quality of the ejaculate, endocrine function declines steadily with age and at age 75 years, mean plasma testosterone levels are only 65% of levels in young adults whereas over 25%, of these men have bioavailable testosterone levels below the lower normal limit in young adults. The interindividual variations in the plasma levels are, however, very important and a quarter of men over 75 years old, have still testosterone levels within the upper quartile of values in young men. Aging is accompanied by a series of signs and symptoms, many of which are rather similar to those observed in young hypogonadal males. The etiology of these signs and symptoms is often multifactorial, and very few correlations have been found between symptoms and plasma testosterone levels. Nevertheless, there is good evidence that the age associated decrease in testosterone levels is at least a co-determinant of these symptoms and testosterone supplementation has shown favorable effects on many of them. Side effects of this substitutive therapy are minimal when care is taken to keep plasma testosterone levels within the physiological range. Clinical prostatic carcinoma is an absolute contra-indication for testosterone supplementation. So far, there are no indications that testosterone would stimulate the evolution of as subclinical prostatic carcinoma to a clinical carcinoma but it should be recalled that so far, only a small number of elderly males received substitutive androgen treatment for longer periods in controlled studies. Hence, although side effects are generally minimal, one should, nevertheless, await the results of larger, long term, well-controlled studies before to recommend the routine testosterone substitution of elderly men.

Aged↗
PubMed2001

Neuroendocrine aging in men. Andropause and somatopause.

Aging is accompanied by gradual but progressive reductions in the secretion of testosterone and growth hormone in men, and by alterations in body composition and functional capacity that, to some degree, undo the effects of puberty. Preventing or reversing these changes with the use of trophic factors, including androgens, growth hormone, and growth hormone secretagogues, is an appealing prospect, but documenting the effectiveness of these interventions and their benefits and risks has proven to be a difficult undertaking that is far from complete. Small-scale clinical studies have shown that it is practicable to boost growth hormone and IGF-1 levels for periods of up to 12 months, and testosterone for up to 36 months, to reverse at least some age-related changes in body composition. Information regarding the effects of these interventions on strength, exercise capacity, and the ability to perform activities of daily living is still sparse, and additional reports from recently completed or currently ongoing clinical trials will not provide sufficient data to make firm conclusions. From the limited information currently available, androgen supplementation may be of benefit in some men aged more than 65 years, particularly in men with low serum testosterone levels (< 2 ng/mL). In this group, supplemental androgen therapy would be expected to increase lean body mass, bone mass, and possibly strength. In older men with testosterone levels between 2 and 3.5 ng/mL, some benefit might result from androgen supplementation, but it is not yet clear whether the benefits outweigh the risks. For men in this category, one might consider a 6- to 12-month trial of therapy after a full discussion and explicit consent, followed by a reassessment of the value of ongoing treatment. The even more limited data on growth hormone or growth hormone secretagogue interventions in aging do not support their general clinical use in healthy older men. Growth hormone is much more expensive than testosterone and is not covered by insurance for off-label uses. Patients who persistently seek a trial of therapy should be encouraged to enroll in a study if one is locally available. All of the growth hormone studies reported to date have focused, generally for reasons of safety, on healthy and robust groups of older subjects, men in whom the need for intervention is least compelling and in whom the functional effects of treatment may be the most difficult to observe. Phase II studies of intermediate size and duration examining prefrail groups of elderly who are at greater risk for functional loss and who stand to benefit the most from either preventive or restorative interventions are underway but are limited to the intermediate outcomes of body composition, strength, and function. Trials designed to assess clinically relevant final outcomes, such as falls, fractures, and institutionalization, are of necessity large-scale, long-term, and expensive. Support for larger phase III studies of growth hormone is unlikely to be forthcoming until the phase II studies are completed and show further promise. A multicenter clinical trial of testosterone is currently being planned under the joint sponsorship of the National Institute on Aging, the Veterans Health Administration, and industry, aimed at assessing the effects of testosterone on the risk for falls and fractures. The results of this trial and other large clinical trials should help to better define the balance of benefits and risks of trophic factor intervention in normal older men.

Aging↗
PubMed2002

Impact of obesity on hypogonadism in the andropause.

Obesity is an issue that is increasingly affecting ageing men. With ageing, there is a decline in androgens as well. There are implications for the health of ageing men as a result of hypogonadism. Overall, there seems to be an inverse relationship between body mass index and testosterone levels, as is also demonstrated in our cross-sectional study. Obesity seems to depress the production of testosterone. It has been hypothesized that there is increased aromatization of testosterone to oestradiol and alteration of the hypothalamic-pituitary-adrenal axis in obese older men. Some hormones can affect obesity in ageing men including leptin, insulin, dehydroepiandrostenedione and growth hormone. The relationship of obesity to these hormones in ageing men will be reviewed. Testosterone replacement in ageing men can alter body composition whereby fat is exchanged for muscle. These studies will also be reviewed. Further studies in this field are recommended to evaluate long-term benefits and risks.

Aged↗
PubMed2003

The polymorphic androgen receptor gene CAG repeat, pituitary-testicular function and andropausal symptoms in ageing men.

The activity of androgen receptor (AR) is modulated by a polymorphic CAG trinucleotide repeat in the AR gene. In the present study, we investigated hormonal changes among ageing men, and whether the number of AR CAG triplets is related to the appearance of these changes, as well as symptoms and diseases associated with ageing. A total of 213 41-70-year-old men donated blood for hormone analyses (LH, testosterone, oestradiol and SHBG) and answered questions concerning diseases and symptoms associated with ageing and/or androgen deficiency. Of these men, 172 donated blood for the measurement of the CAG repeat length of AR. The CAG repeat region of the AR gene was amplified by polymerase chain reaction (PCR) and the products were sized on polyacrylamide gels. The repeat number was analysed as a dichotomized variable divided according to cut-off limits of the lowest (< or =20 repeats) and the highest quartile (> or =23 repeats), and as a continuous variable. The proportion of men with serum LH in the uppermost quartile (>6.0 IU/L) with normal serum testosterone (>9.8 nmol/L, above the lowest 10%) increased significantly with age (p = 0.01). There were fewer men with this hormonal condition among those with CAG repeat number in the uppermost quartile (> or =23 repeats) (p = 0.03). These men also reported less decreased potency (p < 0.05). The repeat number was positively correlated with depression, as expressed by the wish to be dead (r = 0.45; p < 0.0001), depressed mood (r = 0.23; p = 0.003), anxiety (r = 0.15; p < 0.05), deterioration of general well-being (r = 0.22; p = 0.004), as well as decreased beard growth (r = 0.49; p < 0.0001). A hormonal condition where serum testosterone is normal but LH increased is a frequent finding in male ageing. Only certain types of age-related changes in ageing men were associated with the length of the AR gene CAG repeat, suggesting that this parameter may play a role in setting different thresholds for the array of androgen actions in the male.

Adult↗