madman
Super Moderator
Abstract
Hypogonadism is a relatively rare condition in men, which increases in frequency as men age, but also as they become less active and gain weight. In the past 20 years, developing knowledge on the relationship between hypogonadism and cardiovascular and cerebrovascular health and on aspects of metabolic health has become clearer. The relationship between hypogonadism and specific endocrine abnormalities of spermatogenesis is much longer established. Long- and short-term testosterone replacement therapies have well-recognised effects on cardiovascular and cerebrovascular health and on aspects of metabolic health. This leads to a sense of safety when it comes to considering these options as ways of managing the recognised symptoms of hypogonadism and the hidden adverse findings. That confidence has yet to be proven by long-term randomised controlled studies. The use of exogenous gonadotrophins to raise endogenous testosterone levels is a cost-efficient method of achieving spermatogenesis but is not suitable for long-term testosterone maintenance therapy.
INTRODUCTION
Hypogonadism is characterized by a reduction in gonadal function, exhibited either as spermatogenic failure, deficiency of testosterone, or both. Testosterone deficiency is noted by decreased libido, impaired erectile function, muscle weakness, increased adiposity, depressed mood, and decreased vitality, but these are subtle symptoms in the adult male. If the cause is related to a failure of endocrine stimulation from the pituitary or higher, hormone stimulation to the testis will be low, resulting in hypogonadotrophic hypogonadism (with low testosterone and low FSH levels). Spermatogenic failure presents as oligo- or azoospermia, and consequent infertility. In recent years, evidence has been building that hypogonadism is associated with adverse events in the cardiovascular and metabolic systems, but more encouragingly, that testosterone replacement therapy appears to be beneficial in reducing the incidence of myocardial infarctions and cerebrovascular accidents[1]. If the cause is due to a testicular fault, there will be adequate or increased stimulation to the testis (with low testosterone levels and high FSH levels).
This paper addresses the relationship between hypogonadism and cardiometabolic disorders, recognizing the current evidence supporting the value of testosterone supplementation to improve outcomes in cardiovascular and metabolic diseases but also the need to be cautious in the absence of any long-term data to support testosterone replacement therapy in this way.
HYPOGONADISM AND CARDIOVASCULAR AND METABOLIC DISORDERS
EXTENT OF THE CONDITION
DIAGNOSTIC LIMITATIONS
IATROGENIC HYPOGONADISM
IDIOPATHIC HYPOGONADISM
HYPOGONADISM IN MEN LEADING TO INFERTILITY
CONCLUSION
What then should be the recommendation for managing hypogonadism in men with specific reference to long-term cardiovascular and metabolic diseases? Long-term (more than 8 years) data suggest that monthly testosterone supplementation injection appears to be beneficial in reducing the risk of both cardiovascular and cerebrovascular morbidity, and cardiovascular mortality[1,4]. Metabolic abnormalities are certainly affected for the better by short-term transdermal testosterone[8] and to a lesser extent in longer-term studies[1]. Short-term therapies to raise endogenous testosterone levels when the cause of the hypogonadism is in the pituitary or higher are effective in treating associated fertility problems, but their daily administration and cost make them unrealistic as long-term treatment options for testosterone replacement[26].
On the face of it, there may be some justification for giving all men over the age of 40 or older regular testosterone supplementation. However, as alluded to earlier in this paper, we caution against the over adoption of these therapeutic inventions in the absence of long-term, controlled studies to examine all the ramifications of these treatments. Interventions involving weight loss regimens such as those proposed by Wittert et al. are worth replicating, though Wittert et al. had a treatment arm with testosterone as well as a lifestyle intervention arm[30]. Separation of these two interventions would help to clarify which is more useful.
As a note of caution, it is imperative to remember how gynaecologists and reproductive endocrinologists prescribed estrogen replacement therapy (HRT) for women until a series of papers in the early 1990s blew the use of HRT in women out of the water - the more regrettable as many of those studies were incorrectly reported on and later had doubts cast on them. Our view would be that in the absence of prospective RCTs, treatments should be provided to those with low testosterone and symptoms and/or signs only.
Hypogonadism is a relatively rare condition in men, which increases in frequency as men age, but also as they become less active and gain weight. In the past 20 years, developing knowledge on the relationship between hypogonadism and cardiovascular and cerebrovascular health and on aspects of metabolic health has become clearer. The relationship between hypogonadism and specific endocrine abnormalities of spermatogenesis is much longer established. Long- and short-term testosterone replacement therapies have well-recognised effects on cardiovascular and cerebrovascular health and on aspects of metabolic health. This leads to a sense of safety when it comes to considering these options as ways of managing the recognised symptoms of hypogonadism and the hidden adverse findings. That confidence has yet to be proven by long-term randomised controlled studies. The use of exogenous gonadotrophins to raise endogenous testosterone levels is a cost-efficient method of achieving spermatogenesis but is not suitable for long-term testosterone maintenance therapy.
INTRODUCTION
Hypogonadism is characterized by a reduction in gonadal function, exhibited either as spermatogenic failure, deficiency of testosterone, or both. Testosterone deficiency is noted by decreased libido, impaired erectile function, muscle weakness, increased adiposity, depressed mood, and decreased vitality, but these are subtle symptoms in the adult male. If the cause is related to a failure of endocrine stimulation from the pituitary or higher, hormone stimulation to the testis will be low, resulting in hypogonadotrophic hypogonadism (with low testosterone and low FSH levels). Spermatogenic failure presents as oligo- or azoospermia, and consequent infertility. In recent years, evidence has been building that hypogonadism is associated with adverse events in the cardiovascular and metabolic systems, but more encouragingly, that testosterone replacement therapy appears to be beneficial in reducing the incidence of myocardial infarctions and cerebrovascular accidents[1]. If the cause is due to a testicular fault, there will be adequate or increased stimulation to the testis (with low testosterone levels and high FSH levels).
This paper addresses the relationship between hypogonadism and cardiometabolic disorders, recognizing the current evidence supporting the value of testosterone supplementation to improve outcomes in cardiovascular and metabolic diseases but also the need to be cautious in the absence of any long-term data to support testosterone replacement therapy in this way.
HYPOGONADISM AND CARDIOVASCULAR AND METABOLIC DISORDERS
EXTENT OF THE CONDITION
DIAGNOSTIC LIMITATIONS
IATROGENIC HYPOGONADISM
IDIOPATHIC HYPOGONADISM
HYPOGONADISM IN MEN LEADING TO INFERTILITY
CONCLUSION
What then should be the recommendation for managing hypogonadism in men with specific reference to long-term cardiovascular and metabolic diseases? Long-term (more than 8 years) data suggest that monthly testosterone supplementation injection appears to be beneficial in reducing the risk of both cardiovascular and cerebrovascular morbidity, and cardiovascular mortality[1,4]. Metabolic abnormalities are certainly affected for the better by short-term transdermal testosterone[8] and to a lesser extent in longer-term studies[1]. Short-term therapies to raise endogenous testosterone levels when the cause of the hypogonadism is in the pituitary or higher are effective in treating associated fertility problems, but their daily administration and cost make them unrealistic as long-term treatment options for testosterone replacement[26].
On the face of it, there may be some justification for giving all men over the age of 40 or older regular testosterone supplementation. However, as alluded to earlier in this paper, we caution against the over adoption of these therapeutic inventions in the absence of long-term, controlled studies to examine all the ramifications of these treatments. Interventions involving weight loss regimens such as those proposed by Wittert et al. are worth replicating, though Wittert et al. had a treatment arm with testosterone as well as a lifestyle intervention arm[30]. Separation of these two interventions would help to clarify which is more useful.
As a note of caution, it is imperative to remember how gynaecologists and reproductive endocrinologists prescribed estrogen replacement therapy (HRT) for women until a series of papers in the early 1990s blew the use of HRT in women out of the water - the more regrettable as many of those studies were incorrectly reported on and later had doubts cast on them. Our view would be that in the absence of prospective RCTs, treatments should be provided to those with low testosterone and symptoms and/or signs only.
