|Medical Solutions for the 21st Century . . .|
|Meeting Tomorrow's Challenges Today|
Highlights From the VII
June 15-19, 2001
E-Newsletter No. 6
The world’s top experts addressed the latest research and developments in the diagnosis and management of male infertility and male sexual dysfunction. These exciting developments will not only affect the future of andrology, but will also result in benefits to patients, the medical profession, and to health care services.
The scientific program featured leaders in the fields of male aging, stem cells/germ cell engineering (gene transplanting), androgen action, genetics of spermatogenesis, male sexual dysfunction, prostate cancer, assisted reproductive therapies (ART)/intracytoplasmic sperm insertion (ICSI), testicular cancer, sexually transmitted diseases, cell survival, sperm egg interactions, and ethical and public issues in matters affecting the male reproductive system (andrology).
The meeting was preceded with a post-graduate course on Recent Advances in Clinical Andrology. The course included presentations on the pharmacological (use of drugs and other chemicals) management and prevention of erectile dysfunction (ED), gene therapy for ED, and state of the art lectures on the surgical management of ED, and obstructive azospermia (blockage of the passage of sperm for ejaculation and fertilization) among others.
Following the end of the congress program, another post-graduate course was provided for Andrology Laboratory Techniques. The purpose of this course was to educate participants about aspects of sperm function testing, and how they relate to the current and likely future editions of the World Health Organization Manual.
New drug products on the horizon for ED include two oral drugs with actions similar to Viagra, but with less risk of side effects and a longer period of action. Cialis and Vardenifil work like Viagra but have less risk of cardiovascular complications, visual changes, and low back pain. Uprima is administered as a sublingual tablet and has the side effect of nausea and possible vomiting with increased doses, but which may be needed for a good erectile response.
Two other drugs being developed are designed to work through direct brain stimulation. One of these will be a sublingual tablet. The other, will be an injectable (subcutaneous) product. MSH, a melanocyte stimulating hormone requires subcutaneous injection, and is soon to be entering stage III clinical trials for FDA approval. Both of these are believed to have stimulatory effects on libido, and may have potential beneficial effects on females as well.
Gene therapy for ED was discussed. The penis is deemed to be an ideal organ for gene therapy because of its external location, and only a small amount of cells are needed. Clinical trials on laboratory animals of this treatment have resulted in sustaining enhanced erectile function in older animals for up to 30 days. This may become the first application for gene therapy in aging.
Diabetes and ED are closely correlated. The onset of ED is an early indicator of Diabetes Mellitus developing in old age. ED will occur 20 years earlier. It was estimated that more than 15 million men and 50% of all cases of ED are at risk for this in the U.S. alone.
It is becoming evident that there is no gold standard of treatment for ED. Quality of life is not just a lifestyle issue. Multiple aspects of health involving the entire gamut of male aging are involved. No one drug will fix all. The future era of Sexual Medicine will involve multiple drug therapies.
Androgens and the Brain
A symposium on Androgens and the Brain discussed the How, When and Where of the mechanisms of action of Androgens in the Brain, Behavioral Effects and Cognitive Functions of Androgens in Men, and Androgen and Sexual Function.
Androgen action in the brain affect emotions, learning and memory, hormonal feedback, seizures, aggression, verbal fluency and visual-spatial mapping. Androgen receptors have been localized to numerous areas in the brain responsible for these functions. Stimulation of these receptors is required early in the post-natal period to have adequate brain development throughout life.
Androgen effect on cognitive (thought, perception, understanding and reasoning) function explains the "Male Cognitive Style." Men generally outperform women in visual-spatial tasks, whereas women generally outperform men on verbal fluency tasks and measurements of perceptual speeds.
Evidence suggests the androgen effect is a curvilinear response to testosterone levels, that is, it is not correlated with higher vs. lower levels of testosterone. Also, there is a differential effect: testosterone administration in hypogonadal males will increase visual-spatial functioning and decrease verbal fluency.
Estrogen dependency, such as increased manual dexterity while decreasing visual-spatial function with rising estrogen levels and the reversal during falling estrogen levels, are similar characteristics during the female menstrual cycle.
Androgens and Sexual Function
There seems to be no direct correlation with androgen levels and sexual function in humans. However, testosterone replacement restores sexual arousal, desire, and copulatory responses in laboratory animals. Also, female sexual response increases following administration of testosterone and estradiol in combination. Some of the testosterone effects in the brain have been shown to be due to the conversion of testosterone in the brain to estrogen and dihydrotestosterone (DHT). Thus, testosterone, estrogen and DHT have been shown to restore elements of sexual behavior.
DHT is the stimulatory growth factor responsible for full development of the external genitalia in males. A novel use of DHT may be the topical application to congenitally undersized genitalia to enhance penile growth.
Testosterone and the Aging Male
Total and free testosterone concentrations decline progressively with advancing age because of defects at all levels of hypothalamic-pituitary-testicular axis; however, the risks and health benefits of long-term testosterone remain poorly understood. Physiologic testosterone replacement of young, androgen-deficient men and older men with low testosterone levels is associated with an increase in fat-free mass, grip strength, and fractional muscle protein synthesis, but we do not know whether testosterone replacement improves quadriceps strength, power, muscle fatigability, and physical function in older men, and whether it can reduce the risk of disability and falls.
Testosterone replacement increases bone mineral density in young hypogonadal men and older men with low testosterone levels, but we do not know whether testosterone reduces fracture risk. Testosterone replacement improves sexual function in older men with low testosterone levels, but not in men with erectile dysfunction who have normal testosterone levels. Testosterone might improve visual-spatial skills, verbal memory, and verbal fluency in men with low testosterone levels. However, it is unknown whether testosterone supplementation can induce clinically meaningful changes in cognitive function in older men. Testosterone might also improve mood and sense of energy, but the effects of testosterone replacement on health-related quality of life have not been studied. Short-term administration of testosterone in replacement dose is safe, but the long-term risks of testosterone administration in older men remain unknown. The potential adverse effects of testosterone include the risk of erythrocytosis, induction or exacerbation of sleep apnea, gynecomastia, and increased risk of heart disease and clinically detectable prostate cancer.
Testosterone administration by increasing the intensity of PSA surveillance will likely lead to increased number of prostate biopsies, and increased detection of prostate cancers. It is possible that testosterone administration might make subclinical foci of prostate cancer grow and become clinically overt; we do not know what clinical impact this would have on patient morbidity and survival, and health-care costs. Because the efficacy of testosterone supplementation on health-related outcomes has not been demonstrated, and its risks remain largely unknown, it is premature to make a general recommendation of testosterone replacement of all older men with low testosterone levels. Until more information becomes available, testosterone administration in older men should be individualized, preceded by a careful discussion of its potential risks and benefits with the patient, and rigorous monitoring of potential adverse effects.
Androgens are contraindicated in men with carcinoma of the breast, or known or suspected carcinoma of the prostate. Geriatric patients treated with androgens may be at an increased risk for the development of prostatic carcinoma.
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