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 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Modern research in male contraception is focusing on 4 areas: 1) hormonal control of spermatogenesis, the complex processes of spermiogenesis in the testis where the spermatogonia stem cells mitotically divide into spermatocytes, which meiotically divide into nondividing spermatids, which become the spermatozoa; 2) direct (nonhormonal) inhibition of spermatogenesis; 3) the suppression of sperm maturation in the epididymis; and 4) the immunological suppression of fertility through the identification of an antisperm antibody. Hormonal suppression of spermatogenesis requires depression of testosterone levels in the testis, either by direct inhibition of the Leydig cells or by inhibition of the hypothalamic production of luteinizing hormone-releasing hormone, which induces the pituitary secretion of luteinizing hormone, which induces the secretion of testosterone. Testosterone suppression in the testis must be accompanied by exogenous androgen supplements or there will be loss of libido and potency. Preparations under investigation in the hormonal suppression of spermatogenesis include monthly injections of 200 mg depot medroxyprogesterone acetate with 200 mg testosterone enanthate; danazol with testosterone enanthate; anabolic steroids, such as 19-NT-hydroxyphenylpropionate; cyproterone acetate, an antiandrogen with progestational effects; and luteinizing hormone-releasing hormone agonists, which down-regulate pituitary receptors, or luteinizing hormone-releasing hormone antagonists, which competitively block receptor activation. None of these preparations have yet struck a balance where they can completely but reversibly block spermatogenesis at doses which do not have toxic or feminizing effects. 3 nonhormonal agents which suppress sperm production are gossypol, extract of Trypterigium wilfordii, and tolnidamine. Gossypol, an extract of cottonseed oil, has been widely studied in China and has been found 99% effective in producing azoospermia or severe oligospermia. However, it is extremely toxic, damages cells in the seminiferous epithelium, and causes hypokalemia. Over time, its effects become irreversible, and its mutagenicity and teratogenicity are not known. Agents which suppress sperm maturation in the epididymis act after cell division is complete and hence are not mutagenic, but they are extremely toxic. Alpha-chlorohydrin and 6-chloro-6 deoxysugars act by inhibiting the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase with the result that sperm cannot metabolize sugar. The sulfonamide compound, sulfasalazine, disrupts sperm motility by a mechanism not yet known. The development of a contraceptive vaccine relies on the identification of the antigenic determinants on sperm surface. Even if such a vaccine could be developed, there remains the problem of reversibility. None of the methods now being studied have demonstrated that they can reliably prevent unwanted pregnancy, and none have been around long enough for their longterm side effects to be known.
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PMID:Male contraception: current status and future prospects. 307 64

Daily afternoon injections of 25 micrograms melatonin for 12 weeks had no effect on testicular weights of male rats kept in long photoperiod (14L:10D); similarly, exposure of rats to short photoperiod (2L:22D) had no effect on gonadal weight. However, rats maintained in a long or short photoperiod and implanted every 2 weeks with a 15 mm Silastic pellet containing testosterone showed a significant reduction in testicular weight; this effect was more pronounced in rats exposed to a short photoperiod. Melatonin injections in testosterone-treated rats in a long photoperiod exacerbated the inhibitory effects of testosterone alone. Subcutaneous 2-weekly implants of a beeswax pellet containing 1 mg melatonin reversed the effects of the melatonin injections on relative testicular weights but not those due to short photoperiod exposure. Testosterone implants significantly reduced pituitary LH values in long and short photoperiod-exposed animals, more particularly in those exposed to short photoperiod. Melatonin injections alone or in combination with melatonin pellets did not further exaggerate the depression in pituitary LH due to testosterone alone in long photoperiod-exposed animals; similarly melatonin pellets did not reverse the depression in pituitary LH observed. No significant differences in plasma prolactin concentrations or in thyroxine concentrations or free thyroxine index were observed after any combination of treatments. We therefore suggest that the effects observed with short photoperiod may be due to melatonin.
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PMID:Influence of melatonin on the testicular regression induced by subcutaneous testosterone pellets in male rats kept in long or short photoperiod. 333 85

The effects of some androgenic-myotrophic steroids on pubertal ovulation in rats were studied. Treatment began at age 32 days. Steroids were given subcutaneously for 14 consecutive days. Autopsy was on the fifteenth day. The control animals showed an ovulation rate of 98% (137/140 rats). All of the steroids tested suppressed ovulation but differed in their potencies. Testosterone (7 rats ovulating/10 in group), dihydrotestosterone (5/10), nortestosterone (4/10), and norethandrolone (6/10) showed inhibitory effects at a dose of 20 micrograms/day. Nortestosterone seemed most effective, reducing ovulation to 10% at a daily dose of 40 micrograms. Androstenedione, methandrostenolone, oxymetholone, oxandrolone, ethylestrenol, and stanozolol required doses of 100 micrograms or more to depress ovulation. With most of the steroids the ovarian weight depression correlated exactly with ovulation suppression in regard to dose. Half of the compounds decreased uterine weight at lower doses but increased it at higher doses within the dosage range (1-4000 micrograms/day). Dihydrotestosterone, oxymetholone, and ethylestrenol caused uterine weight depression, norethandrolone caused uterine weight stimulation, and oxandrolone had no significant effect on this variable. All of the compounds except testosterone, methandrostenolone, and oxymetholone failed to increase body weight. The ovulation suppression, reduced ovarian weight, and reduced uterine weight observed probably are associated with antigonadotropic activity. For purposes of human contraception it is hoped a separation can be achieved by molecular modification between androgenicity and antiovulatory activity.
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PMID:Anti-ovulatory effects of some androgenic-myotrophic steroids in the pubertal rat. 465 Jun 62

There is an increasing awareness that androgens are of therapeutic value in postmenopausal women. Evidence is emerging demonstrating the role of testosterone in both female embryologic development and normal sexual behavior and mood. Women who are androgen depleted develop physical and behavioral symptoms referred to as female androgen deficiency syndrome. To a lesser degree, women who undergo an oophorectomy are deprived of endogenous ovarian androgens and have consistently been shown to have impairment of sexual functioning, loss of energy, depression, and headaches. Testosterone seems to act synergistically with estrogen in the treatment of these symptoms. The combination of estradiol and testosterone has been shown to have a beneficial effect on the skeleton, although not significantly better than estradiol therapy alone. Cosmetic side effects are rare if supraphysiologic doses are avoided. The potential metabolic complications have not been consistently demonstrated in studies to date. Androgen replacement therapy is a neglected area of medical practice and further research is needed to identify all women who will benefit from it since studies in menopausal women have shown parenteral administration to be well tolerated and safe. Such therapy is underused and very much underresearched. While testosterone implants work adequately, it would be more desirable and convenient to use a testosterone patch and safer, more effective oral androgens, if these products were available.
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PMID:Exogenous androgens in postmenopausal women. 782 43

In postnatal infants, there is similarity between the time course of transient gonadal steroid secretion and the age-related incidence of sudden infant death syndrome (SIDS). The cause of death in SIDS is generally thought to be a ventilatory arrest, but the mechanism responsible for such an event remains unknown. Testosterone has been demonstrated to depress ventilatory drive and increase sleep apnea in adult men. We tested the hypothesis that the gonadal steroid testosterone depresses infant ventilatory drive during sleep. Three newborn male infant primates were gonadectomized after birth. Ventilation was observed and quantified for each animal during completely natural unencumbered sleep by plethysmography for an average of 16 wk. Ventilatory patterns were recorded, and ventilatory drive was challenged with hypercapnia and hypoxia during quiet sleep on the night before and the night after testosterone administration. Hypercapnic ventilatory drive during sleep was significantly depressed by an average of 33.6% on the night after compared with the night before testosterone administration. Depression of the response to hypercapnia after testosterone was not accompanied by any change in resting minute ventilation measured during quiet sleep. Hypoxic ventilatory drive, incidence of apneic events, and length of apnea were not different after testosterone. The effects of injecting a placebo on ventilatory patterns and drive were tested by giving the placebo to all animals on several test weeks. Placebo injections produced no significant change in any measured parameters. These results support the hypothesis that testosterone depresses hypercapnic ventilatory drive during sleep in the infant primate.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Depression of hypercapnic ventilatory drive by testosterone in the sleeping infant primate. 804 60

This open, prospective therapeutic trial studied the effects of regular moderate androgen supplementation on bone mineral density in eugonadal men with established osteoporosis, and collected data on the safety of androgen therapy used in this setting. 23 men, aged 34-73 years, with vertebral crush fractures and back pain, in whom secondary causes of osteoporosis had been excluded, were treated with fortnightly intramuscular injections of 250 mg testosterone esters (Sustanon 250(R)) for 6 months. Blood pressure was recorded monthly; fasting lipids, glucose, haematocrit, plasma viscosity, and testosterone levels were measured every 3 months. Psychological effects were assessed using the Hospital Anxiety and Depression Scale (HADS) and General Health Questionnaire (GHQ), together with questioning on libido changes. Principal outcomes measured were changes in bone mineral density at the hip and spine by dual-energy X-ray absorptiometry (DEXA) over the treatment period. 21 men completed the study period. Mean bone mineral density at the lumbar spine increased from 0.799 g/cm(2) to 0.839 g/cm(2) during treatment (p < 0. 001), a rise of 5% in 6 months. Bone mineral density at the hip did not change. There were significant, favorable changes in diastolic blood pressure (-4.7 mmHg, p < 0.01), serum triglyceride levels (-0.405 mmol/L,p < 0.01), and total cholesterol (-0.27 mmol/L, p < 0.05). Adverse changes included a fall in HDL cholesterol (-0.087 mmol/L, p < 0.05) and a rise in plasma viscosity which was significant at 3 months but not at 6 months. The expected rises in hematocrit (0.434 to 0.456) and FAI (0.504 to 0.887) occurred. We conclude that testosterone supplementation significantly increased bone mineral density in this heterogeneous group of men with idiopathic primary osteoporosis, without an overall adverse effect on cardiovascular risk factors. This treatment warrants further evaluation in a randomized, controlled trial.
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PMID:Androgen supplementation in eugonadal men with osteoporosis-effects of 6 months of treatment on bone mineral density and cardiovascular risk factors. 883 11

Hypertension is often cited as a risk factor for erectile dysfunction. To clarify the relation between hypertension and erectile dysfunction, we evaluated 32 consecutive hypertensive and 78 normotensive impotent men with respect to multiple potential determinants and parameters of erectile function, including medical and sexual history, depression, hormonal profile, penile nocturnal tumescence, penile vascular supply, and pudendal nerve conduction. The hypertensive men were older, had higher body mass index, and used more medications than the normotensive men. The groups were not different with respect to the prevalence of smoking and peripheral vascular disease, but the hypertensive men had a marginally higher rate of ischemic heart disease (P = .06). The prevalence of depression, abnormal nocturnal penile tumescence, anomalous pudendal nerve conduction, and impairment in arterial supply as determined by penile brachial index were similar in the two groups. Testosterone and bioavailable testosterone levels were lower in the hypertensive men. After stratification by age and body mass index, hypertensive men younger than 50 years with body mass index less than 30 kg/m2 had significantly lower testosterone levels (12.0 +/- 1.7 versus 21.3 +/- 1.4 nmol/L, P < .02) but not bioavailable testosterone levels (3.9 +/- 0.7 versus 6.4 +/- 0.7 nmol/L, P < .17) than the corresponding normotensive group. Prolactin, follicle-stimulating hormone, and luteinizing hormone levels of the two groups were not significantly different. Contrary to common belief and with the exception of lower circulating testosterone levels, the overall analysis showed little difference between hypertensive and normotensive men with respect to a wide range of classic determinants of erectile function. Direct study of the local vascular erectile apparatus appears necessary for further elucidation of the mechanisms underlying erectile dysfunction in hypertensive men.
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PMID:Erectile dysfunction in hypertensive subjects. Assessment of potential determinants. 890 35

Changes in circulating glucocorticoid and androgen levels mediate agonistic behaviors in many vertebrates. Individual variation in the magnitude of the glucocorticoid response to stressful stimuli, the negative effects of elevated glucocorticoid levels on androgen levels, or both could mediate individual differences in subsequent agonistic behavior. In a series of previous studies, we found that both alternative male reproductive morphs in the tree lizard, Urosaurus ornatus, can exhibit elevated levels of plasma corticosterone following male-male encounters, but that the territorial morph appears less likely to exhibit coincident decreases in plasma testosterone. Two studies tested the hypothesis that the two morphs differ in the degree to which testosterone levels are influenced by elevated corticosterone levels. In the first study, physically restraining males elicited endogenous elevations of circulating corticosterone levels. Testosterone levels were significantly negatively correlated with corticosterone levels in the nonterritorial morph, but there was no correlation between levels of the two steroids in territorial males. In the second study, corticosterone levels were artificially elevated in free-living male tree lizards using a noninvasive dermal patch. This exogenous elevation of corticosterone significantly depressed testosterone levels in both morphs, but it produced a significantly greater depression in the nonterritorial morph. Nonterritorial males appear to be more sensitive than territorial males to the testosterone-suppressing effects of elevated circulating levels of corticosterone. This difference between the morphs in the effects of a stress hormone on the reproductive axis may be a fundamental part of the mechanism (1) underlying behavioral tactic switching within the nonterritorial morph or (2) contributing to behavioral differences between the morphs.
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PMID:Male morphs in tree lizards have different testosterone responses to elevated levels of corticosterone. 924 35

The effect of acute testosterone administration on exercise-induced myocardial ischemia was assessed in 14 men with coronary artery disease and low plasma testosterone concentrations in a study of randomized, double-blind, crossover design. Testosterone increased time to 1-mm ST-segment depression compared with placebo by 66 (15 to 117) seconds (p = 0.016), suggesting a beneficial effect of testosterone on myocardial ischemia in these patients.
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PMID:Effect of acute testosterone on myocardial ischemia in men with coronary artery disease. 1007 36

The temporolimbic structures of the brain that subserve emotional representation are highly epileptogenic and play an important role in the modulation of hormonal secretion and mediation of hormonal feedback. Estrogen is highly epileptogenic and exerts energizing and antidepressant effects. Excessive estrogen influence produces anxiety, agitation, irritability, and lability. It can promote the development of anxiety manifestations (e.g., panic, phobias, and obsessive-compulsive disorder). Progesterone and its metabolites inhibit kindling and seizure activity. They have potent anxiolytic effects, possibly by virtue of their GABAergic activity. Excessive progesterone influence produces sedation and depression. Testosterone has two major metabolites: estradiol, which can exacerbate seizures, and dihydrotestosterone, which blocks NMDA-type glutamate transmission and may be responsible for antiseizure effects. Testosterone has energizing effects and increases sexual desire in both men and women. In excess, however, it may promote aggressive, impulsive, and hypersexual behavior. Hormonal effects tend to be exaggerated or idiosyncratic in the setting of an abnormal or anomalous temporolimbic substrate, especially temporolimbic epilepsy. This may reflect altered neuronal responsivity to hormonal exposure perhaps by virtue of changes in the number of dendritic spines and receptors.
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PMID:Psychoneuroendocrine aspects of temporolimbic epilepsy. Part I. Brain, reproductive steroids, and emotions. 1010 Apr 30


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