The nature of androgen action on male sexuality: Excess cortisol suppresses the central hypothalamic—pituitary axis, whether exogenous 52 or endogenous. What will your taper look like? The positive effects of testosterone on nocturnal erections have also been shown by others, who reported a positive effect in coital attempts, and in orgasms as well. Clin Endocrinol ; Of these men with low baseline testosterone levels, or June 23, at 6:
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Low testosterone production cannot support healthy sperm synthesis and thus, causes infertility. Because Clomid indirectly boosts testosterone levels in men, it can be used to treat infertility that results from low testosterone production. Clomid for Male Infertility Clomid is typically taken once a day, with a staring dose of 25 mg per day. However, the dosage often needs to be adjusted later on, as the individual response to the medication varies.
It is essential to find a dosage that supports optimal hormone production, because too high testosterone levels can decrease sperm count and cause other serious side effects. Testosterone, LH and FSH levels are typically re-tested within a few weeks after the therapy is started, and the dosage of clomiphine citrate is adjusted accordingly.
Popular subjects covered include: Patients from over 30 countries visit Dr. Can it Cure Low Sperm Count? The conversation around infertility has evolved in the past decade as a growing… Read More. Five Male Fertility Goals for In the Center for Sexual Function, men who presented with sexual dysfunction during a 2-y period were evaluated with retrospective chart review. The clinical characteristics and medical risk factors of the population were previously reported.
Of these men, Of the men with hypogonadotropic hypogonadism and ED, Most of these men were married in a stable heterosexual relationship; the single men were in a steady relationship for at least 6 months. A home log was kept in which the couple recorded the number of sexual attempts and successes at intercourse. The men who failed did not notice any change in their sexual activity.
No men reported side effects caused by clomiphene citrate. Of the men who began taking clomiphene, This population was the basis of the present study. Serum luteinizing hormone and free testosterone levels were drawn between Of these men with low baseline testosterone levels, or The normal range for free testosterone is age related and is reported as 9. Patients were categorized as having complete, partial, or no response based on self-reported erectile function following clomiphene therapy.
When ordinal categorical variables were compared, the linear-by-linear test of association was used. Paired t -tests were used to compare the mean hormone levels within each response group before and after treatment with clomiphene citrate. Paired t -tests were repeated to assess differences in age within response groups with selected comorbid conditions. Independent t -tests assuming equal variance were used to detect significant differences between response groups in the change or delta in luteinizing hormone and free testosterone levels following treatment.
Finally, multivariate analyses were conducted to determine the independent effects of patient characteristics and clinical risk factors on the likelihood of responding to clomiphene. The three response categories were collapsed into a binary variable, where 1 denoted any response to treatment ie, positive or partial and 0 denoted no response. Variables deemed clinically relevant or statistically significant in univariate analyses were selected for entry into multivariate models.
Diagnostic analyses eg, tests of multicollinearity and analysis of residuals were conducted to ensure that variables were appropriately entered in the model and critical statistical assumptions were not violated. When odds ratios for scaled predictors were large, regression models were run with and without the parameter of interest and goodness-of-fit statistics were then compared. All P values are two-tailed.
The mean age of the men was A total of 84 men Figure 1 shows the response rate of the group as a whole. In all, 67 men Figure 2 and Figure 3 show that despite a disparity in clinical response, clomiphene stimulation significantly raised the blood levels of both luteinizing hormone and free testosterone in all groups. The serum luteinizing hormone level rose in the responders from 3.
The serum-free testosterone levels rose from 9. Figure 4 shows the response to clomiphene as a function of age. There was a higher percentage of responders The partial responders were equally divided by age, Table 1 shows the influence of comorbid medical risk factors on the effect of clomiphene-stimulated testosterone levels on erectile function.
A higher number of partial responders and nonresponders were seen in patients with hypertension, diabetes mellitus, coronary artery disease CAD , and those using multiple medications; however, not all of these differences achieved statistical significance. In these comorbidities, the number of men who responded partially to testosterone replacement was between Men with psychosocial comorbidities to their hypogonadism seemed to respond better to correction of the low testosterone, between This appeared to be true for various types of stress, whether because of endogenous chronic anxiety, performance anxiety, or work-related stress.
It is interesting that significant performance anxiety was a greater problem for men who had a partial clomiphene response than for those with no response Table 2 correlates the medical risk factors diabetes, hypertension, CAD, and the use of multiple medications with age. Only the incidence of CAD however differed significantly by age Among partial responders, there was a higher percentage of younger men who had diabetes, CAD, and took multiple medications.
Again, only the incidence of CAD differed significantly by age In non-responders, there was a definite increase in the number of older men in all four of the major medical risk factors. Older nonresponders were significantly more likely to have hypertension than younger nonresponders In the anxiety categories, mild performance anxiety failure was significantly higher in younger responders Logistic regression analysis assessed the effects of relevant clinical variables while controlling for covariates.
Since many variables were inter-related, a correlation matrix was created to assess problems of multicollinearity that would bias regression coefficients and inflate standard error estimates. Plots of residuals and goodness-of-fit statistics for models with and without selected variables were then analyzed. Variables with extremely low frequencies or high correlations with one another were ultimately excluded, because these decrease the predictive validity of the model.
Table 3 shows the final logistic regression model and related parameter estimates. The absence of a venous leak, clinically manifested as early detumescence of sexually stimulated erections, was the second strongest predictor of therapeutic response. Diabetes was the only clinical predictor of patient response that approached statistical significance.
The narrow confidence interval around this estimate indicates that with a slightly higher sample size, the parameter would become significant at or below the 0. Contrary to published literature, cigarette smokers had virtually no difference in response compared with nonsmokers OR, 1. However, this estimate may be attributable to the low number of smokers in the sample. Finally, patients with CAD were 1.
The final three predictors illustrate the relations between previous clinical therapy for ED and clomiphene response. As a result of the wide variety of therapeutic options available to and used by these patients, three different categories were created: In contrast, the use of other therapeutic devices was a strong and significant predictor of response. Patients who had used alternative therapies were 3. A secondary regression analysis was conducted using backward deletion of parameters to create a bes t -fitting model.
Results confirmed the significance of the variables described previously. A multinomial logistic regression model was also run, using partial response, positive response, and no response categories as levels of the dependent variable. Parameters affecting therapeutic response in previous analyses did not differ significantly when the response was measured as three categories instead of two. Finally, tests for firs t -order interactions between age and clinical characteristics did not provide additional insights, and are therefore not included.
Our data showed that clomiphene citrate can successfully stimulate the hypothalamus to cause increased testicular testosterone production. It was also seen in the presence of common chronic conditions such as diabetes mellitus, hypertension, CAD, and the use of multiple medications. The fact that these conditions were also more prevalent in the older age group seems to indicate that the lack of clinical response may be the result of comorbid medical factors than of age alone.
It has long been established that testosterone is required for libido in men, but there has been debate regarding the extent of its effect on erectile capacity and sexual satisfaction. The positive effects of testosterone on nocturnal erections have also been shown by others, who reported a positive effect in coital attempts, and in orgasms as well. At the biochemical level, androgens are necessary for the physiologic erectile response in the corpus cavernosum of the penis.
As previously mentioned, acute critical illness decreases testosterone levels, especially by suppressing the central hypothalamic-pituitary axis. The effect may be mediated through cytokines produced in systemic diseases, including tumor necrosis factor. Iron deposition in the pituitary may cause hypogonadotropic hypogonadism in beta-thalassemia, 48 the effect of which was found to be separate from the production of diabetes in these patients.
Some central suppression of testosterone production was even found during fasting in younger men. A large percentage of our patients had anxiety-related disorders; some had chronic anxiety, while others had performance anxiety, but the most prominent was work-related stress. Excess cortisol suppresses the central hypothalamic—pituitary axis, whether exogenous 52 or endogenous.
Clomiphene stimulation did not elevate the testosterone level out of the normal range, but it remained in the middle of the normal range. Stimulation for 4 months produced levels similar to those in our previous study when the levels were measured after 2 months. Wang et al 58 found that a positive response to testosterone did not improve further when testosterone levels increased from the low-normal to the high-normal range.
Snyder et al 59 also found that increasing the testosterone level of normal, healthy males over the age of 65 to the level of young healthy males had no effect on energy, mental health, or sexual function. It was suggested that a low testosterone level might only represent a random spurious value. These low testosterone values also correlated with their presenting symptoms of libido and erectile difficulties.
It is also doubtful that the positive responses were due to a placebo effect, because the results were similar to our previous placebo-controlled study 11 and the home logs showed an increased intercourse rate that was verified by the partners. Our results also agree with those of Jain, 61 who showed a cause and effect relation between ED and low testosterone levels in a meta-analysis. The response rate was better in primary hypogonadsim than in secondary hypogonadism.
We agree with Jain's explanation that men with primary testicular failure have a clearer presentation and fewer comorbidities than in secondary testicular failure, a factor that tends to confound the picture in the latter situation. It does appear that many men may have functional suppression of the central component of their hypothalamic—pituitary—testicular axis resulting from a variety of acute and chronic medical conditions and multiple drug use.
The same is true for various types of anxiety. The testosterone level generally can be increased well into the normal range with the use of clomiphene citrate three times weekly. We have found clinically that if the primary cause of the problem is corrected, clomiphene can occasionally be tapered and stopped, and the testosterone level will remain normal unpublished observations. The total treatment rarely needs to be extended beyond 6 months. Quite frequently in men with ED and hypogonadism, correcting that the sexual problem may require additional methods of treatment.
Nevertheless, correcting the testosterone deficit may have other beneficial effects. These may include increasing energy and well-being, as well as prevention of anemia or bone loss, depending on the severity of the hypogonadism. If patients cannot maintain their testosterone levels in the normal range after clomiphene is discontinued, permanent testosterone replacement with intramuscular injection, transdermal patches, or gels should be considered.
This study had empirical limitations. The relatively small number of patients who received treatment, combined with the low frequencies of many variables of interest, makes it difficult to create a robust logistic regression model. Clearly, an ideal study would match patients on key comorbid and clinical characteristics a priori eg, by type and number of medications, age, past therapy for ED, and lifestyles , and would utilize a placebo-controlled, randomized design.
However, we controlled for confounding variables a posteriori during regression analysis. We also conducted extensive diagnostic analyses before attempting the regression to ensure that variables were included appropriately. Finally, several competing models were compared and all results were similar, suggesting that the model exhibits a reasonable fit to the data. These findings reinforce the recommendation to check testosterone levels in all men with ED.
We also conclude that clomiphene stimulation may provide a reasonable option to correct hypogonadotropic hypogonadism, especially when it is functional in etiology and might be temporary in nature. An example of this scenario is a man with hypogonadism and sleep apnea a very common combination , who may need testosterone therapy while starting a weight loss program and undergoing treatment with positive pressure nocturnal therapy.
Owing to its low profile of side effects, clomiphene can be considered as a safe alternative form of shor t -term testosterone replacement. However, caution should be exercised in certain areas. We recently published our findings concerning testosterone and prostate-specific antigen PSA levels. Therefore, monitoring PSA levels before and after treatment is imperative, even with clomiphene stimulation.
If the level of PSA is elevated before or after the clomiphene, the treatment should be stopped and the patient evaluated by a urologist. We recently had one young man who presented with the complaint of shimmering visual fields while on clomiphene palleanopsia , which cleared after cessation of use. This has been reported in women using clomiphene during fertility treatment.
Finally, this study should be replicated using a matched, randomized, prospective design in the general ED population, to ensure that results are free of ascertainment bias and to control for possible confounding variables during sample selection. Feldman HA et al. Impotence and its medical and psychosocial correlates: J Urol ; Sexual dysfunction in the United States.
Age, disease and changing sex hormone levels in middle-aged men: J Clin Endocrinol Metab ; Deslypere JP , Vermeulen A. Leydig cell function in normal men: