Obesity and Male Infertility Therapeutic Treatments

Obesity and Male Infertility and Therapeutic Suggestions

Cause of male infertility. Obesity are associated with infertility in men in many studies, and the time trend of declining sperm parameters in parallel. The rising prevalence of obesity in the developed world In addition to semen quality, the fertility in obese men to be affected by low libido and erectile dysfunction. This expression hypogonadism in obese men spectrum comes from several interrelated factors such as reduced levels of testosterone and gonadotropin abnormal relationship to estrogen-androgen, insulin resistance, and sleep apnea. There are no evidence-based treatment, which increases the chance of pregnancy for male infertility and obesity has been shown previously. Interventions in relation to the improvement of the intermediate results, including endocrine profile sperm parameters and sexual function can be selected accordingly depending on the history, physical examination, and the endocrine and metabolic evaluation. These interventions include weight loss due to a change of life, to relieve sleep apnea, the use of aromatase inhibitors, gonadotropins, phosphodiesterase inhibitors, and agents of insulin sensitization.

Introduction

Infertility is defined as the absence of a pregnancy after one year of unprotected sexual intercourse defined, 1 concerns in 13 couples in the United States. Male infertility is 25-30% of all cases of infertility and contributes, in combination with female factors, 30%. Recognized causes of male infertility include cryptorchidism, testicular torsion or trauma, varicocele, seminal tract infections, sperm antibodies, hypogonadism, gonadal and reproductive tract obstruction. Adopted in cases of male infertility couples are often intrauterine artificial insemination  (IUIS) offered or in-vitro fertilization (IVF), ICSI (ICSI). These therapies are expensive and can hit out of the reach for many couples.

Therapeutic interventions simple, cheap and effective male infertility are required. Candidates potentially effective interventions include changes in diet and lifestyle changes and can be use in any cause of male infertility. These interventions are gaining importance in view of reports that it increases in parallel with the plush body mass index (BMI), the prevalence of male infertility is on the rise, as the drop is cum all over the world in recent decades. It has been estimated that the number of sperm decreased by 1.5% per year in the United States, a finding that is also found in other Western countries.


Several explanations have been proposed to reduce male fertility, including the increased prevalence of obesity and exposure environmental contamination during fetal or adult life. We know that the prevalence of obesity increases in the United States and abroad. Between 1991 and 1998, the prevalence of obesity has risen from 12 to 17.9% in the general population and 11.7 to 17.9% for men. Hedley et al estimated the current prevalence of obesity of 30.6%. Several reports have described the effect of obesity on male fertility. This effect appears multifactorial and can be modulated by genetic and environmental factors.
Therapeutic suggestions

There are few studies specifically focus on the outcomes of the treatment of infertility in obese men. Therapeutic interventions are described in the next section is designed to the anomalies mentioned in connection with reverse obesity. The assignment of the cause of the poor semen parameters is often difficult. It is reasonable to infertile obese men with poor sperm parameters and without the reasons here, as if their obesity is responsible manage lists.

Changes in weight loss and lifestyle interventions, the effect of lifestyle modification and weight loss of male fertility in the short and long term fat currently unknown. Some studies have reported the effects of weight loss programs or bariatric surgery on the intermediate results of male fertility since. Hormonal profile sperm parameters and sexual function Obese men showed an increase in sex hormone binding globulin and testosterone (free and total) after a very low energy diet. Other studies have shown that weight loss through bariatric surgery was associated with the correction of abnormal hormonal profile in obese men with elevated testosterone and SHBG and reduction of estradiol. In this context, the effect of the weight loss in inhibin B levels as a surrogate of spermatogenesis of particular interest. Globerman et al studied the concentrations of inhibin B after Silastic ring gastroplasty. obese men showed the four men raised in the greatest decrease BMI levels of inhibin. However, the means of inhibin B, before and after gastroplasty is not statistically significant.

In a recent article Håkonsen et al have described the effect of a weight loss program for 14 weeks in the hormonal profile and sperm parameters in obese men (BMI 33-61 kg/m2). The average weight loss was 22 kg. After subanalysis <10 patients with greater weight loss (between 43 men and one third to low sperm, median / range of weight loss: 15%, from 3.5 to 25.4), SHBG an overall increase sperm count (p = 0, 02), semen volume (p = 0.04), testosterone (p = 0.02), (p = 0.03) and anti-Mullerian hormone (p = 0.02) was found. However, it is likely that in addition to the random differences in sperm parameters due to an increase in the volume of the sperm and accessory gland to emissions were, because the sperm concentration was unchanged (p = 0, 33).

It is worth noting that reports associated bariatric surgery with male infertility. In one case described, ie, et al Frega six obese men. With at least one previous child, presented with azoospermia after the Roux-en-Y gastric bypass surgery Subjected Sermondade et al described three male patients, bariatric surgery and subsequently developed trace astheno teratozoospermia. In a case where changes in spermatogenesis reversible 2 years after surgery. This led the authors to the conservation of sperm prior to bariatric surgery in men suggest fertility preservation.

Faced with this alarming anecdotal reports of nine cases showed a prospective randomized study of Rice et al, that the semen parameters are not Brazilian in 20 morbidly obese men change (mean age 11.3 ± 39.3 years, the average weight and BMI: 168.6 ± 28.2 and 55.7 ± 7.8 respectively), for 24 months in an intensive weight loss program followed, 10 were bariatric surgery have reduced the average BMI of 24.7 kg/m2. No patient with semen characteristics the World Health Organization (2010) presented at baseline after bariatric surgery [86] Despite the lifestyle changes simply to BMI (mean reduction of 12.6)., Bariatric surgery first hormonal imbalance and ED, consistent with our study invested an improvement in overall sexual satisfaction scores showed after surgery for weight loss Roux-en-Y gastric bypass. In another randomized study, overweight men, the detailed advice on how to got get a loss of ≥ 10% of their total body weight by reducing caloric intake and increasing their physical activity a higher greater weight loss and improved controls erectile dysfunction.

In the presence of sleep apnea, patients lose weight and improve sleep apnea can also increase your testosterone levels. [88] Grunstein et al have shown that nasal pressure of 3 months continuous positive airway pressure (CPAP) resulted in an increase of total testosterone and SHBG, but not testosterone is free. Luboshitzky et al similar changes nine months after CPAP. Santamaria et al showed that in men with sleep apnea may uvulopalatopharyngoplasty increase testosterone levels without significant changes in BMI.

Conversely Bratel et al found no difference in testosterone levels after 7 months of CPAP. Meston et al conducted a randomized study CPAP therapy or placebo and showed no improvement in testosterone levels after 4 weeks of follow up.The lack of performance in this study could be attributed to the short track.

Aromatase medical therapy The finding of an increased low estradiol and testosterone to estradiol ratio proposed in obese men that aromatase inhibitors may be a potential treatment for infertility in this group. Role of aromatase inhibitors in the treatment of idiopathic male infertility remains controversial. In the context of obese men aromatase inhibitors are proven to improve hypogonadism. Treatment with aromatase inhibitors such as testolactone 1 g per day for 6 weeks [94], letrozole 2.5 mg or 2.5 mg every other day for six weeks, and Arimidex 1 mg for 6 months, has led to an increase in LH and testosterone and estradiol reduction in obese men.

These studies, a small number of participants (<10) with severe obesity (BMI ≥ 40 kg/m2 on average) and fertility performed, with the exception of the study by Roth et al, there was the case of a man who at the age of 29 years pregnant with infertility in a position of having a child of 6 months after treatment was anastrozole.

Two studies investigated the effect of this class of drugs in infertile men with reduced testosterone levels of estrogen are due to the similarity with the observed hormone profile remarkably in obese men.

Pavlovich et al treated 45 men with severe male infertility and decreased testosterone to estradiol values ​​with testolactone 50-100 mg twice daily for 5 months (range: 1-24). After treatment, there was an improvement in the profile of serum testosterone and increasing the ratio of testosterone to estradiol. Semen parameters have been tested in a subgroup of 12 men with oligospermia and azoospermia 12 before and after the treatment, testolactone. Sperm concentration, total sperm count and motility Oligospermia improved, but not in men with azoospermia with low testosterone estradiol ratio.

Shlegel Raman and evaluated the effect of anastrozole 1 mg in hormonal profiles and semen of infertile men after reduction of testosterone to estradiol ratio (testosterone (ng / dL) / estradiol (pg / ml) <10). After an average of 4.7 months of treatment, an improvement in serum testosterone and a decrease in serum estradiol, which increases the testosterone to estradiol observed, and these results were confirmed also defined in the subgroup of obese patients (as a BMI> 35 kg/m2 ). A total of 25 men and 14 Azoospermia Oligospermia had tested his sperm before and after at least 3 months of treatment. Oligospermia in males, there was an increase in semen volume, sperm concentration, motility and velocity after treatment with a decrease in the concentration of estradiol and testosterone increased correlated to estradiol. There was no change in men with azoospermia. Unfortunately, the analysis of the data indicated in the subgroup sperm obese, probably because of the small numbers.

Treatment with gonadotropins in obese men may hypogonadism regardless of the increase in estradiol. When this happens can be expected in the presence of low or normal gonadotropin central hypogonadism be sensitive gonadotropin stimulation. The efficacy of FSH in the treatment of idiopathic male infertility FSH and human chorionic gonadotropin (hCG) in the treatment of idiopathic hypothalamic hypogonadism by numerous studies has been proposed. Little is known about the effect of hCG or FSH / hCG in the treatment of secondary hypogonadism with obesity.

Phosphodiesterase inhibitors and androgen therapy phosphodiesterase (PDE) is. As first-line treatment for erectile dysfunction medicine for lifestyle change The main disadvantages figures are concomitant treatment with nitrates or nitric oxide drugs (including bombs amyl nitrite), patients discouraged where sexual activity is (those with unstable angina, congestive congestive heart failure, recent heart attack) or and patients who are allergic are intolerant to the drug. For patients with erectile dysfunction, sildenafil, the first oral inhibitor of PDE was to be available commercially. Tadalafil and vardenafil are treating two new oral agents for the treatment of erectile dysfunction. PDE inhibitors do not improve libido.

Hypogonadal men with low testosterone levels androgen is often used to treat sexual dysfunction, PDE-resistant, as indicated including decreased libido. However, testosterone treatment in infertile men have an adverse effect on spermatogenesis and fertility. Testosterone can inhibit the secretion of gonadotropins by the negative feedback in the hypothalamic-pituitary axis. Decreased gonadotropin production results testicular testosterone and decreases intratesticular low testosterone says. Indeed, androgens are often used in male contraception.

Although the negative effects of androgens on fertility is known, because of the relatively short time since the start of the oral PDE5 inhibitors, further research should be conducted on a large scale.

Metformin With the recognition of an independent contribution of insulin resistance hypogonadism, studies of the effect of metformin on the hormonal profile and sperm parameters in obese men.

Özata et al examined the effects of a low calorie diet (1200-1400 kcal / day) and metformin (850 mg twice daily) for 3 months in the hormonal profile of obese men with or without diabetes type 2. After the intervention, there was a reduction in total and free testosterone in obese men with diabetes compared to men who had reduced their total number, but not testosterone is free. Obese people without diabetes, the reduction of free testosterone by the increase in sex hormone-binding protein described.


In a recent article, Casulari showed an improvement in the amount of free and total testosterone in men with metabolic syndrome and hypogonadism normogonadal after 4 months of treatment with metformin was 850 mg twice per day.

The two studies described above do not report on semen parameters. Morgante et al investigated the effects of metformin (850 mg three times daily for 6 months). In 45 overweight or obese people with metabolic syndrome. There was described a significant improvement in free and total testosterone, estradiol and decreased sperm concentration, motility and normal morphology after treatment, though. No change of the BMI and waist Most research focuses on the effects of metformin on male fertility required. These studies highlight the role of insulin in the pathophysiology of disorders of the reproductive function in obese men and important new avenues for the treatment to offer in many cause of male infertility.