Supplementation with vitamin D does not increase serum testosterone levels in healthy males. Vitamin D Decreases Serum VEGF Correlating with Clinical Improvement in Vitamin D-Deficient Women with PCOS: A Randomized Placebo-Controlled Trial Endogenous Testosterone and Mortality Due to All Causes, Cardiovascular Disease, and Cancer in Men: European Prospective Investigation Into Cancer in Norfolk (EPIC-Norfolk) Prospective Population Study Vitamin D and Testosterone in Healthy Men: A Randomized Controlled Trial Vitamin D deficiency and low ionized calcium are linked with semen quality and sex steroid levels in infertile men. Correcting vitamin D insufficiency improves insulin sensitivity in obese adolescents: a randomized controlled trial. Rising serum 25-hydroxy-vitamin D levels after weight loss in obese women correlate with improvement in insulin resistance. High-dose vitamin D supplementation and measures of insulin sensitivity in polycystic ovary syndrome: a randomized, controlled pilot trial. Low serum testosterone and mortality in older men. Vitamin D improves endometrial thickness in PCOS women who need intrauterine insemination: a randomized double-blind placebo-controlled trial The Effects of Vitamin D-K-Calcium Co-Supplementation on Endocrine, Inflammation, and Oxidative Stress Biomarkers in Vitamin D-Deficient Women with Polycystic Ovary Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial. Association between plasma 25‐OH vitamin D and testosterone levels in men The level of serum anti-Müllerian hormone correlates with vitamin D status in men and women but not in boys. Vitamin D Supplementation Decreases TGF-β1 Bioavailability in PCOS: A Randomized Placebo-Controlled Trial. Vitamin D Status Relates to Reproductive Outcome in Women With Polycystic Ovary Syndrome: Secondary Analysis of a Multicenter Randomized Controlled Trial. Incidence and main causes of infertility in a resident population (1,850,000) of three French regions (1988-1989). Effect of vitamin D supplementation on testosterone levels in men.
Cross-sectional studies indicate a positive relation between serum 25-hydroxyvitamin D [ 25(OH)D ] and testosterone . It is not known if this relation is causal , which in theory could be in both directions . A cross-sectional population based study was design ed with pooled data from 3 vitamin D r and omized clinical trials ( RCTs ) performed in Tromsø with weight reduction , insulin sensitivity , and depression scores as endpoints , and one  testosterone RCT in subjects with low serum testosterone ( < 11.0 nmol/l ) and with body composition as endpoint .  Serum 25(OH)D and and rogens were measured in 893 males in the cross-sectional part , at baseline and after 6 - 12 months of supplementation with vitamin D 20 000 IU-40 000 IU per week vs. placebo in the vitamin D RCTs ( n=282 ) , and at baseline and after one year treatment with testosterone undecanoate 1 000 mg or placebo injections ( at baseline and after 6 , 16 , 28 , and 40 weeks ) in the testosterone RCT ( n=37 ) . In the cross-sectional study , serum 25(OH)D was found to be a significant and positive predictor of serum testosterone . In the vitamin D RCTs , no significant effect on serum total or free testosterone levels was seen , and in the testosterone RCT no significant effect on serum 25(OH)D was seen . This was unchanged in sub-analyses in subjects with low serum 25(OH)D ( or testosterone ) levels . In conclusion , in subjects without significant vitamin D deficiency , there is no increase in serum testosterone after high dose vitamin D supplementation . Similarly , in subjects with moderately low serum testosterone levels  , substitution with testosterone does not increase serum Vascular endothelial growth factor ( VEGF ) has been suggested to play a role in the pathophysiology of polycystic ovary syndrome ( PCOS ) and may contribute to increased risk of ovarian hyperstimulation syndrome ( OHSS ) in affected individuals .  Vitamin D ( VitD ) supplementation improves multiple clinical parameters in VitD-deficient women with PCOS and decreases VEGF levels in several other pathologic conditions . Unveiling the basic mechanisms underlying the beneficial effects of vitamin D on PCOS may enhance our underst and ing of the pathophysiology of this syndrome . It may also suggest a new treatment for PCOS that can improve it through the same mechanism as vitamin D and can be given regardless of vitamin D levels . Therefore , we aim ed to explore the effect of VitD supplementation on serum VEGF levels and assess whether changes in VEGF correlate with an improvement in characteristic clinical abnormalities of PCOS . This is a r and omized placebo-controlled trial conducted between October 2013 and March 2015 . Sixty-eight VitD-deficient women with PCOS were recruited . Women received either 50,000 IU of oral VitD3 or placebo once weekly for 8 weeks . There was a significant decrease in serum VEGF levels ( 1106.4 ± 36.5 to 965.3 ± 42.7 pg·mL–1 ; p < 0.001 ) in the VitD group . Previously reported findings of this trial demonstrated a significant decrease in the intermenstrual intervals , Ferriman-Gallwey hirsutism score , and triglycerides  following VitD supplementation . Interestingly , ∆VEGF was positively correlated with ∆triglycerides ( R2 = 0.22 ; p = 0.02 ) following VitD supplementation . In conclusion , VitD replacement significantly decreases serum VEGF levels correlating with a decrease in triglycerides in women with PCOS . This is a novel molecular explanation for the beneficial effects of VitD treatment . It also suggests the need to investigate a potential role of VitD treatment in reducing the incidence or severity of OHSS in VitD-deficient women with PCOS Background — The relation between endogenous testosterone concentrations and health in men is controversial . Methods and Results — We examined the prospect i ve relationship between endogenous testosterone concentrations and mortality due to all causes , cardiovascular disease , and cancer in a nested case-control study based on 11 606 men aged 40 to 79 years surveyed in 1993 to 1997 and followed up to 2003 . Among those without prevalent cancer or cardiovascular disease , 825 men who subsequently died were compared with a control group of 1489 men still alive , matched for age and date of baseline visit .  Endogenous testosterone concentrations at baseline were inversely related to mortality due to all causes ( 825 deaths ) , cardiovascular disease ( 369 deaths ) , and cancer ( 304 deaths ) . Odds ratios ( 95 % confidence intervals ) for mortality for increasing quartiles of endogenous testosterone compared with the lowest quartile were 0.75 ( 0.55 to 1.00 ) , 0.62 ( 0.45 to 0.84 ) , and 0.59 ( 0.42 to 0.85 ) , respectively ( P<0.001 for trend after adjustment for age , date of visit , body mass index , systolic blood pressure , blood cholesterol , cigarette smoking , diabetes mellitus , alcohol intake , physical activity , social class , education , dehydroepi and rosterone sulfate , and rostanediol glucuronide , and sex hormone binding globulin ) . An increase of 6 nmol/L serum testosterone ( ≈1 SD ) was associated with a 0.81 ( 95 % confidence interval 0.71 to 0.92 , P<0.01 ) multivariable-adjusted odds ratio for mortality . Inverse relationships were also observed for deaths due to cardiovascular causes and cancer and after the exclusion of deaths that occurred in the first 2 years . Conclusions — In men  , endogenous testosterone concentrations are inversely related to mortality due to cardiovascular disease and all causes . Low testosterone may be a predictive marker for those at high risk of cardiovascular disease Context : Available evidence shows an association of vitamin D with and rogen levels in men . However , results from preliminary r and omized controlled trials ( RCTs ) are conflicting . Objective : To evaluate whether vitamin D supplementation increases total testosterone ( TT ) levels in healthy men . Design : The Graz Vitamin D&TT‐ RCT is a single‐center , double‐blind , r and omized , placebo‐controlled trial conducted between December 2012 and January 2017 . Setting : Endocrine outpatient clinic at the Medical University of Graz , Austria . Participants : Ninety‐eight healthy men with TT levels ≥10.4 nmol/L and 25‐hydroxyvitamin D [ 25(OH)D ] levels < 75 nmol/L completed the study . Intervention : Subjects were r and omly assigned to receive 20,000 IU/wk of vitamin D3 ( n = 50 ) or placebo ( n = 50 ) for 12 weeks . Main Outcome Measures : Primary outcome was TT measured using mass spectrometry . Secondary outcomes were free testosterone , sex hormone‐binding globulin , estradiol , follicle‐stimulating hormone , and luteinizing hormone levels ; free and rogen index ; metabolic characteristics ; and body composition . Results : In healthy men [ mean values ± st and ard deviation : age , 39 years ( ±13 years ) ; 25(OH)D level , 53.3 nmol/L ( ±18.3 nmol/L ) ; TT , 19.1 nmol/L ( ±5.6 nmol/l ) ] , no significant treatment effect on TT was found ; however , there were significant effects on quantitative insulin sensitivity check index ( QUICKI ) and a trend toward decreased Matsuda index . In the treatment group , median ( interquartile range ) changes for TT , QUICKI , and Matsuda index were 0.5 nmol/L ( −0.63 to 0.63 nmol/L ; P = 0.497 ) , −0.02 ( −0.04 to 0.01 ; P = 0.034 ) , and −0.9 ( −3.2 to 0.8 ; P = 0.051 ) , respectively . Conclusion : Vitamin D treatment had no effect on TT levels in middle‐aged healthy men with normal baseline TT , but it significantly decreased QUICKI . Additional studies investigating vitamin D effects on TT and insulin sensitivity in healthy men are required STUDY QUESTION Are low vitamin D levels linked with semen quality and sex steroids in infertile men ? SUMMARY ANSWER Infertile men with vitamin D deficiency had lower sperm motility , total numbers of motile sperm , Inhibin B , sex-hormone-binding-globulin ( SHBG ) and testosterone/estradiol ratio , but higher levels of free sex steroids , than infertile men with normal vitamin D levels . WHAT IS KNOWN ALREADY Low vitamin D levels have been associated with decreased sperm motility in healthy men , but a relationship between vitamin D and calcium with semen quality and especially sex steroids has not been sufficiently described in infertile men . STUDY DESIGN , SIZE , DURATION This study comprises baseline characteristics of 1427 infertile men screened from 2011 to 2014 for inclusion in a r and omized clinical trial , the Copenhagen-Bone-Gonadal Study . PARTICIPANTS / MATERIAL S , SETTING , METHODS In total 1427 infertile men , consecutively referred to our tertiary and rological centre for fertility workup , underwent a physical examination and had semen quality assessed based on two sample s and blood analysed for serum testosterone , SHBG , estradiol , inhibin B , luteinizing hormone , follicle-stimulating hormone ( FSH ) , 25-hydroxyvitamin D ( 25-OHD ) , ionized calcium ( Ca(2 + ) ) and karyotype . There were 179 men excluded due to serious comorbidities or anabolic steroid usage , leaving 1248 patients for analyses . MAIN RESULTS AND THE ROLE OF CHANCE Men with 25-OHD > 75 nmol/l had higher sperm motility and 66 and 111 % higher total numbers of motile spermatozoa after 45 and 262 min , respectively , than men with 25-OHD < 25 nmol/l ( all P < 0.05 ) . SHBG levels and testosterone/estradiol ratios were 15 and 14 % lower , respectively , while free testosterone and estradiol ratios were 6 and 13 % higher , respectively , in men with 25-OHD < 25 nmol/l ( all P < 0.05 ) . Men with lower Ca(2 + ) levels had higher progressive sperm motility and inhibin B/FSH ratio but lower testosterone/estradiol ratio ( all P < 0.05 ) . LIMITATIONS , REASONS FOR CAUTION All outcomes presented are predefined end-points but inferral of causality is compromised by the descriptive study design . It remains to be shown whether the links between vitamin D , calcium , semen quality and sex steroids in infertile men are causal . WIDER IMPLICATION S OF THE FINDINGS The associations between vitamin D deficiency and low calcium with semen quality and sex steroids support the existence of a cross-link between regulators of calcium homeostasis and gonadal function in infertile men . STUDY FUNDING /COMPETING INTERESTS This study was supported by the Danish Agency for Science , Technology and Innovation , Hørslev Fonden , Danish Cancer Society and Novo Nordisk Foundation . There are no conflicts of interest . TRIAL REGISTRATION NUMBER NCT01304927 . DATE OF TRIAL REGISTRATION 25 February 2011 . DATE OF ENROLMENT OF FIRST PATIENT 8 March 2011 BACKGROUND Obese adolescents are at a greater risk of vitamin D deficiency because vitamin D is thought to be sequestered by excess adipose tissue . Poor vitamin D status has been associated with a higher prevalence of the metabolic syndrome , type 2 diabetes , or both in adults and adolescents . OBJECTIVE The objective was to determine in obese adolescents the efficacy and safety of 4000 IU vitamin D3/d and whether subsequent increased circulating concentrations of 25-hydroxyvitamin D [ 25(OH)D ] are associated with improved markers of insulin sensitivity and resistance and reduced inflammation . DESIGN Obese adolescent patients [ n = 35 ; mean ± SD age : 14.1 ± 2.8 y ; BMI ( in kg/m(2 ) ) : 39.8 ± 6.1 ; 25(OH)D : 19.6 ± 7.1 ng/mL ] were recruited from the University of Missouri Adolescent Diabetes and Obesity Clinic and were r and omly assigned to receive either vitamin D3 ( 4000 IU/d ) or placebo as part of their st and ard care . Anthropometric measurements , inflammatory markers ( IL-6 , TNF-α , C-reactive protein ) , adipokines ( leptin , adiponectin ) , fasting glucose , fasting insulin , and HOMA-IR values were measured at baseline and at 2 follow-up visits ( 3 and 6 mo ) . RESULTS After 6 mo , there were no significant differences in BMI , serum inflammatory markers , or plasma glucose concentrations between groups . Participants supplemented with vitamin D3 had increases in serum 25(OH)D concentrations ( 19.5 compared with 2.8 ng/mL for placebo ; P < 0.001 ) , fasting insulin ( -6.5 compared with + 1.2 μU/mL for placebo ; P = 0.026 ) , HOMA-IR ( -1.363 compared with + 0.27 for placebo ; P = 0.033 ) , and leptin-to-adiponectin ratio ( -1.41 compared with + 0.10 for placebo ; P = 0.045 ) . Inflammatory markers remained unchanged . CONCLUSION The correction of poor vitamin D status through dietary supplementation may be an effective addition to the st and ard treatment of obesity and its associated insulin resistance . This trial was registered at clinical trials.gov as NCT00994396 OBJECTIVE The objective of the study was to examine changes of 25-hydroxy-vitamin D ( 25OHD ) and PTH blood levels 4 and 20 wk after low-calorie diet-induced weight loss . METHODS Forty-four obese women [ aged 40.6 + /- 11.4 yr , body mass index ( BMI ) 36.7 + /- 4.9 kg/m(2 ) ] and 25 controls ( BMI 22.9 + /- 1.5 kg/m(2 ) ) were examined .  Anthropometric and cardiometabolic parameters and 25OHD and PTH levels  were determined at baseline and 4 and 20 wk after a low-calorie diet . RESULTS At baseline , 25OHD levels were lower in obese compared with control subjects ( 17 + /- 6.0 vs. 23.8 + /- 8.7 ng/ml , P < 0.001 ) , whereas no differences were found in PTH levels . In all women , a negative correlation was found between 25OHD levels and body weight ( BW ) ( r -0.32 , P < 0.001 ) , BMI ( r -0.37 , P < 0.001 ) , waist circumference ( r -0.26 , P < 0.05 ) , and percent fat mass ( r -0.38 , P = 0.001 ) as determined by bioelectrical impedance analysis . The 4-wk low-calorie diet ( n = 37 ) reduced BW and led to significant improvements in the homeostasis model assessment ( HOMA ) index and lipid levels . The 20-wk low-calorie diet ( n = 26 ) result ed in reduction of BW and BMI by 10 % , HOMA index ( 4.7 + /- 3.8 vs. 3.10 + /- 1.7 , P < 0.01 ) , and lipids levels ( except high density lipoprotein cholesterol ) and increase in 25OHD ( 15.4 + /- 6.0 vs. 18.3 + /- 5.1 ng/ml , P < 0.05 ) , compared with baseline . PTH levels were unchanged . The increase of 25OHD levels was associated with the reduction of insulin levels and HOMA index ( r -0.43 , P < 0.05 ) . CONCLUSIONS Blood 25OHD levels were low in obese women and correlated inversely with severity measures of obesity . Weight loss of 10 % after low-calorie diet increased 25OHD levels , and this increase was mainly associated with improvement of insulin resistance OBJECTIVE To determine the effects of high-dose vitamin D on insulin sensitivity in polycystic ovary syndrome ( PCOS ) . DESIGN R and omized , placebo-controlled trial . SETTING Academic medical center . PATIENT(S ) Twenty-eight women with PCOS . INTERVENTION(S ) Vitamin D3 , 12,000 IU , or placebo daily for 12 weeks . MAIN OUTCOME MEASURE(S ) The primary outcome was quantitative insulin sensitivity check index . Secondary outcomes included glucose and insulin levels during a 75-g oral glucose tolerance test and blood pressure . RESULT ( S ) Twenty-two women completed the study . Compared with placebo , vitamin D significantly increased 25-hydroxyvitamin D ( mean [ 95 % confidence interval ] in vitamin D group 20.1 [ 15.7 to 24.5 ] ng/mL at baseline and 65.7 [ 52.3 to 79.2 ] ng/mL at 12 weeks ; placebo 22.5 [ 18.1 to 26.8 ] ng/mL at baseline and 23.8 [ 10.4 to 37.2 ] ng/mL at 12 weeks ) . There were no significant differences in quantitative insulin sensitivity check index and other measures of insulin sensitivity ; however , we observed trends toward lower 2-hour insulin and lower 2-hour glucose . We also observed a protective effect of vitamin D on blood pressure . CONCLUSION ( S ) In women with PCOS , insulin sensitivity was unchanged with high-dose vitamin D , but there was a trend toward decreased 2-hour insulin and a protective effect on blood pressure . CLINICAL TRIAL REGISTRATION NUMBER NCT00907153 CONTEXT Declining testosterone levels in elderly men are thought to underlie many of the symptoms and diseases of aging ; however , studies demonstrating associations of low testosterone with clinical outcomes are few . OBJECTIVE The objective of the study was to examine the association of endogenous testosterone levels with mortality in older community-dwelling men . DESIGN , SETTING , AND PARTICIPANTS This was a prospect i ve , population -based study of 794 men , aged 50 - 91 ( median 73.6 ) yr who had serum testosterone measurements at baseline ( 1984 - 1987 ) and were followed for mortality through July 2004 . MAIN OUTCOME MEASURE All-cause mortality by serum testosterone level  was measured . RESULTS During an average 11.8-yr follow-up , 538 deaths occurred . Men whose total testosterone levels were in the lowest quartile ( < 241 ng/dl ) were 40 % [ hazards ratio ( HR ) 1.40 ; 95 % confidence interval ( CI ) 1.14 - 1.71 ] more likely to die than those with higher levels , independent of age , adiposity , and lifestyle . Additional adjustment for health status markers , lipids , lipoproteins , blood pressure , glycemia , adipocytokines , and estradiol levels had minimal effect on results . The low testosterone-mortality association was also independent of the metabolic syndrome , diabetes , and prevalent cardiovascular disease but was attenuated by adjustment for IL-6 and C-reactive protein . In cause-specific analyses , low testosterone predicted increased risk of cardiovascular ( HR 1.38 ; 95 % CI 1.02 - 1.85 ) and respiratory disease ( HR 2.29 ; 95 % CI 1.25 - 4.20 ) mortality but was not significantly related to cancer death ( HR 1.34 ; 95 % CI 0.89 - 2.00 ) . Results were similar for bioavailable testosterone . CONCLUSIONS Testosterone insufficiency in older men is associated with increased risk of death over the following 20 yr , independent of multiple risk factors and several preexisting health conditions Abstract Purpose To determine whether administration of vitamin D affects the success rates of intra uterine insemination  ( IUI ) in infertile polycystic ovarian syndrome ( PCOS ) women and their endometrial thickness . Methods This r and omized , double-blind , placebo-controlled trial was conducted in an infertility clinic of Women ’s Hospital , and 110 infertile PCOS patients undergoing IUI were r and omly divided to receive vitamin D or placebo .  Endometrial thickness , IUI results , number of dominant follicles , duration of IUI cycle , and dose of HMG used in IUI were determined . Results The endometrial thickness was significantly different in the group treated with vitamin D versus the placebo group ( p = 0.003 ) . There was no statistical difference in pregnancy out come between the two groups ( RR = 1.167 , CI 95 % 0.70–1.93 ) . No statistical difference was found in number of dominant follicles ( p = 0.96 ) , duration of IUI cycles ( p = 0.70 ) and dose of HMG used for IUI ( p = 0.95 ) . Conclusions It seems that administration of vitamin D induces endometrial proliferation in PCOS women during IUI cycle The current study was conducted to assess the effects of vitamin D-K-calcium co-supplementation on endocrine , inflammation , and oxidative stress biomarkers in vitamin D-deficient women with polycystic ovary syndrome ( PCOS ) . This r and omized double-blind , placebo-controlled trial was performed on 60 vitamin D-deficient women diagnosed with PCOS aged 18 - 40 years old . Participants were r and omly allocated into 2 groups to intake either 200 IU vitamin D , 90 μg vitamin K plus , 500 mg calcium supplements ( n=30 ) , or placebo ( n=30 ) twice a day for 8 weeks . Endocrine , inflammation , and oxidative stress biomarkers were quantified at the beginning and the end of the study . After 8 weeks of intervention , compared with the placebo , vitamin D-K-calcium co-supplementation result ed in a significant reduction in serum-free testosterone ( - 2.1±1.6 vs.+0.1±1.0 pg/ml , p<0.001 ) and dehydroepi and rosterone sulfate ( DHEAS ) levels ( - 0.8±1.0 vs.-0.1±0.5 μg/ml , p=0.006 ) . In addition , a significant increase in plasma total antioxidant capacity ( TAC ) ( + 75.7±126.1 vs.-80.4±242.8 mmol/l , p=0.005 ) and a significant difference in plasma malondialdehyde ( MDA ) concentrations ( + 0.03±0.6 vs.+1.4±2.4 μmol/l , p=0.005 ) was observed following the supplementation with vitamin D-K-calcium compared with the placebo . A trend toward a greater decrease in luteinizing hormone was observed in vitamin D-K-calcium co-supplement group compared to placebo group ( - 7.0 vs.-1.2 IU/l , p=0.09 ) . We did not find any significant effect of vitamin D-K-calcium co-supplementation  on prolactin , follicle-stimulating hormone , 17-OH progesterone , inflammatory markers , and glutathione levels . Overall , vitamin D-K-calcium co-supplementation for 8 weeks among vitamin D-deficient women with PCOS had beneficial effects on serum DHEAS , free testosterone , plasma TAC , and MDA levels Objective A small r and omized controlled trial suggested that vitamin D might increase the production of testosterone in men , which is supported by experimental studies in animals and a cross‐sectional study showing positive associations between plasma 25‐hydroxyvitamin D [ 25(OH)D ] and testosterone and concordant seasonal variation of both biomarkers CONTEXT Anti-Müllerian hormone ( AMH ) is a gonad-specific hormone , which is extensively used as a marker of gonadal status . The level of serum AMH has a high variance in similar individuals for reasons that are unknown . The AMH gene promoter contains a vitamin D response element that may cause vitamin D status to influence serum AMH levels . AIM The objective of the study was to determine whether serum levels of AMH are related to 25-hydroxyitamin D [ 25(OH)D ) ] status . SETTING This was a correlative and intervention study . PARTICIPANTS Three cohorts of participants were analyzed ; mature men ( n = 113 ) , premenopausal women ( n = 33 ) , and 5- to 6-yr-old boys ( n = 74 ) . Women were given a daily supplement of ergocalciferol , cholecalciferol , or a placebo for 6 months and provided baseline and posttreatment blood sample s. MAIN OUTCOME MEASURES Serum AMH and 25(OH)D were measured and analyzed for covariation . RESULTS Serum AMH positively correlated with 25(OH)D in men ( r = 0.22 , P = 0.02 ) but not boys . Both 25(OH)D and AMH levels exhibited seasonal variation in women , with an 18 % decrease in AMH levels in winter compared with summer ( P = 0.01 ) . Change in AMH level correlated with the initial AMH level and the magnitude of change in vitamin D levels ( r = 0.36 , P = 0.004 ) . Cholecalciferol supplementation prevented seasonal AMH change . CONCLUSION Vitamin D may be a positive regulator of AMH production in adults , and vitamin D deficiency may confound clinical decisions based on AMH . Vitamin D deficiency should be considered when serum AMH levels are obtained for diagnosis CONTEXT There is an abnormal increase in TGF-β1 bioavailability in women with polycystic ovary syndrome ( PCOS ) , which might play a role in the pathophysiology of this syndrome . Vitamin D ( VD ) supplementation improves various clinical manifestations of PCOS and decreases TGF-β1 levels in several diseases including myelofibrosis . OBJECTIVE The objective of the study was to determine the effect of VD supplementation on TGF-β1 bioavailability in VD-deficient women with PCOS and assess whether changes in TGF-β1/soluble endoglin ( sENG ) levels correlate with an improvement in PCOS clinical manifestations . DESIGN This was a prospect i ve , r and omized , placebo-controlled trial . SETTING The study was conducted at an academic-affiliated medical center . PARTICIPANTS Sixty-eight VD-deficient women with PCOS who were not pregnant or taking any exogenous hormones were recruited between October 2013 and January 2015 . INTERVENTIONS Forty-five women received 50 000 IU of oral vitamin D3 and 23 women received oral placebo once weekly for 8 weeks . MAIN OUTCOMES MEASURES Serum TGF-β1 , sENG , lipid profile , testosterone , dehydroepi and rosterone sulfate , and insulin resistance were measured . The clinical parameters were evaluated before and 2 months after treatment . RESULTS The VD level significantly increased and normalized after VD supplementation ( 16.3 ± 0.9 [ SEM ] to 43.2 ± 2.4 ng/mL ; P < .01 ) , whereas it did not significantly change after placebo . After the VD supplementation , there was a significant decrease in the following : the interval between menstrual periods ( 80 ± 9 to 60 ± 6 d ; P = .04 ) , Ferriman-Gallwey score ( 9.8 ± 1.5 to 8.1 ± 1.5 ; P < .01 ) , triglycerides ( 138 ± 22 to 117 ± 20 mg/dL ; P = .03 ) , and TGF-β1 to sENG ratio ( 6.7 ± 0.4 to 5.9 ± 0.4 ; P = .04 ) . In addition , the ΔTGF-β1 to sENG ratio was positively correlated with Δtriglycerides ( r = 0.59 ; P = .03 ) . CONCLUSIONS VD supplementation in VD-deficient women with PCOS significantly decreases the bioavailability of TGF-β1 , which correlates with an improvement in some abnormal clinical parameters associated with PCOS . This is a novel mechanism that could explain the beneficial effects of VD supplementation in women with PCOS . These findings may support new treatment modalities for PCOS , such as the development of anti-TGF-β drugs CONTEXT Experimental evidence supports a relevance of vitamin D ( VitD ) for reproduction ; however , data in humans are sparse and inconsistent . OBJECTIVE To assess the relationship of VitD status with ovulation induction ( OI ) outcomes in women with polycystic ovary syndrome ( PCOS ) . DESIGN A retrospective cohort . SETTING Secondary analysis of r and omized controlled trial data . PARTICIPANTS Participants in the Pregnancy in PCOS I ( PPCOS I ) r and omized controlled trial ( n = 540 ) met the National Institutes of Health diagnostic criteria for PCOS . INTERVENTIONS  Serum 25OHD levels were measured in stored sera . MAIN OUTCOME MEASURES Primary , live birth ( LB ) ; secondary , ovulation and pregnancy loss after OI . RESULTS Likelihood for LB was reduced by 44 % for women if the 25OHD level was < 30 ng/mL ( < 75 nmol/L ; odds ratio [ OR ] , 0.58 [ 0.35 - 0.92 ] ) . Progressive improvement in the odds for LB was noted at thresholds of ≥38 ng/mL ( ≥95 nmol/L ; OR , 1.42 [ 1.08 - 1.8 ] ) , ≥40 ng/mL ( ≥100 nmol/L ; OR , 1.51 [ 1.05 - 2.17 ] ) , and ≥45 ng/mL ( ≥112.5 nmol/L ; OR , 4.46 [ 1.27 - 15.72 ] ) . On adjusted analyses , VitD status was an independent predictor of LB and ovulation after OI . CONCLUSIONS In women with PCOS , serum 25OHD was an independent predictor of measures of reproductive success after OI . Our data identify reproductive thresholds for serum 25OHD that are higher than recommended for the nonpregnant population To estimate the prevalence and main causes of infertility , a multicentre survey was conducted over 1 year ( July 1988-June 1989 ) in three regions of France . All the 1686 couples in these regions , who consulted a practitioner for primary or secondary infertility during this period , were included in the investigation . The prevalence rate of infertility was found to be 14.1 % , indicating that one woman out of seven in France will consult a doctor for an infertility problem during her reproductive life . The main causes of female infertility were ovulation disorders ( 32 % ) and tubal damage ( 26 % ) , and of male infertility oligo-terato-asthenozoospermia ( 21 % ) , asthenozoospermia ( 17 % ) , teratozoospermia ( 10 % ) and azoospermia ( 9 % ) . Infertility was also found to be caused by disorders in both the male and female partners together ; thus in 39 % of cases both the man and woman presented with disorders . The woman alone was responsible for infertility in one-third of cases and the man alone in one-fifth . Unexplained infertility was found in 8 % of the couples surveyed The male reproductive tract has been identified as a target tissue for vitamin D , and previous data suggest an association of 25-hydroxyvitamin D [ 25(OH)D ] with testosterone levels in men . We therefore aim ed to evaluate whether vitamin D supplementation influences testosterone levels in men . Healthy overweight men undergoing a weight reduction program who participated in a r and omized controlled trial were analyzed for testosterone levels . The entire study included 200 nondiabetic subjects , of whom 165 participants ( 54 men ) completed the trial . Participants received either 83 μg ( 3,332 IU ) vitamin D daily for 1 year ( n = 31 ) or placebo ( n = 2 3 ) . Initial 25(OH)D concentrations were in the deficiency range ( < 50 nmol/l ) and testosterone values were at the lower end of the reference range ( 9.09 - 55.28 nmol/l for males aged 20 - 49 years ) in both groups . Mean circulating 25(OH)D concentrations increased significantly by 53.5 nmol/l in the vitamin D group , but remained almost constant in the placebo group . Compared to baseline values , a significant increase in total testosterone levels ( from 10.7 ± 3.9 nmol/l to 13.4 ± 4.7 nmol/l ; p < 0.001 ) , bioactive testosterone ( from 5.21 ± 1.87 nmol/l to 6.25 ± 2.01 nmol/l ; p = 0.001 ) , and free testosterone levels ( from 0.222 ± 0.080 nmol/l to 0.267 ± 0.087 nmol/l ; p = 0.001 ) were observed in the vitamin D supplemented group . By contrast , there was no significant change in any testosterone measure in the placebo group . Our results suggest that vitamin D supplementation might increase testosterone levels . Further r and omized controlled trials are warranted to confirm this hypothesis
BACKGROUND Accumulating evidence from animal and human studies suggests that vitamin D is involved in many functions of the reproductive system in both genders .
AIM The aim of this review was to provide an overview on the effects of vitamin D on polycystic ovary syndrome ( PCOS ) in women and and rogen metabolism in men .
RESULTS AND DISCUSSION The vitamin D receptor and vitamin D-metabolizing enzymes are found in reproductive tissues of women and men .
In women ,  vitamin D status has been associated with several features of PCOS .