Background: Vitamin D has been well-known for its function in maintaining calcium and phosphorus homeostasis and promoting bone mineralization. There is some evidence that in addition to sex steroid hormones, the classic regulators of human reproduction, vitamin D also modulates reproductive processes in women and men. Aim: The aim of this review was to assess the studies that evaluated the relationship between vitamin D and fertility in women and men as well as in animals. Methods: We performed a systematic literature search in Pubmed for relevant English language publications published until October 2011. Results and discussion: The vitamin D receptor (VDR) and vitamin D metabolizing enzymes are found in reproductive tissues of women and men. Vdr knockout mice have significant gonadal insufficiency, decreased sperm count and motility, and histological abnormalities of testis, ovary and uterus. Moreover, we present evidence that vitamin D is involved in female reproduction including IVF outcome (clinical pregnancy rates) and polycystic ovary syndrome (PCOS). In PCOS women, low 25-hydroxyvitamin D (25(OH)D) levels are associated with obesity, metabolic, and endocrine disturbances and vitamin D supplementation might improve menstrual frequency and metabolic disturbances in those women. Moreover, vitamin D might influence steroidogenesis of sex hormones (estradiol and progesterone) in healthy women and high 25(OH)D levels might be associated with endometriosis. In men, vitamin D is positively associated with semen quality and androgen status. Moreover, vitamin D treatment might increase testosterone levels. Testiculopathic men show low CYP21R expression, low 25(OH)D levels, and osteoporosis despite normal testosterone levels.

Androgen levels and 25(OH)D levels are associated in men and reveal a concordant seasonal variation. Randomized controlled trials are warranted to evaluate the effect of vitamin D supplementation on androgen levels.

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 aimed to evaluate whether vitamin D supplementation influences testosterone levels in men. Healthy overweight men undergoing a weight reduction program who participated in a randomized 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 randomized controlled trials are warranted to confirm this hypothesis.

Introduction: Women with polycystic ovary syndrome (PCOS) frequently suffer from metabolic disturbances including insulin resistance (IR), which might be related to vitamin D metabolism. We aimed to investigate the association of polymorphisms in the vitamin D receptor (VDR) gene as well as vitamin D level-associated genes with metabolic and endocrine parameters in PCOS women. Moreover, we examined whether there are associations with PCOS susceptibility. Methods: Metabolic, endocrine, and anthropometric measurements and oral glucose tolerance tests were performed in 545 PCOS and 145 control women. Genotyping of VDR (Cdx2, Bsm-I, Fok-I, Apa-I, and Taq-I), GC, DHCR7, and CYP2R1 polymorphisms was performed. Results: 25-Hydroxyvitamin D (25(OH)D) levels showed significant negative correlation with IR and positive correlation with insulin sensitivity (P!0.05 for all) in PCOS women. In PCOS women, the VDR Cdx2 ' AA' genotype was associated with lower fasting insulin (PZ0.039) and homeostatic model assessment-IR (PZ0.041) and higher quantitative insulin-sensitivity check index (PZ0.012) and MATSUDA index (PZ0.003). The VDR Apa-I ' AA' genotype was associated with lower testosterone (PZ0.028) levels. In PCOS women, 170 women (31.2%) presented with 25(OH)D levels !20 ng/ml. PCOS women carrying the GC 'GG' genotype and the DHCR7 'GG' genotype had a significantly higher risk for 25(OH)D levels !20 ng/ml (OR 2.53 (1.27-5.06), PZ0.009, and OR 2.66 (1.08-6.55), PZ0.033 respectively) compared with PCOS women carrying the GC 'TT' genotype and DHCR 'TT' genotype in multivariate analyses. We observed no association of genetic variations and PCOS susceptibility. Conclusion: VDR and vitamin D level-related variants are associated with metabolic and endocrine parameters including 25(OH)D levels in PCOS women.

Acne, one of the most common skin disorders, is also a cardinal component of many systemic diseases or syndromes. Their association illustrates the nature of these diseases and is indicative of the pathogenesis of acne. Congenital adrenal hyperplasia (CAH) and seborrhoea-acne-hirsutism-androgenetic alopecia (SAHA) syndrome highlight the role of androgen steroids, while polycystic ovary (PCO) and hyperandrogenism-insulin resistance-acanthosis nigricans (HAIR-AN) syndromes indicate insulin resistance in acne. Apert syndrome with increased fibroblast growth factor receptor 2 (FGFR2) signalling results in follicular hyperkeratinization and sebaceous gland hypertrophy in acne. Synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO) and pyogenic arthritis-pyoderma gangrenosum-acne (PAPA) syndromes highlight the attributes of inflammation to acne formation. Advances in the understanding of the manifestation and molecular mechanisms of these syndromes will help to clarify acne pathogenesis and develop novel therapeutic modalities.

Based on the observation that diabetes, obesity, and hypogonadism influence bone metabolism, the existence of a feedback loop and a common regulation was postulated and an endocrine role ascribed to the skeleton. In the first part of this review, two pathways are described whereby adipose tissue acts on bone mass. In the first, leptin activates the sympathetic nervous system via serotonin and diminishes bone mass accrual. The second pathway functions via the activation of CART (CARTPT) and inhibits bone resorption. The first pathway leads to a decrease in bioactivity of the osteoblast-produced hormone osteocalcin (OC) (part 2). In its undercarboxylated form, OC acts on the three targets pancreas, adipose tissue, and gonads (part 3) and thereby causes an increase in insulin secretion and sensitivity, b-cell proliferation, and male fertility. Insulin (part 4) is part of a recently discovered regulatory feedback loop between pancreas and osteoblasts. It is a strong counterplayer of leptin as it causes a decrease in OPG expression and enhances bone resorption and OC decarboxylation. Numerous clinical studies (part 5) have shown associations of total and undercarboxylated OC and markers of energy metabolism. Interventional studies, to date only performed in murine models, have shown positive effects of OC administration on energy metabolism. Whether bone tissue has an even further-reaching endocrine role remains to be elucidated. European Journal of Endocrinology 166 959-967

Our data provide evidence for a strong link between a high TT/DHT ratio and an adverse metabolic phenotype in PCOS patients. This correlation was only found in PCOS patients, suggesting the TT/DHT ratio to be a new biomarker for an adverse metabolic phenotype in PCOS patients.

In a recent genome-wide association study investigating Han Chinese PCOS women 3 loci that are strongly associated with PCOS were identified on chromosome 2p16.3 (rs13405728), 2p21 (rs13429458), and 9q33.3 (rs2479106). The aim of the study was to investigate the impact of rs13405728, rs13429458, and rs2479106 variants on PCOS susceptibility in a Caucasian cohort of PCOS and control women. Metabolic, endocrine, and anthropometric measurements and oral glucose tolerance tests were performed in 545 PCOS and 317 control women. The rs13405728, rs13429458, and rs2479106 polymorphisms were genotyped. There was no significant difference in genotype frequencies of rs13405728 and rs13429458 variants between PCOS and controls. There was a trend towards an association of the rs2479106 variant with PCOS susceptibility (p=0.053). PCOS women with the rs2479106 GG genotype had significantly higher WHR than PCOS women carrying the AG and AA genotype (p=0.034 and p=0.020, respectively). Moreover, QChol/HDL and LDL levels were significantly higher in PCOS women carrying the rs2479106 GG genotype when compared to those carrying the AA genotype (p=0.024 and p=0.035, respectively). PCOS women carrying the G allele of rs13405728 had significantly higher AUCgluc, glucose-30 min, and AUCins levels than those carrying the AA genotype (p=0.039, p=0.047, and p=0.044, respectively). In PCOS women, rs13405728 genotypes are associated with glucose and insulin metabolism. Moreover, rs2479106 genotypes were associated with increased WHR levels and an adverse serum lipid profile. Further, we observed a trend towards decreased PCOS susceptibility within carriers of the rs2479106 G-allele. Further studies in large Caucasian PCOS cohorts are warranted to confirm our findings.