Fertility problem (PCOS) reduced by vitamin D, etc: many studies

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PCOS risk decreased 27% by Omega-3 (Mendelian study) – Sept 2024

Causal relationship between fertility nutrients supplementation and PCOS risk: a Mendelian randomization study
Front Endocrinol (Lausanne). 2024 Sep 24:15:1420004. doi: 10.3389/fendo.2024.1420004
Fang Shao 1, Shijia Xu 2, Haiyang Zhao 3 2, Furong Zhang 2, Xin Wang 2, Hui Wang 2 4

Did they p-hack until they found a variable with p < 0.05 ?

Background: Polycystic ovary syndrome (PCOS), a prevalent endocrine disorder in women of reproductive age, is mainly ameliorated through drugs or lifestyle changes, with limited treatment options. To date, numerous researchers have found that fertility nutrient supplements may benefit female reproductive health, but their direct impact on polycystic ovary syndrome risk remains unclear.

Methods: Our research employs Mendelian Randomization to assess how fertility nutrients affect PCOS risk. Initially, we reviewed 49 nutrients and focused on 10: omega-3 fatty acids, calcium, dehydroepiandrosterone, vitamin D, betaine, D-Inositol, berberine, curcumin, epigallocatechin gallate, and metformin. Using methodologies of Inverse Variance Weighting and Mendelian Randomization-Egger regression, we examined their potential causal relationships with PCOS risk.

Results: Our findings indicate omega-3 fatty acids reduced PCOS risk (OR=0.73, 95% CI: 0.57-0.94, P=0.016), whereas betaine increased it (OR=2.60, 95% CI: 1.09-6.17, P=0.031). No definitive causal relations were observed for calcium, dehydroepiandrosterone, vitamin D, D-Inositol, and metformin (P>0.05). Drug target Mendelian Randomization analysis suggested that increased expression of the berberine target gene BIRC5 in various tissues may raise PCOS risk (OR: 3.00-4.88; P: 0.014-0.018), while elevated expressions of curcumin target gene CBR1 in Stomach and epigallocatechin gallate target gene AHR in Adrenal Gland were associated with reduced PCOS risk (OR=0.48, P=0.048; OR=0.02, P=0.018, respectively).

Conclusions: Our research reveals that specific fertility nutrients supplementation, such as omega-3 fatty acids, berberine, and curcumin, may reduce the risk of PCOS by improving metabolic and reproductive abnormalities associated with it.
 Download the PDF from VitaminDWiki

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PCOS treatment needs about 3,000 IU of Vitamin D - meta-analysis Sept 2024

Optimizing vitamin D status in polycystic ovary syndrome: a systematic review and dose-response meta-analysis
Nutr Rev. 2024 Sep 1;82(9):1176-1186. doi: 10.1093/nutrit/nuad117 PDF behind paywall
Kelsey M Cochrane 1 2, Jeffrey N Bone 2 3, Brock A Williams 1 2, Crystal D Karakochuk 1 2

Context: Polycystic ovary syndrome (PCOS) is a common and complex endocrine disorder in women of reproductive age. Vitamin D supplementation is a promising complementary therapy for PCOS, yet there is no consensus on an optimal dose, leading to a lack of evidence-based supplementation guidelines.

Objective: The objective of this study was to conduct a vitamin D dose-response meta-analysis among women with PCOS.

Data sources: MEDLINE, CINAHL, and EMBASE databases from inception to November 2022 were searched for relevant articles.

Data extraction: Study screening and bias assessment were conducted by 2 independent reviewers. Eight relevant studies were identified; data for serum 25(OH)D (nmol/L) at baseline and at 12 weeks in each intervention group (mean ± SD) and vitamin D dose were extracted.

Data analysis: Estimates across studies were used to create a pooled curve, using restricted cubic splines with knots at the 10th, 50th, and 90th percentiles of the distribution of doses, to estimate the mean difference in effect for serum 25(OH)D at each dose compared with 0 IU/day. Sensitivity analyses were conducted fixing knots at 4000 IU/day and 7000 IU/day, which were a priori identified as potentially important thresholds, and to assess model fit and estimate heterogeneity. The pooled analysis demonstrated strong evidence of a dose-response relationship (P < .001), suggesting an increasing effect with increasing dose. An initial increase in serum 25(OH)D was evident until doses of approximately 3000 IU/day; this was followed by a plateau in effect between approximately 3000 IU/day and 5000 IU/day. The effect of supplementation with >5000 IU/day was unclear, given the minimal data at higher doses. The curve produced robust results for moderate doses (3000 IU/day to 4000 IU/day), which were not sensitive to model specification.

Conclusion: Women with PCOS are responsive to vitamin D supplementation, but the benefit of providing doses of >3000 IU/day appears minimal. Further data is required to determine dose-response at doses of >5000 IU/day, and whether higher intakes provide a clinically meaningful advantage in this population.

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Need more PCOS studies with >3,000 IU dosing - meta-analysis Sept 2023

Optimizing vitamin D status in polycystic ovary syndrome: a systematic review and dose-response meta-analysis
Nutr Rev . 2023 Sep 28;nuad117. doi: 10.1093/nutrit/nuad117 PDF is behind a paywall
Kelsey M Cochrane 1 2, Jeffrey N Bone 2 3, Brock A Williams 1 2, Crystal D Karakochuk 1 2

Context: Polycystic ovary syndrome (PCOS) is a common and complex endocrine disorder in women of reproductive age. Vitamin D supplementation is a promising complementary therapy for PCOS, yet there is no consensus on an optimal dose, leading to a lack of evidence-based supplementation guidelines.

Objective: The objective of this study was to conduct a vitamin D dose-response meta-analysis among women with PCOS.

Data sources: MEDLINE, CINAHL, and EMBASE databases from inception to November 2022 were searched for relevant articles.

Data extraction: Study screening and bias assessment were conducted by 2 independent reviewers. Eight relevant studies were identified; data for serum 25(OH)D (nmol/L) at baseline and at 12 weeks in each intervention group (mean ± SD) and vitamin D dose were extracted.

Data analysis: Estimates across studies were used to create a pooled curve, using restricted cubic splines with knots at the 10th, 50th, and 90th percentiles of the distribution of doses, to estimate the mean difference in effect for serum 25(OH)D at each dose compared with 0 IU/day. Sensitivity analyses were conducted fixing knots at 4000 IU/day and 7000 IU/day, which were a priori identified as potentially important thresholds, and to assess model fit and estimate heterogeneity. The pooled analysis demonstrated strong evidence of a dose-response relationship (P < .001), suggesting an increasing effect with increasing dose. An initial increase in serum 25(OH)D was evident until doses of approximately 3000 IU/day; this was followed by a plateau in effect between approximately 3000 IU/day and 5000 IU/day. The effect of supplementation with >5000 IU/day was unclear, given the minimal data at higher doses. The curve produced robust results for moderate doses (3000 IU/day to 4000 IU/day), which were not sensitive to model specification.

Conclusion: Women with PCOS are responsive to vitamin D supplementation, but the benefit of providing doses of >3000 IU/day appears minimal. Further data is required to determine dose-response at doses of >5000 IU/day, and whether higher intakes provide a clinically meaningful advantage in this population.

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PCOS and vitamin D: a clinical appraisal - Sept 2023

Arch Gynecol Obstet. 2023 Sep 25. doi: 10.1007/s00404-023-07227-x
Radmila Sparic 1 2, Mladen Andjic 1, Daniele Vergara 3, Andrea Morciano 4, Ottavia D'Oria 5 6, Giorgio Maria Baldini 7, Antonio Malvasi 8, Andrea Tinelli 9

Purpose: Polycystic ovary syndrome (PCOS) is the most common endocrine-reproductive disease linked not just to infertility but also to serious comorbidities. There is a reported association between low vitamin D levels and multiple health conditions including PCOS. This narrative review aims to analyze the role of vitamin D in PCOS development, use of the vitamin D in the treatment of PCOS, and the molecular basis of these observations.

Methods: A Medline and PubMed research was performed, during the years 1990-2023, using a combination of keywords on such topic. According to the author's evaluation and target, papers were identified and included for a narrative review.

Results: There are associations between lower levels of vitamin D and PCOS, as well as with insulin resistance, metabolic syndrome, hyperandrogenemia, metabolic and endocrine disorders as well as the onset of oxidative stress and pro-inflammatory milieu, in PCOS women.

Conclusion: Vitamin D has a role in pathologic changes linked to PCOS. Molecular and clinical investigations which give new information about the role of vitamin D in the development of PCOS and related endocrine and metabolic disturbance are further needed.
 Download the PDF from VitaminDWiki

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PCOS is more than just a fertility problem - PCOS reduces longevity by 1 year - 2023

PCOS associated with shorter lifespan MDEdge June 2023*"In the study, involving nearly 10,000 women with PCOS and matched controls from Finland, women with PCOS died on average a year earlier than their age-matched counterparts, primarily from diseases of the circulatory system, cancer, and diabetes."

• “PCOS is largely a metabolic condition rooted in insulin resistance, and therefore, the potential clinical outcomes, including mortality, are important to recognize.”
• 10% of all women have PCOS
• PCOS increased risk of deaths: Cancer 1.39, Circultory 1.68, hypertensive heart disease, pulmonary embolism, etc. 2.06, diabetes 2.85

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11+ VitaminDWiki pages with PCOS in title

This list is automatically updated

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VitaminDWiki – Vitamin D greatly improves Fertility

141 items

• Vitamin D is needed for human fertility – goal is 50 ng – Sept 2018
• In-vitro Fertilization costs at least 10,000 dollars, Vitamin D costs 5 dollars
• Infertile patients 1.7X more-likely to become pregnant if take Vitamin D – meta-analysis Feb 2023
• Live birth 1.7 X more likely after IVF if good level of vitamin D – meta-analysis Aug 2020
• If diagnosed infertile, more likely to have live birth if Vitamin D fortification – Feb 2020
• Preconception vitamin D is great - every extra 10 ng associated with 10 percent more likely to have live birth – Aug 2018
• Women with more than minimum vitamin D were 3.4 X more likely to achieve pregnancy and 1.6 X more likely to have live births – June 2017
• Assisted Reproduction – 5 studies concluded vitamin D repletion helps – Review March 2015
• Pregnancy success increased 30 percent if sunny (or vitamin D) one month earlier – June 2015
• IVF 4X more successful for white women with lots of vitamin D – many studies

Increased male Vitamin D increases fertility

• Birth rates doubled with Vitamin D - 300,000 for infertile men – RCT Nov 2017
• Higher vitamin D results in 22% fewer abnormal sperm (Mendelian analysis) – May 2024
• Conception was 3.7X more likely if the male had a good level of Vitamin D – July 2022
• Far better sperm in fertility clinic if more than 30 ng of Vitamin D - June 2022
• Fertility (sperm) associated with vitamin D – meta-analysis Sept 2019
• Infertility - 71 percent of the time of BOTH partners had less than 20 ng of Vitamin D – Aug 2017
• Male fertility 4 X higher if high Vitamin D – Nov 2015
• Vitamin D somewhat assists reproduction – both the mother and the father – May 2014

Decreased Fertility if decreased Vitamin D Receptor

• Unexplained infertility 4X more likely if poor vitamin D receptor – Dec 2020
• Male Infertility is associated with poor Vitamin D Receptor – July 2021

• Overview Conception and vitamin D
  • Vitamin D increases fertility of BOTH the man and the woman.
  • Each 1 ng increase in blood level of vitamin D increases fertility by 1%.
  • Vitamin D has been used by zoos and vets for a long time to increase birth rate
• ALL of the top 10 health problems of women are associated with low vitamin D
• Vitamin D and fertility: a systematic review – May 2012 has the following graphic

VitaminDWiki – Vitamin D and Omega-3 category contains

407 Omega-3 items in category Omega-3 helps with: Autism (7 studies), Depression (28 studies), Cardiovascular (34 studies), Cognition (52 studies), Pregnancy (44 studies), Infant (34 studies), Obesity (14 studies), Mortality (7 studies), Breast Cancer (5 studies), Smoking, Sleep, Stroke, Longevity, Trauma (12 studies), Inflammation (18 studies), Multiple Sclerosis (9 studies), VIRUS (12 studies), etc
CIlck here for details

See also: Omega-3 and women

• Fertility of defrosted sperm better if had increased dietary Omega-3 – many studies
• Omega-3 – fewer than 5 percent of adult women get the RDA – April 2018
• Preterm birth rate of pregnant smokers cut in half if take Omega-3 – RCT May 2017
• Women are 30 percent less likely to die if have good level of Omega-3 – Jan 2017

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PCOS appears to be helped by Vitamn D, probiotics, Omega-3, etc - meta-analysis Sept 2022

Effects of nutrition on metabolic and endocrine outcomes in women with polycystic ovary syndrome: an umbrella review of meta-analyses of randomized controlled trials
Nutr Rev . 2022 Sep 13;nuac075. doi: 10.1093/nutrit/nuac075 $39 paywall
Nazanin Moslehi 1 , Sheida Zeraattalab-Motlagh 2 , Fatemeh Rahimi Sakak 1 , Sakineh Shab-Bidar 2 , Fahimeh Ramezani Tehrani 3 , Parvin Mirmiran 1 4

Context: Numerous meta-analyses have been conducted on the effects of nutritional interventions on various health outcomes in women with polycystic ovary syndrome (PCOS). However, the strength of the evidence and its clinical significance are unclear.

Objective: This umbrella review aimed to summarize the effects of nutritional interventions on women with PCOS and assess the strength of the evidence.

Data sources: PubMed, Scopus, and Web of Science were searched from inception until March 17, 2021.

Data extraction: Meta-analyses of randomized clinical trials (RCTs) that examined the impact of dietary modifications or supplementations on women with PCOS were selected. Data extraction, quality assessments of the meta-analyses, and evaluation of the strength of the evidence were conducted independently by 2 investigators and confirmed by a third.

Data analysis: Twenty-eight RCT meta-analyses were included, reporting 40 different outcomes. Lower carbohydrate, Dietary Approaches to Stop Hypertension, or lower glycemic index/load diets in women with PCOS significantly improved some anthropometric and metabolic characteristics (with very low to low certainty). Probiotics/synbiotics reduced fasting plasma glucose, fasting insulin (FI), and homeostasis model assessment-estimated insulin resistance (HOMA-IR) (with moderate to high certainty). Curcumin supplementation decreased fasting plasma glucose, FI, and HOMA-IR (with moderate certainty). Fish oil supplementation decreased FI and HOMA-IR, and omega-3 reduced triglycerides (with moderate certainty). There were also improvements in FI after taking vitamin D or inositol supplements (with moderate certainty). Supplementation with fish oil increased adiponectin (with high certainty), and probiotics/synbiotics reduced total testosterone (with moderate certainty). In subfertile women with PCOS, inositol increased the ovulation rates (with moderate certainty).

Conclusion: There was no high-certainty evidence that diets alone in women with PCOS improved health or reproductive outcomes.
Supplementation with vitamin D, probiotics/synbiotics, omega-3, inositol, and curcumin showed favorable effects on some metabolic outcomes. Probiotics/synbiotics possibly reduces total testosterone, and inositol stimulates ovulation in women with PCOS.

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PCOS Physiopathology and Vitamin D Deficiency - Aug 2022

Biological Insights and Perspectives for Treatment
J. Clin. Med. 2022, 11(15), 4509; https://doi.org/10.3390/jcm11154509
by Giuseppe Morgante †ORCID,Ilenia Darino †,Amelia Spanò,Stefano Luisi,Alice LuddiORCID,Paola Piomboni,Laura Governini *ORCID andVincenzo De Leo
Department of Molecular and Developmental Medicine, University of Siena, 53100 Siena, Italy

Recent literature has stressed the importance of vitamin D (VD) in polycystic ovary syndrome (PCOS). Women with PCOS are deficient in VD, particularly those with a higher weight. Hypovitaminosis is a risk factor for glucose intolerance, and reduced levels of VD is associated with insulin resistance and increased diabetes risk. Since women with PCOS and hirsutism seem to have lower levels of VD than women with PCOS without hirsutism, a correlation between VD deficiency and hyperandrogenism may be suggested. Interestingly, VD is crucial for many human physiological functions, including to counteract inflammation and oxidative stress. Some studies evaluated effects of VD supplementation on glucose homeostasis variables, hormonal status, lipid concentrations, and biomarkers of inflammation and oxidative stress among VD-deficient women. Moreover, VD has been shown to play a role in egg quality and fertility. This review aims to show the relationship between VD and the endocrine and metabolic profile of PCOS patients, as well as its implications for their fertility. The supplement of VD to the common therapy can lead to an improvement of the insulin resistance and lipid metabolism, a reduction of circulating androgens, as well as a better response to the induction of ovulation in PCOS women.
 Download the PDF from VitaminDWiki

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PCOS - menstrual frequency improved by 50,000 IU Vitamin D/week & low calorie diet - RCT May 2018

The effect of vitamin D supplementation in combination with low-calorie diet on anthropometric indices and androgen hormones in women with polycystic ovary syndrome: a double-blind, randomized, placebo-controlled trial
.J Endocrinol Invest. 2018 May;41(5):597-607. doi: 10.1007/s40618-017-0785-9. Epub 2017 Nov 6.
Jafari-Sfidvajani S1,2, Ahangari R3, Hozoori M4, Mozaffari-Khosravi H2,5, Fallahzadeh H6, Nadjarzadeh A7,8.

PURPOSE:
Polycystic ovary syndrome (PCOS) is known as the most common endocrine disorder in reproductive age women. The aim of this study low calorie diet was to evaluate the effects of vitamin D supplementation in combination with low-calorie diet on anthropometric indices, reproductive hormones and menstrual regularity in overweight and obese PCOS women.

METHODS:
In this randomized controlled clinical trial, 60 PCOS women with vitamin D insufficiency were randomly assigned to 12 weeks of either

• (1) weight-loss intervention + 50,000 IU/week oral vitamin D3 or
• (2) weight-loss intervention + placebo.

At the beginning and end of the study, the anthropometric indices, body composition, 25-hydroxyvitamin D, total testosterone, dehydroepiandrosterone sulfate (DHEAS), sex hormone-binding globulin (SHBG) and free androgen index (FAI) were measured and regularity of menses was compared among the two groups.

RESULT:
After 12-week intervention, median of serum 25-hydroxyvitamin D3 significantly increased from 18.5 (10.75-20) ng/ml to 42.69 (34-53.25) ng/ml in vitamin D group compared to placebo group (p < 001). Moreover, there was a significant improvement in frequency regular menstrual cycle (p = 0.01). Mean of weight, body mass index, fat mass, waist and hip circumference and waist-to-hip ratio significantly decreased in both groups, but was not different between two groups. Mean of total testosterone insignificantly decreased from 0.7 to 0.5 ng/ml in vitamin D group (p = 0.18). In addition, we did not observe significant differences regarding DHEAS, FAI and SHBG between two groups.

CONCLUSIONS:In women with PCOS, androgen profile did not change with vitamin D supplementation when combined with low-calorie diet, but menstrual frequency significantly improved.
CLINICAL TRIAL REGISTRATION NUMBER: IRCT2016062710826N19.

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PCOS problems reduced by Vitamin D plus Omega-3 – RCT June 2018

The influences of vitamin D and omega-3 co-supplementation on clinical, metabolic and genetic parameters in women with polycystic ovary syndrome.
J Affect Disord. 2018 May 26;238:32-38. doi: 10.1016/j.jad.2018.05.027. [Epub ahead of print]

PDF is available free at Sci-Hub

Jamilian M1, Samimi M2, Mirhosseini N3, Afshar Ebrahimi F2, Aghadavod E4, Talaee R5, Jafarnejad S4, Hashemi Dizaji S6, Asemi Z7.
1 Endocrinology and Metabolism Research Center, Department of Gynecology and Obstetrics, School of Medicine, Arak University of Medical Sciences, Arak, Iran.
2 Department of Gynecology and Obstetrics, School of Medicine, Kashan University of Medical Sciences, Kashan, IR, Iran.
3 Pure North S'Energy Foundation, Calgary, AB, Canada.
4 Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, IR, Iran.
5 Department of Dermatology, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran.
6 Department of Gynecology and Obstetrics, School of Medicine, Iran University of Medical Sciences, Tehran, Iran. Electronic address: dr.shahrzad.hashemi.1 at gmail.com.
7 Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, IR, Iran. Electronic address: asemi_r at yahoo.com.

OBJECTIVE: The aim of this study was to evaluate the effect of the co-administration of vitamin D and omega-3 fatty acid on clinical, metabolic and genetic parameters in women with polycystic ovary syndrome (PCOS).

METHODS: This randomized, double-blinded, placebo-controlled clinical trial was conducted on 60 subjects, aged 18-40 years old with PCOS.
Subjects were randomly allocated to take either

• 50,000 IU vitamin D every 2 weeks
• plus 2000 mg/day omega-3 fatty acid from fish oil (n = 30)
  (or placebo (n = 30) for 12 weeks.

Gene expression analysis of inflammatory cytokines was conducted on peripheral blood mononuclear cells (PBMCs) of PCOS women using RT-PCR method.

RESULTS:
Vitamin D and omega -3 fatty acid co-supplementation

• significantly decreased serum total testosterone levels (-0.2 ± 0.5 vs. + 0.1 ± 0.4 ng/mL, P = 0.02) compared with the placebo.

In addition, vitamin D and omega-3 fatty acid co-supplementation resulted in a significant improvement in

• beck depression inventory (-1.4 ± 1.6 vs. -0.5 ± 0.6, P = 0.01),
• general health questionnaire scores (-4.5 ± 4.3 vs. -1.9 ± 2.3, P = 0.005) and
• depression anxiety and stress scale scores (-5.0 ± 5.1 vs. -2.3 ± 3.5, P = 0.01)

compared with the placebo.
Additionally, vitamin D and omega-3 fatty acid co-administration significantly

• decreased serum high-sensitivity C-reactive protein (hs-CRP) (-1.2 ± 1.9 vs. + 0.1 ± 0.7 mg/L, P = 0.001)
• and malondialdehyde (MDA) levels (-0.4 ± 0.4 vs. + 0.2 ± 0.6 µmol/L, P < 0.001), and
• significantly increased plasma total antioxidant capacity (TAC) levels (+ 114.6 ± 122.2 vs. -2.4 ± 168.2 mmol/L, P = 0.003)

compared with the placebo.
Results of RT-PCR demonstrated that vitamin D and omega-3 fatty acid co-supplementation significantly downregulated gene expression of interleukin-1 (IL-1) (P = 0.03), and upregulated vascular endothelial growth factor (VEGF) (P = 0.004) in PBMCs of subjects with PCOS, when compared with placebo.

CONCLUSIONS: Overall, the co-administration of vitamin D and omega-3 fatty acid for 12 weeks had beneficial effects on mental health parameters, serum total testosterone, hs-CRP, plasma TAC and MDA levels, and gene expression of IL-1 and VEGF among women with PCOS.

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PCOS – Live birth strongly a function of vitamin D level – RCT May 2016

Vitamin D Status Relates to Reproductive Outcome in Women with Polycystic Ovary Syndrome: Secondary Analysis of a Multicenter Randomized Controlled Trial
JCEM

Live Birth odds ratio	Vitamin D level
0.58	< 30 ng
1.42	38 ng
1.51	40 ng
4.46	45 ng

Setting: Secondary analysis of randomized controlled trial (RCT) data.

Participants: Pregnancy in PCOS-I (PPCOS I) RCT (n540); participants met the NIH diagnostic criteria for PCOS.

Interventions: Serum 25OHD (ng/ml; for conversion to SI units [nmol/L], multiply by 2.5) levels were measured in stored sera.

Main outcome measures: Primary (Live birth- LB); secondary (ovulation-OV and pregnancy loss-PL) following ovulation induction (OI)

Results: Likelihood for LB was reduced by 44% for women if 25OHD level was 30 ng/ml (75 nmol/L, OR 0.58 [0.35– 0.92]). Progressive improvement in the odds for LB was noted at thresholds of 38ng/ml, (95 nmol/L, OR 1.42 [1.08- 1.8]), 40ng/ml (100 nmol/L, OR1.51 [1.05–2.17] and 45ng/ml (112.5 nmol/L, OR 4.46 [1.27–15.72]). On adjusted analyses, VitD status was an independent predictor of LB and OV following OI.

Conclusions: In women with PCOS, serum 25OHD was an independent predictor of measures of reproductive success following OI. Our data identify reproductive thresholds for serum 25OHD that are higher than recommended for the non-pregnant population.

 Download the PDF from VitaminDWiki
Clips from PDF

• "Nearly 10% of reproductive age women (6.1 million) in the U.S. have difficulty achieving pregnancy with ovulatory dysfunction being a major cause of female infertility"

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PCOS decreased by 2.3 X with Vitamin D - meta-analysis Feb 2017

Effect of vitamin D supplementation on polycystic ovary syndrome: A systematic review and meta-analysis of randomized controlled trials
Complementary Therapies in Clinical Priactice, DOI: http://dx.doi.org/10.1016/j.ctcp.2016.11.008 |
Fang Fang, Ke Ni, Yiting Cai, Jin Shang, Xiaoke Zhang, Chengliang Xiong

Objective: To evaluate the effect of vitamin D supplementation on patients with PCOS.

Methods
We performed a literature search in database and identified all of the RCTs published before December 2015 that compared the effect of vitamin D supplementation with placebo or metformin in PCOS patients.

Main results
Nine out of 463 identified studies were included, involving 502 women presenting with PCOS. Vitamin D supplementation had significant effect on the improvement of follicular development with a higher number of dominant follicles (OR, 2.34; 95% CI, 1.39 to 3.92). Differences in regular menstrual cycles were also observed when metformin plus vitamin D was compared with metformin alone (OR, 1.85; 95% CI, 1.01 to 3.39).

Conclusions
Evidence from available RCTs suggests vitamin D supplementation may be beneficial for follicular development and menstrual cycle regulation in patients with PCOS. Additional high-quality RCTs are required to confirm the effectiveness of vitamin D on PCOS.
Publisher wants $36 for the PDF

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PCOS problems greatly reduced by Vitamin D (50,000 IU weekly) – Oct 2015

Vitamin D Supplementation Decreases TGF-β1 Bioavailability in PCOS: A Randomized Placebo-Controlled Trial.
J Clin Endocrinol Metab. 2015 Oct 20:jc20152580. [Epub ahead of print]
Irani M, Seifer DB, Grazi RV, Julka N, Bhatt D, Kalgi B, Irani S, Tal O, Lambert-Messerlian G, Tal R.

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 prospective, randomized, 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, dehydroepiandrosterone 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;
 Download the PDF from VitaminDWiki

Therapeutic implications of vitamin D and calcium in overweight women with polycystic ovary syndrome. (8500 IU, 2012)

Gynecol Endocrinol. 2012 Jul 11.
Pal L, Berry A, Coraluzzi L, Kustan E, Danton C, Shaw J, Taylor H.
Obstetrics, Gynecology & Reproductive Sciences, Yale University School of Medicine , New Haven, CT , USA.

Objective: To assess effects of vitamin D and Calcium (Ca) on hormonal and metabolic milieu of polycystic ovary syndrome (PCOS).

Design: Single arm open label trial.

Methods: Twelve overweight and vitamin D deficient women with PCOS underwent a 2?hour oral glucose tolerance testing at baseline and following 3-month supplementation with vitamin D (daily dose of 3533 IU, increased to 8533 IU after the first five participants) and 530?mg elemental Ca daily.

Main outcome measures: Blood pressure (BP), plasma glucose, insulin, total testosterone (T) androstenedione (A), sex hormone binding globulin, lifestyle parameters were assessed at baseline and following 3-month intervention. Insulin resistance (IR) and area under the curve for glucose and insulin were computed; paired analyses were conducted.

Results:

• Improved serum 25OHD (p < 0.001) and
• reductions in total T (p = 0.036) and
• A (p = 0.090) levels

were noted following 3-month supplementation, compared to baseline.
Significant lowering in BP parameters was seen in participants with baseline BP ? 120/80 mmHg (n = 8) and in those with baseline serum 25OHD ?20?ng/ml (n = 9). Parameters of glucose homeostasis and IR remained unchanged (p > 0.05).

Conclusions: Androgen and BP profiles improved followed three month intervention, suggesting therapeutic implications of vitamin D and Ca in overweight and vitamin D deficient women with PCOS.

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Vitamin D seems to have helped PCOS somewhat (2012)

Therapeutic effects of calcium & vitamin D supplementation in women with PCOS.
Complement Ther Clin Pract. 2012 May;18(2):85-8. Epub 2012 Feb 20.
Firouzabadi Rd, Aflatoonian A, Modarresi S, Sekhavat L, MohammadTaheri S.
Research and Clinical Center for Infertility, Shahid Sedughi University of Medical Sciences and Health Services, Yazd, Iran. dr_firouzabadi at ssu.ac.ir

OBJECTIVE: To evaluate the efficacy of calcium & vitamin D supplementation in infertile women suffering from polycystic ovary syndrome (PCOS), and to assess levels of 25-hydroxy vitamin D in these patients.

METHODS: In a case control study, 100 infertile PCOS women based on a randomly divided into two groups.

• Group I (n = 50) were treated with metformin 1500 mg/day, and
• group II (n = 50) treated with metformin 1500 mg/day plus Calcium 1000 mg/day and Vitamin D 100000 IU/month for 6 months.

Patients were followed by transvaginal sonography at first, 3 and 6 months later for evaluating dominant follicle. BMI, menstrual regularity, follicle diameter, pregnancy, serum 25-OH-vitamin D level were matured and compared in two groups.

RESULTS: BMI decreased almost significantly (25.49 ± 1.88 vs 26.28 ± 2.15, p: 0.054) in group II.
A better improvement was gained in regulating

• menstrual abnormalities (70% vs 58%, p: 0.211),
• follicle maturation (28% vs 22%, p: 0.698), and
• infertility (18% vs 12%, p: 0.401) in group II compared with group I,

but these results were not statistically significant.
Eighty three percent of all the PCOS patients showed vitamin D deficiency while 35% were severely deficient.
The serum 25-OH-vitamin D mean levels were 13.38 ± 6.48 ng/ml. Vitamin D deficiency was recompensed in 74% of the PCOS patients who had taken calcium & vitamin D supplementation.
There was no correlation between BMI and 25-OH-VD before and after the treatment (p ? 0.01).

CONCLUSION: This study showed the positive effects of calcium & vitamin D supplementation on weight loss, follicle maturation, menstrual regularity, and improvement of hyperandrogenism, in infertile women with PCOS.

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12,000 IU daily for a short time did not help much - RCT March 2014 (achieved only 25 ng)

High-dose vitamin D supplementation and measures of insulin sensitivity in polycystic ovary syndrome: a randomized, controlled pilot trial.
Fertil Steril. 2014 Mar 14. pii: S0015-0282(14)00174-5. doi: 10.1016/j.fertnstert.2014.02.021
Raja-Khan N1, Shah J2, Stetter CM3, Lott ME4, Kunselman AR3, Dodson WC5, Legro RS5.

OBJECTIVE: To determine the effects of high-dose vitamin D on insulin sensitivity in polycystic ovary syndrome (PCOS).
DESIGN: Randomized, placebo-controlled trial.
SETTING: Academic medical center.
PATIENT(S): Twenty-eight women with PCOS.
INTERVENTION(S): 0Vitamin 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.

Comment by VitaminDWiki - this study duration was so short that the vitamin D levels did not reach a theraputic value (about 40 ng). Very unlikely to have any benefit from such a short trial without having an initial loading dose.

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Probable connection: antimüllerian hormone levels - April 2014 50,000 IU weekly helped

Vitamin d normalizes abnormally elevated serum antimüllerian hormone levels usually noted in women with polycystic ovary syndrome.
Obstet Gynecol. 2014 May;123 Suppl 1:189S. doi: 10.1097/01.AOG.0000447216.52829.8e.
Irani M1, Seifer D, Minkoff H, Merhi Z.

INTRODUCTION:
Antimüllerian hormone is abnormally elevated in the serum of women with polycystic ovary syndrome (PCOS). Elevated antimüllerian hormone in PCOS plays a key role in ovulatory dysfunction. The epidemic of vitamin D deficiency affects reproductive potential. Vitamin D3 therapy has been suggested to improve the metabolic disturbances observed in women with PCOS. We hypothesized that vitamin D3 supplementation improves follicular health in vitamin D-deficient women with PCOS, as reflected by normalization of the abnormally elevated antimüllerian hormone serum levels.
METHODS:
Fifty-seven women without PCOS and 20 with PCOS diagnosed with vitamin D deficiency (less than 20 ng/mL) were either treated with 50,000 IU of vitamin D3 once weekly for 8 weeks (n=16 PCOS, 45 non-PCOS) or not treated (n=4 PCOS, 12 non-PCOS). Serum 25-hydroxyvitamin D (ng/mL) and antimüllerian hormone concentrations (ng/mL) were measured before and after 8 weeks of supplementation in the treated group and 8 weeks apart in the control group. Paired t test and Wilcoxon signed rank test were used as appropriate.
RESULTS:
Compared with women in a control group, antimüllerian hormone concentration of women with PCOS significantly dropped after vitamin D3 supplementation (from 5.3±0.6 to 3.9±0.5, P=.003). Vitamin D3 supplementation did not alter antimüllerian hormone levels in non-PCOS women (P=.6). All participants showed a negative correlation between age and antimüllerian hormone (P<.05). As the body mass index of participants increased, there was a smaller elevation in serum 25-hydroxyvitamin D after supplementation (P<.05).
CONCLUSION:
In vitamin D-deficient women with PCOS, appropriate vitamin D3 supplementation seems to improve follicular development and ovarian health as reflected by normalization of serum antimüllerian hormone. Additionally, obese women require higher doses of vitamin D3 supplementation. Funding provided by the Maimonides Research and Development Foundation.

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> 30 ng recommended to reduce PCOS (June 2014)

Vitamin D and female fertility.
Curr Opin Obstet Gynecol. 2014 Jun;26(3):145-50. doi: 10.1097/GCO.0000000000000065.
Lerchbaum E1, Rabe T.

PURPOSE OF REVIEW: Apart from the well known effects of vitamin D on maintaining calcium homeostasis and promoting bone mineralization, there is some evidence suggesting that vitamin D also modulates human reproductive processes. We will review the most interesting and relevant studies on vitamin D and female fertility published over the past year.

RECENT FINDINGS: In the past year, several observational studies reported a better in-vitro fertilization outcome in women with sufficient vitamin D levels (≥30 ng/ml), which was mainly attributed to vitamin D effects on the endometrium. One randomized controlled trial found an increased endometrial thickness in women with polycystic ovary syndrome (PCOS) receiving vitamin D during intrauterine insemination cycles. Further, vitamin D supplementation had a beneficial effect on serum lipids in PCOS women. Vitamin D treatment improved endometriosis in a rat model and increased vitamin D intake was related to a decreased risk of incident endometriosis. Vitamin D was also favorably associated with primary dysmenorrhea, uterine leiomyoma, and ovarian reserve in late reproductive aged women.

SUMMARY: In women undergoing in-vitro fertilization, a sufficient vitamin D level (≥30 ng/ml) should be obtained.
Vitamin D supplementation might improve metabolic parameters in women with PCOS.
A high vitamin D intake might be protective against endometriosis.

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PCOS may be due to being overweight - Turkey (which also has low Vit D) Oct 2014

Intrinsic factors rather than vitamin D deficiency are related to insulin resistance in lean women with polycystic ovary syndrome.
Eur Rev Med Pharmacol Sci. 2014 Oct;18(19):2851-6.
Sahin S1, Eroglu M, Selcuk S, Turkgeldi L, Kozali S, Davutoglu S, Muhcu M.
1Zeynep Kamil Woman's and Children's Disease Training and Research Hospital, Istanbul, Turkey. drsadiksahin at gmail.com.

OBJECTIVE:
To investigate the correlation between insulin resistance (IR) and serum 25-OH-Vit D concentrations and hormonal parameters in lean women with polycystic ovary syndrome (PCOS).
PATIENTS AND METHODS:
50 lean women with PCOS and 40 body mass index (BMI) matched controls were compared in terms of fasting insulin and glucose, homeostatic model assessment insulin resistance (HOMA-IR), 25-OH-Vit D, high sensitivity C-reactive protein (hs-CRP), luteinizing hormone (LH), follicle-stimulating hormone (FSH), total testosterone, dehydroepiandrosterone sulfate (DHEA-S), total cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), triglycerides and Ferriman-Gallway (FG) scores. Correlation analyses were performed between HOMA-IR and metabolic and endocrine parameters.
RESULTS:
30% of patients with PCOS demonstrated IR. Levels of 25-OH-Vit D, hsCRP, cholesterol, HDL, LDL, triglyceride and fasting glucose did not differ between the study and control groups. Fasting insulin, HOMA-IR, LH, total testosterone, and DHEA-S levels were higher in PCOS group. HOMA-IR was found to correlate with hs-CRP and total testosterone but not with 25-OH-Vit D levels in lean patients with PCOS.
CONCLUSIONS:
An association between 25-OH-Vit D levels and IR is not evident in lean women with PCOS. hs-CRP levels do not indicate to an increased risk of cardiovascular disease in this population of patients. Because a strong association between hyperinsulinemia and hyperandrogenism exists in lean women with PCOS, it is advisable for this population of patients to be screened for metabolic disturbances, especially in whom chronic anovulation and hyperandrogenism are observed together.

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Wikipedia highlights on PCOS

• Polycystic ovary syndrome (PCOS) is one of the most common female endocrine disorders.
• PCOS produces symptoms in approximately 5% to 10% of women of reproductive age
• It is thought to be one of the leading causes of female subfertility
• Common symptoms of PCOS include:
  Menstrual disorders
  High levels of masculinizing hormones
  Metabolic syndrome

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PCOS decreased by Magnesium, Zinc, Calcium, and 200 IU of VitaminD - March 2018

• Magnesium-Zinc-Calcium-Vitamin D Co-supplementation Improves Hormonal Profiles, Biomarkers of Inflammation and Oxidative Stress in Women with Polycystic Ovary Syndrome: a Randomized, Double-Blind, Placebo-Controlled Trial. doi: 10.1007/s12011-017-1085-0
  100 mg magnesium, 4 mg zinc, 400 mg calcium plus 200 IU vitamin D for 12 weeks

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PCOS treatment by Vitamin D is aided by Metformin - meta-analysis Feb 2024

doi: 10.29063/ajrh2024/v28i2.4 PDF is behind a paywall
Our meta-analysis of nine trials demonstrates significant reductions in insulin resistance, BMI, and testosterone levels, along with increased serum vitamin D levels and improved menstrual cycle regulation after Metformin and vitamin D treatment. These findings suggest the potential of this combined therapy in managing the multifaceted aspects of PCOS.
See vitaminDwiki: ‘Cracking the Aging Code' with vitamin D, Metformin, etc. Book June 2016

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See also web

• Vitamin D and polycystic ovary syndrome- Nov 2022 - https://doi.org/10.1016/j.tjog.2022.06.010  PDF
• PCOS website
• VITAMIN D FOR PCOS FERTILITY (AND EVERYTHING ELSE) PCOS Diva, April 2019

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