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

*Vitamin D and aspects of female fertility (especially PCOS) – May 2017

Vitamin D and aspects of female fertility (especially PCOS) – May 2017

PCOS – Live birth strongly a function of vitamin D level – 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
1.4238 ng
1.5140 ng
4.4645 ng

Image
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.

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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"

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

AbstractObjective: 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


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.

PMID: 2648521

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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.

PMID: 22780885


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.
Copyright © 2012 Elsevier Ltd. All rights reserved.
PMID: 22500844


12,000 IU for 3 months 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. [Epub ahead of print]
Raja-Khan N1, Shah J2, Stetter CM3, Lott ME4, Kunselman AR3, Dodson WC5, Legro RS5.
Author information
Abstract
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.
CLINICAL TRIAL REGISTRATION NUMBER: NCT00907153.
Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
PMID: 24636395
Comment by VitaminDWiki - this study was so quick that the blood levels of vitamin D levels did not reach theraputic value (about 40 ng). Very unlikely to have any benefit from such a short trial without having an initial loading dose.


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.
PMID: 24770121


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

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.

PMID: 24717915


PCOS may be due to being overweight - Turkey (which 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.
PMID: 25339479


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

PCOS independent of Vitamin D - 2015 Meta-analysis

Image
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PCOS review not convinced of association with Vitamin D - April 2017

Vitamin D and Polycystic Ovary Syndrome: an Integrating Review
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Attached files

ID Name Comment Uploaded Size Downloads
7941 Polycystic Ovary.pdf PDF 2017 admin 25 Apr, 2017 14:52 94.51 Kb 20
6790 PCOS F2.jpg admin 15 Jun, 2016 00:22 38.34 Kb 903
6789 PCOS RCT.pdf PDF admin 14 Jun, 2016 22:21 562.19 Kb 147
6073 PCOS.pdf PDF 2015 admin 21 Oct, 2015 13:29 464.47 Kb 353
5807 PCOS Meta.jpg admin 17 Aug, 2015 02:32 51.49 Kb 2075
5806 nutrients-07-04555.pdf PDF 2015 admin 17 Aug, 2015 02:27 787.92 Kb 316
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