Vitamin D Significantly Corrects PCOS Dysfunction

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Vitamin D significantly corrects PCOS dysfunction

Androgens and hirsutism score of overweight women with polycystic ovary syndrome improved after vitamin D treatment: A randomized placebo controlled clinical trial

doi.org/10.1016/j.clnu.2020.09.024

Background

Previous observational studies identified an association between vitamin D levels and markers of hyperandrogenism.

Hirsutism, total testosterone (TT), dehydroepiandrosterone sulphate (DHEAS) and free androgen index are all negatively associated with vitamin D levels while sex hormone binding globulin (SHBG) is positively associated.

Low levels of vitamin D has also been linked to obesity, insulin resistance and impaired follicle development via altered Anti-Müllerian hormone (AMH) signalling, follicular stimulating hormone (FSH) response, and the regulation of progesterone in human granulosa cells within the ovaries.

Studies testing the effect of vitamin D3 supplementation on hyperandrogenism have had mixed results, most likely due to small patient numbers, differing doses and duration.

However no studies to date have evaluated the effect of high dose (50,000 IU/week) vitamin D treatment, in women with PCOS, for a period of 12 weeks or more.

Aim

To evaluate the impact of 50,000 IU/week supplementation of vitamin D3 on androgen levels and hirsutism scores in obese women with PCOS.

Methodology

Overweight women, aged 18 to 49, diagnosed with PCOS were recruited initially for assessment. Only women with a BMI between 25 and 29.9 kg/m2, low vitamin D levels (<20 ng/ml) and dietary intake (<600 IU/day), normal levels of aspartate and alanine aminotransferase, urea, and creatinine, along with a normal blood count, were allowed to participate in the trial.

PCOS was confirmed using the Rotterdam criteria, after excluding other possible causes such as androgen secreting tumors, Cushing syndrome, congenital adrenal hyperplasia, hyperthyroidism and hyperprolactinemia.

Any woman who was lactating, pregnant, diagnosed with diabetes, hyperthyroidism, hypothyroidism, liver or cardiovascular disease, renal dysfunction, food allergies, drug or alcohol abuse, smoked hookah or cigarettes (>9/day), or was taking medication that altered their metabolic parameters, was automatically excluded from the study to minimise potential bias.

Following initial assessment, a total of 60 women, who satisfied the inclusion exclusion criteria, were randomly assigned to either the placebo (n=30) or treatment group (n=30). Women in the treatment group were given 12 vitamin D3 tablets (50,000 IU/tablet) to take once a week, for a total of 12 weeks, while women in the control group received a placebo identical in shape, colour, size and packaging to take similarly.

Serum vitamin D, 25(OH)D levels, was measured at several intervals, in both groups of women, specifically 7 days prior to the study, followed by day 0, 30, 60, 90, and then one final time, 14 days after the last dose.

Blood samples were collected following an overnight fast, with hirsutism assessed via the Ferriman-Gallwey scoring system and HOMA-IR (Homeostasis model of assessment of insulin resistance) calculated as per standard equations.

Ovarian volume, number of follicles and size was recorded using ultrasound. Regular cycles was defined as menstruation occurring between 21 to 35 days, with everything else considered irregular.

Results

Of the 60 women who began the intervention trial, 1 dropped out from each group, resulting in 58 women who completed the trial.

Mean age was 23.7 years, with a BMI of 27.1kg/m2 and mean hirsutism score of 16.7. Prevalence of vitamin D deficiency was 91.4%.

Initial analysis of general characteristics showed no statistically significant differences between the 2 groups of women (P>0.07).

Following the trial, analysis of serum 25(OH)D levels confirmed a significant increase in vitamin D levels, during all measurement intervals other than baseline, for the treatment group compared to placebo.

This had a positive effect on various parameters, with significant decreases to total testosterone (1.6 vs. 2.1 nmol/L), Free Androgen Index (4.5 vs. 6.3), hirsutism (11.5 vs. 16.5), fasting blood glucose (4.5 vs. 4.9 mmol/L) and parathyroid hormone (39.1 vs. 65.3 Pg/ml), whilst SHBG (85.9 vs. 51.7 nmol/L) and progesterone (5.8 vs. 5.2 nmol/L) levels improved significantly. 

Even more significant was the effect on menstrual cycles, with regular cycles returning to 24/26 women in the treatment group who commenced the trial with irregular cycles. This result was supported by changes to ovarian morphology, with 7/29 women in the treatment group no longer displaying any polycystic ovaries, while another 5 women had improved down to only one polycystic ovary.

SUMMARY: VITAMIN D AND PCOS

In this study, vitamin D supplementation (50,000 IU/week) in obese women with PCOS, significantly decreased levels of total testosterone and increased SHBG, improving ovarian morphology and causing a return of regular menstrual cycles, in 92% of women who commenced treatment with irregular cycles.

Limitations

  1. Small sample size overall
  2. Lack of evaluation for other parameters, including free testosterone, FSH, LH, and AMH
  3. This study does not directly correlate Vitamin D intake with improved fertility outcomes
  4. Vitamin D intake in excess of upper safe limit

Funding

No external funding was declared for this study.

Glossary

Granulosa cells
A primary cell type within the ovary that provides the physical support and microenvironment needed for the developing oocyte.

Hirsutism
Male pattern hair growth.

Hyperandrogenism
High levels of androgens.

Hookah
An oriental tobacco pipe.

n
Sample size.

P-value
The probability that a result occurred by random chance.

Similar studies

Wehr E, et al. (2014). Effect of vitamin D3 treatment on glucose metabolism and menstrual frequency in polycystic ovary syndrome women: a pilot study. http://pubmed.ncbi.nlm.nih.gov/21613813/

Thys-Jacobs S, et al. (1999). Vitamin D and calcium dysregulation in the polycystic ovarian syndrome. http://pubmed.ncbi.nlm.nih.gov/10433180/


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