Mar 30, 2022

Disclaimer 

Our Integrative Medical Advisory team has developed or collected these protocols from practitioners and supplier partners to help health care practitioners make decisions when building treatment plans. By following this protocol, you understand and accept that the recommendations in the protocol are for initial guidance and need to seek medical professional advise.

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Ovarian Wellness​

Optimal ovarian wellness may include management of reproductive hormonal or endocrine disorders such as polycystic ovarian syndrome (PCOS), which is reported to affect approximately 6% to 10% of women. (3) PCOS affects multiple systems, causing problems with reproductive, metabolic, and psychological factors. Reproductive issues such as infertility, adverse pregnancy outcomes, and endometrial cancer are all possibilities. Metabolic factors and possible comorbidities include obesity, type 2 diabetes mellitus, insulin resistance, and metabolic syndrome. (11) 

Due to the system-wide nature of PCOS, the intervention targets need to have a similar approach. Common therapies such as pharmaceutical hormone regulation are used in many PCOS patients, as well as metformin for the metabolic aspects. 

The protocol presented below aims to address different aspects of the root causes for women suffering from PCOS.

Omega-3 with Vitamin E

1000 mg of omega-3 with 400 IU vitamin E (8)(22)

  • Insulin resistance decreased as shown by improvements in homeostasis model of insulin resistance (HOMA), decreased insulin, and increased quantitative insulin sensitivity check index; additionally, total and free testosterone improved compared to placebo when given 1000 mg omega-3 fatty acids from flaxseed oil containing 400 mg α-Linolenic acid and 400 IU vitamin E supplements (8)
  • Obese and/or overweight women with PCOS demonstrated increased total antioxidant capacity, catalase activity, and glutathione levels as well as decreased malondialdehyde concentration compared to placebo when given 2 g of omega-3 with 400 IU of vitamin E (23)
  • Gene expression, lipid profile, and oxidative stress all improved as shown by downregulated expressed levels of Lp(a) mRNA and Ox-LDL mRNA in peripheral blood mononuclear cells, decreased serum triglycerides, VLDL, total, LDL, and total/HDL, and increased plasma total antioxidant capacity, decreased malondialdehyde levels compared to placebo when supplemented for 12 weeks (22)
  • PCOS patients improved gene expression as shown by upregulated peroxisome proliferator-activated receptor gamma (PPAR-γ) and mRNA in peripheral blood mononuclear cells and downregulated expressed levels of oxidized low-density lipoprotein receptor (LDLR) mRNA in peripheral blood mononuclear cells compared to placebo when given 1000 mg omega-3 fatty acids from flaxseed oil containing 400 mg α-linolenic acid  for 12 weeks (18)
  • Systematic review and meta-analysis of 9 trials found omega-3 fatty acids may improve insulin resistance in patients with PCOS (26) 
Omega-3

Vitamin D

50,000 IU once per week, or once every other week, for a minimum of 8 weeks (7)(24) or 1000 IU per day for a minimum of 12 weeks (14) 

  • When given 50,000 IU once per week, insulin sensitivity improved in IVF candidates with PCOS as demonstrated by decreased insulin and HOMA for insulin resistance (HOMA-IR) compared to placebo; additionally, a decrease in serum anti-Müllerian hormone (AMH) was observed (7)
  • In a systematic review of 11 studies, it was found that continuous supplementation of vitamin D up to 4000 IU per day was associated with improved insulin sensitivity and HOMA-IR (16)
  • When comparing vitamin D, placebo, or metformin in the treatment of PCOS, a systematic review and meta-analysis of 9 studies found both metformin and vitamin D individually improved follicular development, while metformin with vitamin D had more pronounced improvements on menstrual cycle regulation (9)
  • PCOS patients deficient in vitamin D (as defined by a plasma 25-OH vitamin D <20 ng/mL) had decreased fasting plasma glucose and increased HOMA for B-cell function, adiponectin, and serum vitamin D when supplemented 50,000 IU once per week for 8 weeks compared to placebo (24)
  • When comparing doses of 4,000 IU per day, 1000 IU per day, or placebo, high dose vitamin D had the most pronounced decreases in total testosterone, free androgen index (FAI), hirsutism, and high-sensitivity CRP, and elevations of sex hormone-binding globulin (SHBG) and total antioxidant capacity in insulin-resistant PCOS patients (14)
Vitamin D

Berberine

500 mg per day, for a minimum of 3 months (5)

  • Infertile women with PCOS undergoing IVF experienced decreased total testosterone, free androgen index, fasting glucose, fasting insulin and HOMA-IR, BMI, lipid parameters and total FSH requirement, and an increase in live birth rate and SHBG when given berberine or metformin in comparison to placebo; additionally fewer gastrointestinal adverse events were observed in the berberine group and was superior for live birth weight, lipid parameters, and total FSH compared to metformin (1) 
  • Berberine with cyproterone acetate lead to decreases in the waist circumference and waist-to-hip ratio, total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol, as well as increase in high-density lipoprotein cholesterol (HDLC) and sex hormone-binding globulin in women with PCOS and insulin resistance compared to metformin and cyproterone acetate group and placebo group (25)  
  • In a meta-analysis and systematic review of 9 randomized controlled trials, berberine was found to be comparable to metformin as demonstrated by no significant differences found between them in alleviating insulin resistance, improving glycolipid metabolism or reproductive endocrine condition (17)
  • Lipid metabolism improved as shown by improved BMI, HOMA index, FPG, LDL-C, HDL-C, TG, hsCRP in women with and without PCOS who had oral contraceptive induced hypercholesterolemia (5) 
Berberine

Chromium Picolinate

200 µg, per day, minimum 8 weeks (12)(13)

  • Improved glycemic control as demonstrated by  significant reductions in fasting plasma glucose, insulin levels, homeostatic model of assessment for insulin resistance, and a significant increase in quantitative insulin sensitivity check index; improved cardio-metabolic risk demonstrated by decreased serum triglycerides, VLDL and total cholesterol concentrations (15)
  • A systematic review and meta-analysis of 7 randomized controlled trials found overall reductions in BMI, fasting insulin, and free testosterone concentration (10) 
  • When given 1000 μg CrP for 6 months, PCOS patients experienced decreased BMI and FSI, as well as increased chance of ovulation and regular menstruation after five months of treatment compared to placebo (2)
  • Improved metabolic profile as demonstrated by decreased serum insulin levels, HOMA-IR, HOMA-B (beta cell function) and increase in quantitative insulin sensitivity check index (QUICKI) score compared to placebo (12)
  • Improved pregnancy rate by 16.7% compared to 3.3% in placebo, decreased prevalence of acne by 20.0 compared to 3.3% in placebo; additionally, chromium improved oxidative stress as shown by increased total antioxidant capacity and decreased hirsutism, serum hsCRP, plasma MDA (malondialdehyde) (13)
Chromium Picolinate

Inositol

1-2 g inositol (myo-inositol and d-chiro-inositol), minimum 3 months (6)(19)(21)

  • In a meta-analysis, myoinositol was found to improve the homeostatic model assessment (HOMA), increase total testosterone and estradiol, and alleviate insulin resistance (27)
  • Women with PCOS given 1200 mg of d-chiro-inositol twice daily experienced improved insulin sensitivity as measured by oral glucose tolerance test (4)
  • When comparing 6 months of supplementation with 4g of myo-inositol(MI) or 1g of d-chiro-inositol(DCI), both therapies improved ovarian and metabolic functions; however, myoinositol was superior for metabolic function and di-chiro-inositol was superior in decreasing hyperandrogenism (21)
  • Patients given 2g of inositol twice per day for 3 months at a variety of myo-inositol (MI) to d-chiro-inositol (DCI) ratios, it was found that the 40:1 MI/DCI ratio was ideal for restoring and normalizing ovulation in PCOS patients (19)
  • Women with PCOS undergoing IVF-ET demonstrated higher pregnancy rates and improved quality of oocytes and embryos when treated with the combination therapy of 1.1 g of MI with 27.6 mg of DCI compared to 500 mg of DCI only (6)
  • When comparing MI with DCI versus MI alone for 6 months of treatment, both groups had pronounced improvements; however combined MI and DCI was more effective after 3 months of treatment (20)
Inositol

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