Ovarian Wellness Protocol: A Resource for Practitioners


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by Fullscript’s Integrative Medical Advisory Team

Polycystic ovary syndrome (PCOS), also known as hyperandrogenic anovulation (HA) or Stein–Leventhal syndrome, is one of the most common endocrine disorders affecting women of reproductive age. (3)(10) It is estimated that PCOS affects 4-10% of women of reproductive age worldwide, (3)(6) placing a significant burden on the healthcare system. In the United States, PCOS affects approximately five million women and the cost of screening and treating PCOS-related conditions is an estimated four billion dollars annually. (3)(12)

woman holding her stomach laying on couch

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders affecting women of reproductive age.

What is polycystic ovary syndrome (PCOS)?

PCOS is a complex endocrine disorder that involves excess androgen (hyperandrogenism), menstrual irregularity, and/or polycystic ovaries. (3)(12) PCOS is typically characterized by high circulating levels of certain hormones (e.g., testosterone, androstenedione, luteinizing hormone), as well as 12 or more follicles between 2-9mm in diameter in each ovary and/or an ovarian volume exceeding 10ml. (3)

The clinical presentation of PCOS may vary, however the Rotterdam criteria, one set of guidelines for PCOS diagnosis, divides the condition into the following four phenotypes:

  • Frank or classic polycystic ovary PCOS: characterized by hyperandrogenism, polycystic ovaries, chronic anovulation, and poor metabolic and cardiovascular risk factor profiles (e.g., insulin resistance, lipid profile) compared to non-classic phenotype
  • Classic non-polycystic ovary PCOS: characterized by hyperandrogenism and chronic anovulation, but ovaries are normal/non-polycystic
  • Non-classic ovulatory PCOS: characterized by hyperandrogenism and polycystic ovaries, but menstrual cycles are regular
  • Non-classic mild or normoandrogenic PCOS: characterized by chronic anovulation and polycystic ovaries, but androgens are normal (3)

The table below provides an overview of the clinical presentation of the four PCOS phenotypes.

The Rotterdam criteria divides PCOS into four phenotypes based on clinical presentation.

Signs, symptoms, and comorbidities

PCOS typically presents with a variety of symptoms associated with excess androgen and menstrual dysfunction, (3) including:

  • Anovulation (10)
  • Acanthosis nigricans
  • Oligomenorrhea (3)(12)
  • Amenorrhea
  • Hirsutism
  • Acne (3)(10)(12)
  • Androgenetic alopecia (3)
  • Skin tags
  • Alopecia
  • Pelvic pain (12)

Symptoms often differ by age; young women typically present with reproductive and psychological problems, while older women predominantly experience metabolic symptoms. (3)

woman looking at her skin in mirror

Symptoms of PCOS may include hirsutism, alopecia, acne, and skin tags.

PCOS also increases the risk of developing several other health conditions, including:

  • Infertility or subfertility (3)(6)(12)
  • Dyslipidemia (12)
  • Type II diabetes
  • Cardiovascular disease (CVD) (3)(10)(12)
  • Insulin resistance (3)(10)
  • Obesity
  • Cancer (e.g., endometrial) (3)(12)
  • Psychological disorders (e.g., depression, anxiety, substance abuse, disordered eating, psychosexual dysfunction) (3)(6)
  • Fatty liver
  • Metabolic syndrome
  • Sleep apnea (6)

Causes and risk factors

PCOS involves dysfunctions in ovarian function, insulin metabolism, and hypothalamic–pituitary axis function. While the cause of PCOS is unknown, the condition is believed to develop as a result of a combination of genetic and environmental factors. (6)(12) Some identified risk factors include:

  • Family history (6)(12)
  • Diabetes and insulin resistance (6)(12)
  • Obesity (6)(12)
  • Inactivity, sedentary lifestyle (6)
  • Poor dietary choices (12)
  • Infectious agents and toxins (12)

Integrative protocol for ovarian wellness

PCOS treatment typically involves the collaboration of an interdisciplinary team and a combination of lifestyle (e.g., diet, exercise) and pharmaceutical interventions (e.g., insulin-sensitizing agents). Commonly prescribed medications include metformin, thiazolidinediones, and spironolactone. (3) Certain dietary supplements have also been shown to be effective in supporting treatment of PCOS.

Berberine

Berberine is the primary active component of several medicinal herbs, including Berberis vulgaris (barberry), Coptis chinensis (Chinese goldthread), Phellodendron amurense (Amur corktree), and Hydrastis canadensis (goldenseal). (10)(12) Berberine has been used traditionally in the treatment of a number of conditions, including gastrointestinal conditions (e.g., diarrhea), metabolic conditions, and infertility. Recently, berberine been used to enhance the effectiveness of certain medications, namely cyproterone acetate (CPA), clomiphene (CC), and letrozole (LET). Berberine supplementation has also been shown to reduce insulin resistance (10) and improve cholesterol levels. (14)

Research findings:

  • Reductions in total testosterone, free androgen index, fasting glucose, fasting insulin and HOMA-IR, and increases in SHBG. (1)
  • Decreases in BMI, lipid parameters and total FSH requirement, and an increase in live birth rate with fewer gastrointestinal adverse events. (1)
  • Decrease 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. (15)

US: Search for Berberine in the Fullscript catalog.
CAN: Search for Berberine in the Fullscript catalog.

myo-inositol extract on wooden spoon

D-chiro-inositol and myo-inositol play an important role in maintaining normal levels of insulin and FSH.

D-chiro-inositol and myo-inositol

An important component of cell membranes, D-chiro-inositol (DCI) and myo-inositol (MI) are the two most abundant inositols of the inositol stereoisomer family. MI and DCI are found abundantly in nature, particularly in fruit and beans. The effectiveness of MI and DCI in PCOS is believed to be attributed to their role in ovarian function and in maintaining normal levels of hormones, such as insulin and follicle-stimulating hormone (FSH). Imbalances or deficiencies in MI and DCI have been shown to contribute to PCOS. Therefore, correcting these imbalances through supplementation may help address features and symptoms of the condition. (9)

Research findings for DCI:

  • Improved the regularity of the menstrual cycle, the Acne Score, the endocrine and metabolic parameters and the insulin-resistance (5)
  • Effective in improving ovarian function and metabolism in patients with PCOS, and reduced hyperandrogenism better (13)

US: Search for D-Chiro-Inositol in the Fullscript catalog.
CAN: Search for D-Chiro-Inositol in the Fullscript catalog.

Research findings for MI:

  • Significantly decreased serum total testosterone, modified Ferriman-Gallwey (mF-G) scores and serum high-sensitivity C-reactive protein (hs-CRP) levels (7)
  • Meta-analysis demonstrates that myo-inositol improves HOMA index and increases the E2 (estradiol) level (16)

US: Search for Myo-Inositol in the Fullscript catalog.
CAN: Search for Myo-Inositol in the Fullscript catalog.

Chromium picolinate

Chromium is a trace mineral found in small amounts in a wide variety of dietary sources, including meat, whole grains, and some vegetables, fruit, and spices. Unfortunately, dietary intake of chromium is difficult to determine as it is significantly affected by agricultural and manufacturing processes. Chromium is found in two primary forms, biologically active trivalent chromium found naturally in food and toxic hexavalent chromium, a bi-product of industrial pollution. (11) Trivalent chromium (Cr3+) can also be obtained in various supplemental forms, the most popular being chromium picolinate which contains 12.4% elemental trivalent chromium. (2) Chromium has been shown to improve insulin sensitivity, (8) BMI, testosterone concentrations, cardiometabolic risk factors, and oxidative stress in cases of PCOS. (4)

Research findings:

  • Demonstrated 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 (8)
  • Significantly decreased serum triglycerides, VLDL and total cholesterol concentrations
  • Contributes to increases in plasma total antioxidant capacity and a significant reduction in malondialdehyde values (8)
  • Overall reduction in BMI and free testosterone concentration (4)

US: Search for Chromium Picolinate in the Fullscript catalog.
CAN: Search for Chromium Picolinate in the Fullscript catalog.

The bottom line

PCOS is a complex endocrine disorders commonly treated with lifestyle and pharmaceutical interventions. Research has shown that certain dietary supplements, including berberine, D-chiro-inositol, myo-inositol, and chromium, may be beneficial for individuals with PCOS.
A protocol using natural supplements can be used therapeutically on its own or as an adjunct to existing treatment. If you are not an integrative healthcare provider, we recommend speaking with one to learn whether these supplements are ideal for your wellness plan.

If you are a practitioner, consider signing up to Fullscript. If you are a patient, talk to your healthcare practitioner about Fullscript!

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Disclaimer

The Fullscript 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 adding this protocol to your Fullscript template library, you understand and accept that the recommendations in the protocol are for initial guidance and may not be appropriate for every patient.

  1. An, Y., Sun, Z., Zhang, Y., Liu, B., Guan, Y., & Lu, M. (2014). The use of berberine for women with polycystic ovary syndrome undergoing IVF treatment. Clinical Endocrinology, 80(3), 425-31.
  2. Ashoush, S., Abou‐Gamrah, A., Bayoumy, H., & Othman, N. (2016). Chromium picolinate reduces insulin resistance in polycystic ovary syndrome: Randomized controlled trial. The Journal of Obstetrics and Gynaecology Research, 42(3), 279-285.
  3. El Hayek, S., Bitar, L., Hamdar, L. H., Mirza, F. G., & Daoud, G. (2016). Polycystic ovarian syndrome: An updated overview. Frontiers in Physiology, 7, 124.
  4. Fazelian, S., Rouhani, M.H., Bank, S.S., & Amani, R. (2017). Chromium supplementation and polycystic ovary syndrome: A systematic review and meta-analysis. Journal of Trace Elements in Medicine and Biology, 42, 92-96.
  5. Formuso, C., Stracquadanio, M., & Ciotta, L. (2015). Myo-inositol vs. D-chiro inositol in PCOS treatment. Minerva Ginecologica, 67(4), 321-5.
  6. Genetics Home Reference. (2019). Polycystic ovary syndrome. Retrieved from https://ghr.nlm.nih.gov/condition/polycystic-ovary-syndrome
  7. Jamilian, M., Farhat, P., Foroozanfard, F., Afshar Ebrahimi, F., Aghadavod, E., Bahmani, F., … Asemi, Z. (2017). Comparison of myo-inositol and metformin on clinical, metabolic and genetic parameters in polycystic ovary syndrome: A randomized controlled clinical trial. Clinical Endocrinology, 87(2), 194-200.
  8. Jamilian, M., Zadeh Modarres, S., Amiri Siavashani, M., Karimi, M., Mafi, A., Ostadmohammadi, V., & Asemi, Z. (2018). The influences of chromium supplementation of glycemic control, markers of cardio-metabolic risk, and oxidative stress in infertile polycystic ovary syndrome women candidate for in vitro fertilization: A randomized, double-bling, placebo-controlled trial. Biological Trace Element Research, 185(1), 48-55.
  9. Kalra, B., Kalra, S., & Sharma, J. B. (2016). The inositols and polycystic ovary syndrome. Indian Journal of Endocrinology and Metabolism, 20(5), 720–724.
  10. Li, M., Zhou, X., & Li, X. (2018). The effect of berberine on polycystic ovary syndrome patients with insulin resistance (PCOS-IR): A meta-analysis and systematic review. Evidence-Based Complementary and Alternative Medicine.
  11. National Institutes of Health. (2019). Chromium. Retrieved from https://ods.od.nih.gov/factsheets/Chromium-HealthProfessional/
  12. Ndefo, U. A., Eaton, A., & Green, M. R. (2013). Polycystic ovary syndrome: A review of treatment options with a focus on pharmacological approaches. Pharmacy & Therapeutics, 38(6), 336–355.
  13. Pizzo, A., Laganà, A., & Barbaro, L. (2014). Comparison between effects of myo-inositol and D-chiro-inositol on ovarian function and metabolic factors in women with PCOS. Gynecological Endocrinology, 30(3), 205-8.
  14. Wang, Y., & Zidichouski, J. A. (2018). Update on the benefits and mechanisms of action of the bioactive vegetal alkaloid berberine on lipid metabolism and homeostasis. Cholesterol, 2018, 7173920.
  15. Wei, W., Zhao, H., Wang, A., Sui, M., Liang, K., Deng, H. , … Guan, Y. (2012). A clinical study on the short-term effect of berberine in comparison to metformin on the metabolic characteristics of women with polycystic ovary syndrome. European Journal of Endocrinology, 166(1), 99-105.
  16. Zeng, L., & Yang, K. (2018). Effectiveness of myoinositol for polycystic ovary syndrome: A systematic review and meta-analysis. Endocrine, 59(1), 30-38.