By Sara Hover, RPh, FAARM, PCCA Clinical Compounding Pharmacist

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age world-wide.¹ The diagnostic criteria have changed over the last several years and vary a bit for adolescents.² Therapeutic options for PCOS include medication, achieving hormone balance and lifestyle management. Treatment goals address the most prominent symptoms, including hirsutism, infertility and acne as well other issues related to insulin resistance.¹ Recently, links have been made between PCOS, hypothyroidism,³ periodontal disease⁴ and low vitamin D levels.⁵

I covered hirsutism in my blog post “ An Innovative Option for Hirsutism: Topical Meformin ,” so here I will discuss other comorbidities that can be addressed to help this patient population. The complicated pathophysiology of PCOS, which intertwines epigenetics and environmental factors, has yet to be completely illuminated. Current treatment revolves around managing symptoms.

Hormone Balance

Women with PCOS have many anovulatory cycles resulting in lower progesterone production. This lack of progesterone production creates an imbalance between estrogen and progesterone, resulting in endometrial hyperplasia, a condition where the endometrium becomes excessively thick. Women with PCOS-induced endometrial hyperplasia are more likely than women without PCOS to develop endometrial carcinoma.⁶ Therefore, it is prudent to monitor hormone levels and create proper balance between estradiol and progesterone. Life is about balance, after all. There are some studies showing that women with PCOS have an insensitivity to progesterone associated with elevated fasting insulin.⁷ Therefore, reducing insulin levels will promote progesterone functionality. This is just another example of the intertwining of the systems of the body.

Insulin Resistance

Insulin resistance is the most prominent metabolic consequence for PCOS patients, affecting nearly 70% of this population. When the insulin receptor is unresponsive to insulin, higher amounts of this hormone are required to send the same message. This results in increased production and release of insulin. Hyperinsulinemia (abnormally high blood insulin level) and insulin resistance are both also seen in lean PCOS patients, not just obese patients.⁸ Excess insulin can contribute to excess androgen production by direct stimulation of the ovarian theca cells. Hyperinsulinemia also leads to higher free testosterone by suppressing sex hormone binding globulin.⁹ Treating insulin resistance with medication and lifestyle changes can therefore have an incredible impact on PCOS.

Metformin has emerged as the prominent treatment choice in PCOS to reduce insulin resistance and lower insulin levels. The major drawback with metformin is the gastrointestinal side effects with the oral dosage form, including diarrhea, nausea, indigestion and abdominal pain.¹⁰ An alternative delivery method to avoid the stomach would be permeation-enhanced topical or vaginal administration. Pharmacy compounding may be a good choice in these instances where patients need customized medication options in various dosage forms.

Hypothyroidism

Subclinical hypothyroidism is frequently detected in PCOS patients. One of the cross functions of thyroid hormones is to act as an insulin agonist in muscle tissue and insulin antagonist in the liver. Therefore, if thyroid hormone is low, there would be an effect on glucose utilization and production. Thyroid hormone replacement in PCOS patients may also lead to a reduction in serum androgen level. In fact, some authors have considered insulin resistance to result from hypothyroidism.³ It could be hypothesized that the increased rate of infertility in PCOS could also be linked to decreased thyroid hormones. Finding the right balance of thyroid hormones can be tricky, though. Custom formulations of T4 (levothyroxine sodium) and T3 (liothyronine) or porcine thyroid hormone provide another tool in the prescriber’s toolbox to meet individual patient needs, and this is another particular area where pharmacy compounding may be able to help.

Periodontal disease

A recent review correlated a link between PCOS and periodontal disease, which is a chronic inflammatory condition that can cause destruction of the tissue that surrounds teeth.⁴ The risk of PCOS patients developing periodontal disease is inconclusive, but it is worth it for practitioners to be aware of the correlation. Dentists should be aware and monitor their patients for possible PCOS, and practitioners treating PCOS should question patients on their dental health. There are several dental preparations that can reduce gum inflammation and promote healing for gingival disease.

Vitamin D3

The relationship between vitamin D and PCOS is controversial but interesting. Current literature recognizes that Vitamin D is a hormone and is instrumental in immune system function while playing a role with certain disease states, such as Type 2 diabetes, cardiovascular disease and cancer. ^5,11 An underlying issue of all those disease states as well as PCOS is inflammation. Vitamin D has shown to inhibit the release of inflammatory cytokines, thereby reducing inflammation. Many observational studies have demonstrated that PCOS patients with a low vitamin D level had increases in body mass index, insulin resistance, testosterone and dehydroepiandrosterone.⁵ This information provides an opportunity for pharmacists to educate patients while providing a quality vitamin D3 supplement. Working with patients and providers to optimize vitamin D3 levels may therefore play a critical role in helping PCOS patients.

Many of the potential treatment options I’ve discussed in this article are specifically relevant to pharmacy compounding. Balancing hormones, compounding prescriptions in alternative dosage forms when commercial products do not meet patient needs, and helping them achieve optimal nutrition and lifestyle choices are all advantages of prescribers and patients working closely with compounding pharmacists. Pharmacies looking for supplements to offer their patients might consider Wellness Works, which carries professional-grade vitamin D3 softgels (5,000 IU). PCCA members with Clinical Services access can also find some examples of commonly requested compounding formulas in our database that may be relevant to discuss with practitioners concerning these patients. If they have questions about compounding for patients with PCOS, they can contact our clinical compounding pharmacists at 800.331.2498.

Sara Hover, RPh, FAARM, has been a compounding pharmacist for over 20 years and joined the PCCA Clinical Services team in June 2013. Before joining the PCCA staff, she was the owner and pharmacist of Creative Compounds in Prosper, Texas, an independent, compounding-only pharmacy that focused on women’s health and nutrition. In addition to her expertise in hormone replacement therapy, Sara possesses a vast knowledge of homeopathics as well as herbal and vitamin supplements. Sara obtained her Bachelor of Science degree from the University of Texas at Austin in 1994. She is a lifetime member of the University of Texas College of Pharmacy Alumni Association.

Photo by Clarisse Meyer on Unsplash.

References

1. Witchel, S. F., Oberfield, S. E., & Peña, A. S. (2019). Polycystic ovary syndrome: Pathophysiology, presentation, and treatment with emphasis on adolescent girls. Journal of the Endocrine Society, 3 (8), 1545–1573. https://doi.org/10.1210/js.2019-00078

2. Tehrani, F. R., & Amiri, M. (2019). Polycystic ovary syndrome in adolescents: Challenges in diagnosis and treatment.International Journal of Endocrinology & Metabolism, 17(3). https://dx.doi.org/10.5812%2Fijem.91554

3. Fatima, M., Amjad, S., Ali, H. S., Sr., Ahmed, T., Kahn, S., Raza, M., & Inam, M. (2020). Correlation of subclinical hypothyroidism with polycystic ovary syndrome (PCOS). Cureus, 12(5). https://dx.doi.org/10.7759%2Fcureus.8142

4. Machado, V., Escalda, C., Proença, L., Mendes, J. J., & Botelho, J. Is there a bidirectional association between polycystic ovarian syndrome and periodontitis? A systematic review and meta-analysis. Journal of Clinical Medicine, 9(6). https://dx.doi.org/10.3390%2Fjcm9061961

5. Wang, L., Lv, S., Li, F., Yu, X., Bai, E., & Yang, X. (2020). Vitamin D deficiency is associated with metabolic risk factors in women with polycystic ovary syndrome: A cross-sectional study in Shaanxi China. Frontiers in Endocrinology, 11. https://dx.doi.org/10.3389%2Ffendo.2020.00171

6. Li, X., Feng, Y., Lin, J.-F., Billig, H., & Shao, R. (2014). Endometrial progesterone resistance and PCOS. Journal of Biomedical Science, 21(1). https://dx.doi.org/10.1186%2F1423-0127-21-2

7. Blank, S. K., McCartney, C. R., Chhabra, S., Helm, K. D., Eagleson, C. A., Chang, R. J., & Marshall, J. C. (2009). Modulation of gonadotropin-releasing hormone pulse generator sensitivity to progesterone inhibition in hyperandrogenic adolescent girls — Implications for regulation of pubertal maturation.The Journal of Clinical Endocrinology & Metabolism, 94(7), 2360–2366. https://doi.org/10.1210/jc.2008-2606

8. Sanchez-Garrido, M. A., & Tena-Sempere, M. (2020). Metabolic dysfunction in polycystic ovary syndrome: Pathogenic role of androgen excess and potential therapeutic strategies. Molecular Metabolism, 35. https://doi.org/10.1016/j.molmet.2020.01.001

9. Marshall, J. C., & Dunaif, A. (2012). Should all women with PCOS be treated for insulin resistance? Fertility and Sterility, 97(1), 18–22. https://doi.org/10.1016/j.fertnstert.2011.11.036

10. Metformin. (2020). In Clinical Pharmacology. Retrieved from http://clinicalpharmacology-ip.com/Forms/drugoptions.aspx?cpnum=379&t=0

11. Norman, A. W. (2008). From vitamin D to hormone D: Fundamentals of the vitamin D endocrine system essential for good health. The American Journal of Clinical Nutrition, 88(2), 491S–499S. https://doi.org/10.1093/ajcn/88.2.491S

These statements are provided for educational purposes only. They have not been evaluated by the Food and Drug Administration, and are not to be interpreted as a promise, guarantee or claim of therapeutic efficacy or safety. The references cited did not necessarily evaluate PCCA products or formulas included in these statements. The information contained herein is not intended to replace or substitute for conventional medical care, or encourage its abandonment.