AD is a 21 year old female presenting with irregular periods, hair loss, acne, and excess weight. AD receives a diagnosis of polycystic ovarian syndrome (PCOS), prescriptions for oral contraceptives and metformin, and is advised to lose weight. PCOS is a multifactorial metabolic and endocrine disorder, resulting in hormonal imbalances and inflammation, with genetic and environmental components, manifesting largely due to lifestyle factors. There is no cure for PCOS, but symptoms are manageable. AD is fortunate enough to get an accurate diagnosis early, unlike most who find out when having difficulty conceiving. Nearly 50% of women with PCOS are misdiagnosed or undiagnosed, despite PCOS affecting an estimated 1 in 5 women. 50% of women with PCOS become diabetic or pre-diabetic before age 40. Women with PCOS are 3 times more likely to develop endometrial cancer, eating disorders, anxiety, and depression.(1)

Between 40-85% of women with PCOS are overweight. Losing weight improves symptoms but has proven to be extremely difficult. Excessive weight does not cause PCOS. Rather, hormone imbalances lead to weight gain. Most diets, weight loss pills, and workout regimens do not aid in sustaining weight loss. They can even cause weight gain, due to the added stress put onto the body. Improving the underlying imbalance aids in weight loss.

PCOS is the leading cause of infertility and contributes to miscarriage, gestational diabetes, and preeclampsia. Many women are on birth control for years without implementing lifestyle modifications. 

When ready to conceive, women stop birth control only to have irregular cycles return. With lifestyle changes, including sleep and stress management, diet, exercise, women with PCOS can have regular cycles with ovulation, improved fertility, and outcomes. 

Oral contraceptives can improve symptoms by decreasing elevated testosterone levels but do not treat the underlying hormone imbalance caused by insulin resistance. Metformin, berberine, and inositol can be used alone or adjunct to birth control, along with lifestyle changes to improve symptoms, treat the underlying insulin resistance and prevent development of other complications. 

Metformin, an affordable option, is often used off-label to improve insulin resistance, leading to lower levels of luteinizing hormone and androgen levels, weight loss, and regulated menstrual cycles. Metformin is also a favorable option for gestational diabetes. Many patients experience uncomfortable side effects of diarrhea, flatulence, stomach cramping, nausea, and vomiting.(2)

Berberine, a Chinese herb, works as an AMP-activated protein kinase (AMPK) activator to improve insulin resistance and lipid dysmorphia. Berberine does not have intolerable side effects like metformin. There is currently not enough evidence to support safe use in pregnancy. (3)

Inositol, a vitamin-like substrate found in fruits and beans, is made of myo-inositol (MI) and D-chiro-inositol (DCI), which are incorporated into cell membranes. Defects in processing leads to impaired insulin signaling, causing insulin resistance. Supplementing with inositols in the 40:1 (MI:DCI) ratio improves insulin resistance. Inositol is well tolerated and can safely be supplemented in pregnancy.(4,5)

AD returns a year later after implementing lifestyle modifications and switching from metformin to inositol. She has lost 20 lbs and seen improvements in her hair loss and acne. With information about her options, AD made informed choices with her doctor about how to manage her PCOS.

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References:

1. Patel S. Polycystic ovary syndrome (PCOS), an inflammatory, systemic, lifestyle endocrinopathy. J Steroid Biochem Mol Biol. 2018 Sep;182:27-36. doi: 10.1016/j.jsbmb.2018.04.008. Epub 2018 Apr 17. PMID: 29678491.
2. Legro RS, Arslanian SA, Ehrmann DA, Hoeger KM, Murad MH, Pasquali R, Welt CK; Endocrine Society. Diagnosis and treatment of polycystic ovary syndrome: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2013 Dec;98(12):4565-92. doi: 10.1210/jc.2013-2350. Epub 2013 Oct 22.
3. Rondanelli M, Infantino V, Riva A, Petrangolini G, Faliva MA, Peroni G, Naso M, Nichetti M, Spadaccini D, Gasparri C, Perna S. Polycystic ovary syndrome management: a review of the possible amazing role of berberine. Arch Gynecol Obstet. 2020 Jan;301(1):53-60. doi: 10.1007/s00404-020-05450-4. Epub 2020 Feb 14. PMID: 32060683; PMCID: PMC7028834.
4. Prabhakar P, Mahey R, Gupta M, Khadgawat R, Kachhawa G, Sharma JB, Vanamail P, Kumari R, Bhatla N. Impact of myoinositol with metformin and myoinositol alone in infertile PCOS women undergoing ovulation induction cycles – randomized controlled trial. Gynecol Endocrinol. 2021 Apr;37(4):332-336. doi: 10.1080/09513590.2020.1810657. Epub 2020 Sep 18. PMID: 32945218.
5. Fruzzetti F, Perini D, Russo M, Bucci F, Gadducci A. Comparison of two insulin sensitizers, metformin and myo-inositol, in women with polycystic ovary syndrome (PCOS). Gynecol Endocrinol. 2017 Jan;33(1):39-42. doi: 10.1080/09513590.2016.1236078. Epub 2016 Nov 3. PMID: 27808588.