5 Prescriptions for PCOS You Didn’t Learn About in Med School 

by Krista Russ

Alongside lifestyle interventions like diet, exercise, and evidence-supported supplements, prescription medications and other pharmaceutical-grade compounds can be a powerful, often necessary addition for managing PCOS in your patients.   

Whether your patients are battling infertility, fighting bothersome secondary effects like hirsutism and weight gain, or want to prevent long-term complications like heart disease and diabetes, pharmaceuticals have an important place in your PCOS toolkit.

The Conventional Approach  

Naltrexone (not to be confused with low dose naltrexone/LDN)

As you probably recall from your clinical experience, naltrexone is used primarily to combat opioid and alcohol addiction. You might be wondering what a medication used for drug addiction has to do with PCOS? Well, it turns out that naltrexone has been shown to reduce fasting insulin levels, lower inflammation, and reduce cravings in several studies [1]. This has direct implications for PCOS, which causes hyperinsulinemia, low-grade inflammation, as well as powerful sugar cravings.   

Naltrexone also blocks the opioid receptor which has recently been implicated in promoting hyperinsulinemia. It appears that women with PCOS may have increased exogenous opioid production, which is known to stimulate insulin release [1],[2], [3].   

Naltrexone takes the edge off cravings for sugary foods by modulating the brain’s reward system, leading to weight loss and improvements in insulin sensitivity, especially when combined with bupropion–such as in the weight-loss medication Contrave [4], [5]. For example, in one study [4], 50 mg per day for 6 months reduced BMI by nearly 5 points in patients, equivalent to an impressive weight loss of 24 pounds.  

In another 12-week double blind study [2], 75 mg of Naltrexone per day reduced fasting insulin and C-peptide (a component of proinsulin) levels by a stunning 40 percent and 50 percent respectively.  

Lastly, naltrexone is affordable for most patients. It is available for as low as 15 USD with some savings coupon programs–even without insurance. It also has very few side effects and is generally well tolerated. All of that makes Naltrexone a winning drug for PCOS management when prescribed off-label.   

Metformin + GLP1 Agonist

This regime involves a combination of two medications taken together to complement one another. As you likely know, metformin is a weight-neutral, insulin-sensitizer and first line therapy for both PCOS and type two diabetes. Metformin works in many ways, including by reducing gluconeogenesis, improving insulin sensitivity, and increasing the nutrient sensor AMPK, which increases glucose uptake by cells [6].  

Metformin has been shown to regulate cycles, reduce secondary effects like facial hair, and even improve conception rates [7] [8] [9]. Whether or not it reduces long-term complications like diabetes is iffy at best–especially without lifestyle changes–and it is notorious for unpleasant GI side effects like gas and bloating. For most, these effects are fleeting, but not everyone–especially when taken at a higher dose (over 1,000 mg per day). It is affordable at least.   

Metformin is even more powerful when combined with Liraglutide (brand name Victoza), especially for weight loss, which can greatly improve PCOS and sometimes help infertility when there is no male factor present and PCOS is the only gynecological issue preventing pregnancy [10]. Victoza is a GLP1 agonist and works by increasing incretins–gut hormones that slow stomach emptying and relay sensations of fullness to the brain.   

However, Liraglutide has not been studied in pregnancy and should not be taken during gestation when weight gain is essential. Victoza, along with the other GLP1 agonist– Semaglutide–also bears an extremely expensive price tag, upwards of 1500 USD per month depending on the supplier and is typically not covered by insurance. Fortunately, there are online savings/coupon programs that offer a significantly reduced price to your patients who cannot afford it. Like Metformin, GLP1 agonists also cause nausea. In fact, the nausea and resulting lack of appetite is likely why it’s so effective for weight loss.   

Bioidentical Progesterone

Progesterone is considered the hormone of pregnancy, which is certainly true, but its importance extends far beyond pregnancy. Progesterone opposes estrogen. Where estrogen promotes growth, progesterone curbs it, so that things don’t get out of hand. Unfortunately, women with PCOS tend to make too little progesterone, putting them at an elevated risk of cancers such as endometrial and breast. Progesterone supplementation can easily prevent this.   

Progesterone also raises the metabolic rate, promotes restful sleep, and eases anxiety and postpartum depression–all good news for your PCOS patients, who are at an increased risk for anxiety and depression [11]. As many as 50 percent suffer from depression [12].  

Finally, progesterone is critical to maintaining a pregnancy since it thickens the uterine lining and supplies a growing embryo with nutrients. Without it, the lining is too thin, and miscarriage is inevitable. As a result, women with PCOS often have repeated miscarriages that are easily preventable.   

In order to reap the full benefits, your patients need bioidentical progesterone, especially micronized compounded progesterone—a highly absorbable form—as opposed to synthetic progesterone (Provera) or a lower quality, non-compounded bioidentical progesterone like Prometrium. Bioidentical progesterone is structurally identical to what the human body makes and proven safe by many studies, but synthetic progesterone (progestin) is derived from horses and has potential for devastating health effects like blood clots and strokes, which PCOS patients are already at increased risk for.   

To learn how to prescribe progesterone for PCOS, be sure to sign up for Part One BHRT training conference which takes place November 10-12, 2023.  

Desiccated Thyroid Extract

Research shows that patients with PCOS are more prone to thyroid disturbances, especially of autoimmune origin such as Hashimoto’s Thyroiditis, as evidenced by the presence of anti-TPO antibodies, per a 2016 paper [13] linking PCOS to autoimmune disorders.  

PCOS patients are known to have a significantly reduced basal metabolic rate even when Body Mass Index (BMI) is taken into account by over 400 k calories per day [14] [15].This is likely due to hyperinsulinemia which drives fat storage and inhibits lipolysis by preventing the liberation of free fatty acids.  

For example, type 2 diabetic patients treated with insulin are known to have a reduction in metabolic rate [16]. And as early as 1912, Elliot P Joslin–a physician–and Francis G Benedict–a chemist–each famous for their work in endocrinology and metabolism, noted a 15 percent increase in the metabolic rate of untreated, insulin-deficient diabetics compared to their normal-insulin peers of a similar body weight [16]. 

Since thyroid hormone increases the metabolic rate, it is not illogical to deduce that exogenous thyroid supplementation would benefit PCOS, especially as inadequate thyroid function is notoriously linked to insulin resistance, dyslipidemia, and metabolic syndrome–all complications that characterize PCOS and its long-term complications [17]. Hypothyroidism only exacerbates PCOS by attenuating insulin sensitivity. 

Aside from its role in maintaining a healthy metabolic rate, thyroid hormone directly impacts the menstrual cycle and reproductive hormones like estrogen and progesterone, so low levels can interfere with their intricate balance, further reducing fertility and/or increasing risk for miscarriage [18].  

To learn how to prescribe thyroid for PCOS, be sure to sign up for Part One BHRT training conference which takes place November 10-12, 2023.  

The Bottom Line

When considering adding pharmaceuticals to your PCOS medical toolkit, bear in mind that no medication will override a poor diet or sedentary lifestyle–rather pharmaceuticals can augment your patients’ healthy lifestyle and help them power past obstacles when lifestyle changes are insufficient.  

For more on drugs and bioidentical hormones–including the optimal dose to give–and other tools for managing PCOS in your patients like helpful diagnostic tools, be sure to download our EBook: Your Ultimate PCOS Toolkit

References  

1. Duleba AJ. Medical management of metabolic dysfunction in PCOS. J Steroids. 2012 Mar 10;77(4):306-11. doi: 10.1016/j.steroids.2011.11.014. Epub 2011 Dec 13. PMID: 22182833; PMCID: PMC3409585. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3409585/  
2. Sir-Petermann T, López G, Castillo T, Calvillán M, Rabenbauer B, Wildt L. Naltrexone effects on insulin sensitivity and insulin secretion in hyperandrogenic women. J Exp Clin Endocrinol Diabetes. 1998;106(5):389-94. doi: 10.1055/s-0029-1212004. PMID: 9831304. https://pubmed.ncbi.nlm.nih.gov/9831304/ 
3. Eyvazzadeh AD, Pennington KP, Pop-Busui R, Sowers M, Zubieta JK, Smith YR. The role of the endogenous opioid system in polycystic ovary syndrome. J Fertil Steril. 2009 Jul;92(1):1-12. doi: 10.1016/j.fertnstert.2009.05.012. PMID: 19560572. https://pubmed.ncbi.nlm.nih.gov/19560572/ 
4. Fruzzetti F, Bersi C, Parrini D, Ricci C, Genazzani AR. Effect of long-term naltrexone treatment on endocrine profile, clinical features, and insulin sensitivity in obese women with polycystic ovary syndrome. J Fertil Steril. 2002 May;77(5):936-44. doi: 10.1016/s0015-0282(02)02955-2. PMID: 12009347. https://pubmed.ncbi.nlm.nih.gov/12009347/ 
5. Your patient’s brain may be undermining their weight-loss efforts1. Contrave. Accessed August 6, 2023. https://contravehcp.com/how-contrave-works/  
6. Zhou G, Myers R, Li Y, Chen Y, Shen X, Fenyk-Melody J, Wu M, Ventre J, Doebber T, Fujii N, Musi N, Hirshman MF, Goodyear LJ, Moller DE. Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest. 2001 Oct;108(8):1167-74. doi: 10.1172/JCI13505. PMID: 11602624; PMCID: PMC209533. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC209533/#:~:text=Metformin%20activates%20muscle%20AMPK%20and%20promotes%20glucose%20uptake.&text=Incubation%20of%20isolated%20muscles%20with,subunits%20of%20AMPK%20 
7. Kitabjian A. Metformin and PCOS: Improving Menstrual Cycle and Hormone Profiles. February 21, 2018. Accessed August 4, 2023. https://www.endocrinologyadvisor.com/home/topics/androgen-and-reproductive-disorders/metformin-and-pcos-improving-menstrual-cycle-and-hormone-profiles/ 
8. Harborne L, Fleming R, Lyall H, Sattar N, Norman J. Metformin or antiandrogen in the treatment of hirsutism in polycystic ovary syndrome. J Clin Endocrinol Metab. 2003 Sep;88(9):4116-23. doi: 10.1210/jc.2003-030424. PMID: 12970273. https://pubmed.ncbi.nlm.nih.gov/12970273/#:~:text=The%20results%20show%20that%20metformin,the%20standard%20treatment%20(Dianette) 
9. Laure Morin-Papunen and others, Metformin Improves Pregnancy and Live-Birth Rates in Women with Polycystic Ovary Syndrome (PCOS): A Multicenter, Double-Blind, Placebo-Controlled Randomized Trial, The Journal of Clinical Endocrinology & Metabolism, Volume 97, Issue 5, 1 May 2012, Pages 1492–1500, https://doi.org/10.1210/jc.2011-3061 https://academic.oup.com/jcem/article/97/5/1492/2536356  
10. Jensterle Sever M, Kocjan T, Pfeifer M, Kravos NA, Janez A. Short-term combined treatment with liraglutide and metformin leads to significant weight loss in obese women with polycystic ovary syndrome and previous poor response to metformin. Eur J Endocrinol. 2014 Feb 7;170(3):451-9. doi: 10.1530/EJE-13-0797. PMID: 24362411; PMCID: PMC3922503. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3922503/ 
11. Briden L. Cyclic Progesterone Therapy for PCOS. Lara Briden – The Period Revolutionary. December 26, 2022. Accessed August 3, 2023. https://www.larabriden.com/cyclic-progesterone-therapy-for-pcos/  
12. Özdemir O, Kurdoglu Z, Yıldız S, Özdemir PG, Yilmaz E. The relationship between atypical depression and insülin resistance in patients with polycystic ovary syndrome and major depression. J Psychiatry Res. 2017 Dec;258:171-176. doi: 10.1016/j.psychres.2016.11.043. Epub 2016 Dec 3. PMID: 28168992. https://pubmed.ncbi.nlm.nih.gov/28168992/ 
13. Mobeen H, Afzal N, Kashif M. Polycystic Ovary Syndrome May Be an Autoimmune Disorder. J Scientifica (Cairo). 2016;2016:4071735. doi: 10.1155/2016/4071735. Epub 2016 May 5. PMID: 27274883; PMCID: PMC4871972. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4871972/ 
14. Bhasin G, Wang ET, Alexander CJ, et al. Women with polycystic ovary syndrome (PCOS) have lower basal metabolic rates compared to eumenorrheic controls. J Fertility and Sterility. 2013 Sept; 100(3):S38-S39.  https://doi.org/10.1016/j.fertnstert.2013.07.1793 https://www.fertstert.org/article/S0015-0282(13)02572-7/fulltext#:~:text=Patients%20with%20PCOS%20have%20lower,associated%20with%20resting%20metabolic%20rates 
15. Georgopoulos NA, Saltamavros AD, Vervita V, Karkoulias K, Adonakis G, Decavalas G, Kourounis G, Markou KB, Kyriazopoulou V. Basal metabolic rate is decreased in women with polycystic ovary syndrome and biochemical hyperandrogenemia and is associated with insulin resistance. J Fertil Steril. 2009 Jul;92(1):250-5. doi: 10.1016/j.fertnstert.2008.04.067. Epub 2008 Aug 3. PMID: 18678372. https://pubmed.ncbi.nlm.nih.gov/18678372/ 
16. Bikman B. Chapter 15: Eat Smart: The Evidence on The Food We Eat. In Schulz C, Fraleigh J, O’Brien K, Zarkos A, eds. Why We Get Sick: The Hidden Epidemic at the Root of Most Chronic Disease–and How to Fight It. BenBella; 2020:162-163 
17. Vyakaranam S, Vanaparthy S, Nori S, Palarapu S, Bhongir AV. Study of Insulin Resistance in Subclinical Hypothyroidism. Int J Health Sci Res. 2014 Sep;4(9):147-153. PMID: 25580384; PMCID: PMC4286301. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4286301/#:~:text=Thyroid%20hormones%20T3%20and%20T4,can%20lead%20to%20insulin%20resistance  
18. Shoman M, Lee D. How Thyroid Function Affects Menstruation: Menstrual irregularities are more common in severe thyroid disease. VeryWell Health. Updated on June 21, 2022. Accessed August 22, 2023. https://www.verywellhealth.com/menstrual-problems-and-thyroid-disease-3231765#:~:text=Thyroid%20conditions%20can%20have%20an,also%20affect%20fertility%20and%20pregnancy