How the diabetic drug Metformin can be used to treat PCOS

Polycystic ovary syndrome (PCOS), also known as polycystic ovarian syndrome, is a hormonal disorder that affects an estimated 5-6 million women in the United States. The symptoms of PCOS vary person-to-person, which can make it challenging to identify. Many women suffer in silence, living undiagnosed for years. 

Non-profit organizations throughout the U.S. work to spread awareness about symptoms and information about available treatment options—from birth control to metformin. But it remains “one of the most critical, underserved, under-diagnosed and under-funded conditions affecting women’s health,” says Sasha Ottey, executive director of the non-profit PCOS Challenge Inc. 

Why do some women get PCOS, and how does it affect them?

Felice Gersh, MD, an award-winning OB-GYN, says PCOS is “the most common endocrine disorder of reproductive aged women—but it involves every aspect of a woman’s body. It affects all metabolic functions as well as all aspects of the menstrual cycle and fertility.” Common symptoms and diagnostic criteria may include: no period, an irregular period, or a heavy period; pelvic pain; extra hair growth on your face, known as “hirsutism”; acne; excess weight gain or challenges with losing body weight; and patches of dark thick skin. According to EndrocrineWeb, women with PCOS may have 25 or more cysts, or fluid-filled follicles, on a single ovary. Follicles typically burst during ovulation when they release an egg. But with PCOS, this often does not happen–each small follicle fills up with fluid, creating a cyst insead. People with PCOS may not have regular periods and may experience poor success rates at getting pregnant.  

There are a variety of reasons why young women of reproductive age might develop PCOS, but research shows that genetics, insulin resistance, glucose intolerance, and androgen excess (also known as male hormones) all can put you at risk. 

PCOS impacts women from a diverse range of backgrounds. “Women of all races and ethnicities are at risk of PCOS,” says Kate Killoran, MD, OB-GYN in Maine. But obese women and women with a family history are at increased risk of developing the disorder.” 

According to the American Cancer Society, PCOS puts women at higher risk of endometrial cancer. A 2016 literature review found that multiple studies reported a link between PCOS and endometrial cancer, but the authors did not take BMI into account, and a high BMI is an established risk factor for endometrial cancer. A recent systematic review found no correlation between PCOS and endometrial cancer in women of European or Asian ancestry. The bottom line? Definitive evidence is lacking.

What are PCOS treatments?

While there is no cure for PCOS, there are ways to manage symptoms and long-term health outcomes. Each patient’s treatment plan will be a little different, based on their specific set of symptoms. 

Dr. Killoran says that there are a few medications that may be prescribed for PCOS patients, depending on how the condition affects them. This is not a complete list, but it includes:

• Birth control pills may help control menstrual abnormalities. 
• Oral contraceptives that contain estrogen can help improve acne. 
• Metformin or other medicines for insulin sensitivity might help with metabolic abnormalities and even improve fertility. 
• Letrozole can induce ovulation when women with PCOS are trying to conceive.
• Clomiphene can be used to induce ovulation and increase the odds of pregnancy in anovulatory women with PCOS.

“Lifestyle modification, specifically exercise and calorie-restricted diet changes can improve or reverse PCOS,” Dr. Killoran adds.

Should I take metformin for PCOS?

The insulin-reducing drug metformin is sometimes used off-label as a treatment of PCOS. Early clinical trials of the drug showed evidence that metformin contributed to weight loss, reduced levels of androgens such as free testosterone, promoted regular menstrual cycles, and induced ovulation, so it may be prescribed by healthcare providers for these issues. 

Though metformin is no longer recommended as a first-line treatment for PCOS, it may be used as an alternative treatment for hirsutism, a condition related to PCOS that results in excessive hair growth near the chin, upper lip, chest, back and stomach, when first-line treatments such as oral contraceptives, clomiphene and letrozole are contraindicated.

In a meta-analysis of non-obese women with a body mass index (BMI) up to 32, the clinical pregnancy rate was similar among women taking metformin (36.7%) and women taking clomiphene (35.7%) as were live birth rates (30.3% and 30.3%) respectively. Metformin may be prescribed to women with anovulatory infertility and polycystic ovary syndrome to increase the odds of conception. Women with PCOS who conceive have a high prevalence of gestational diabetes.

What does metformin do for PCOS?

Metformin is a common medication used to treat PCOS symptoms. It was originally developed and typically is prescribed to treat Type 2 diabetes, a metabolic syndrome similar to PCOS, says Dr. Laurence Gerlis, a general practitioner in London, England.

According to research, for patients with diabetes mellitus, a disorder characterized by high blood sugar levels, metformin helps to restore the body’s response to insulin, increasing glucose tolerance and making you less insulin resistant. The role of metformin in the body is to control blood sugar by “helping the body respond better to the insulin it makes naturally, decreasing the amount of sugar the liver makes [by increasing insulin receptor activation], and decreasing the amount of sugar the intestines absorb from food,” according to the Food and Drug Administration (FDA). 

Dr. Gerlis says metformin for PCOS, when taken regularly, will lower blood glucose levels by balancing insulin levels and decreasing other metabolic effects of the condition.

Are there side effects of taking metformin for PCOS?

There are very few safety issues related to regular use of metformin, other than the loosening of bowels, Dr. Gerlis says. Gas, diarrhea, and stomach pain are some common side effects of metformin.

Dr. Gersh, on the other hand, does not prescribe metformin to her patients because it has been classified as an endocrine disruptor by some environmental scientists. Although there is much controversy surrounding them, endocrine disruptors have been suspected to be associated with altered reproductive function, breast cancer, irregular growth patterns, and more.

How much metformin should I take for PCOS? How long should metformin be taken for PCOS?

There is no consensus on a standard dose or duration of metformin for PCOS; the median dose is 1,500mg daily. Physicians often start patients on 500 mg daily, and increase the dose gradually to reduce side effects of metformin.

Metformin is available through prescription only, and was approved by the Food and Drug Administration (FDA) in 1994 in the United States. Metformin is taken orally, and is available under the brands Fortamet, Glucophage, Glumetza, and Riomet.

“Since metformin is well-established with a good safety profile, it is highly recommended to start it early in the management of PCOS,” Dr. Gerlis advises. 

Long-term use of metformin is considered relatively safe, but in rare cases, lactic acidosis (lactic acid buildup in the bloodstream) may occur. If you stop taking metformin for PCOS, you are likely to experience an increase in symptoms such as irregular menstrual cycles, increased androgen levels, and weight gain. 

How does metformin help PCOS and weight loss? How does metformin help with infertility?

For weight loss and infertility, the efficacy of metformin is not as clear cut.

Dr. Killoran says that patients with PCOS who may want to try metformin therapy to manage their symptoms are typically overweight or obese and trying to conceive, or are trying to prevent metabolic syndrome, cardiovascular disease, or worsening diabetes mellitus. 

While metformin use is associated with weight loss, the results are inconsistent, she says. In one recent longitudinal study, metformin users lost an average of 3.7% of their body weight within the first year, maintaining the weight loss after 4 years. 

Another 6-month randomized, placebo-controlled trial of overweight women found that after 6 months, there was no significant difference in weight reduction among a group of individuals taking metformin and a control group who took a placebo and made lifestyle modifications–eating a 500-1000 calorie deficit each day combined with 150 minutes of physical activity each week. People in the metformin group plus lifestyle intervention  experienced the most significant reduction in weight. 

Are there natural alternatives to metformin for PCOS?

The most commonly recommended natural treatments for PCOS are finding ways to be more active, and eating more whole foods. Dr. Gersh believes that the number one way to address PCOS is through lifestyle changes, including:  

• Eating a plant-based, balanced diet
• Reducing stress
• Focusing on sleep
• Incorporating physical exercise.

These new habits can have a positive effect on symptoms. For her patients, Dr. Gersh recommends a variety of vitamin supplements, in conjunction with dietary changes and exercise to treat symptoms of PCOS. For example, vitamin B12 may be recommended to be taken with or after metformin treatment, as malabsorption of vitamin B12 could be an effect of metformin if it’s used long-term.

Meanwhile, Dr. Killoran says that PCOS impacts each person differently. She says it’s important to treat PCOS even if the patient’s symptoms aren’t bothersome, yet. “All should be aware of their risk for later medical problems such as metabolic syndrome and cardiovascular disease,” she advises. “The decision to treat PCOS and with what should be based on what a woman’s symptoms are but also to reduce risk.”

If you are considering metformin, schedule a follow-up with your healthcare provider  to see what is right for you.