Evidence Based
Polycystic ovarian syndrome impacts millions of women. The number of cases has increased over the last decade,[1] and it is estimated as many as one in five women of reproductive age are affected. Symptoms are related to hormonal imbalance, which contributes to weight gain, changes in hair growth, and the potential for infertility.
Common concerns among women with polycystic ovary syndrome, i.e., PCOS, are weight management and controlling the risks of developing diabetes mellitus. Metformin treatment has become a common option for both. When managing PCOS, these are the concerns addressed by metformin:
- Weight Loss.
- PCOS-related insulin resistance.
- A decrease in androgens.
So, what dosage of metformin is needed to help promote weight loss in individuals managing PCOS? We will discuss dosing specifically while also considering some of the overall risks and benefits of therapy to help ensure the medication is used safely and effectively.
Does Metformin Cause Weight Loss For Individuals Managing PCOS?
Yes, studies have suggested metformin is associated with weight loss. Specifically in overweight or obese individuals who are managing polycystic ovarian syndrome, metformin has been associated with an average weight loss of about 5% of baseline body weight[2] after a period of six months.
This amount of weight loss is enough to predict potential beneficial effects:
- Lower risk of cardiovascular disease.
- Lower risk of diabetes.
- Improved quality of life measures.
Metformin For Weight Loss In PCOS: How It Works?
To better understand how metformin can be helpful, it is useful to consider the changes occurring in your body that are associated with PCOS.
What Is PCOS?
While there is no well-established cause of PCOS, it does appear that genetics[3] may play a role. A primary risk factor is having a mother or sister with PCOS, but other factors have been associated as well. For instance, obese patients are also at a higher risk, potentially independent of familial history.
A grouping of symptoms defines PCOS:
- Cysts in one or both ovaries.
- Hormonal imbalance characterized by high levels of androgens, e.g., testosterone, or signs of imbalance, like increased facial hair.
- Ovulation interference, which can lead to irregular or absent menstrual cycles and infertility.
Not all individuals experience all three – PCOS can be diagnosed without the presence of cysts on the ovaries, for instance. The cysts that are seen are actually follicles in the ovary that have stopped developing[3] and which have accumulated fluid. Once such a follicle enlarges to larger than two centimeters, it is termed a cyst. Such follicle abnormalities have implications for fertility, as ovulation can be affected.
PCOS is associated with metabolic imbalances, which can raise the risk of heart disease and cause insulin resistance, leading to elevated glucose levels and higher rates of diabetes. Weight gain is also common, and losing weight can be particularly difficult around the waist.
How Does Metformin Help With Managing PCOS?
Metformin is a prescription medication traditionally used for the management of diabetes. It does not increase insulin secretion but does help to reduce insulin resistance. Your tissues are more sensitive to the insulin produced. Insulin is responsible for transporting glucose from the bloodstream into cells, which helps maintain blood sugar and metabolic balance. In essence, metformin helps your body’s natural insulin do its job more effectively.
Metformin therapy has been utilized in PCOS patients for about 30 years,[4] and a variety of studies have been conducted related to its potential benefits. So, what does this research indicate?
Benefits Of Taking Metformin For Weight Loss In PCOS
It should be noted that the potential benefits of taking metformin for PCOS may extend beyond weight loss, but body weight regulation is undoubtedly part of the picture. The overall benefits seen in overweight women using metformin for PCOS are reductions in:[4]
- Body mass index, or BMI.
- Waist circumference, which is an improved predictor of cardiovascular risk compared with BMI.
- Low-density lipoprotein, or LDL cholesterol, i.e., the bad cholesterol.
- Testosterone levels.
- Systolic blood pressure, or SBP.[5]
While many individuals are interested in losing weight quickly, it is important to note that a healthy rate of weight loss is typically defined as one to two pounds per week. Taking steps to try to lose weight more quickly, such as heavily restricting your diet, can lead to potential nutrient deficiencies over time. Your doctor or nutritionist can help you develop a plan that maintains a healthy balance.
Reductions in weight, waist circumference, abnormal lipids, and BMI are all beneficial for reducing the risk of cardiovascular disease. Individuals with polycystic ovary syndrome respond well to metformin’s effects on testosterone[4] levels. They also can see reduced levels of unwanted hair or acne. Metformin has also been associated with improved regularity of menstrual cycles[6] among women with PCOS.
Weight Loss
In general, clinically significant weight loss is 5% or more of baseline body weight. In some studies, metformin has helped some individuals achieve this.[2] Baseline body weight would be defined as your weight before starting metformin. It is used to compare with your weight after using metformin for a period of time. Clinically significant weight loss is associated with:[7]
- Improved overall quality of life.
- Lower risks of cardiovascular disease.
- Lower risks of diabetes.
- Reduced knee pain.
- Improved mobility.
- Lower risk of developing sleep apnea.
Of all therapies for weight loss, metformin is among the most appropriate options for many overweight individuals managing PCOS. Many weight loss supplements and medications may not be appropriate because of stimulant content. Assessing the impact of stimulants on cardiovascular risk is essential. It is always best to consult your doctor before starting new therapy to ensure products will be safe and effective for you as an individual.
Lifestyle modifications help lose weight and are recommended regardless of whether metformin is considered for individuals managing PCOS. It can be beneficial to increase physical activity and focus on improvements in diet. Cardio exercises that increase your heart rate can be efficient. Tracking carbohydrates and overall calorie intake, along with maintaining hydration, can help.
Blood Glucose
Interestingly, metformin has achieved mixed results for fasting blood glucose levels among overweight patients with PCOS. It would be important to note that many studies are not evaluating women with both PCOS and diabetes specifically. The studies focusing on diabetes management in the context of PCOS return favorable results.[8] It would certainly be logical to include metformin as a part of a diabetes prevention program.
Using Metformin During Pregnancy
In the context of pregnancy, it should be noted that metformin has not been associated with benefits for:[9]
- High blood pressure – or preeclampsia.
- High birth weight.
- Gestational diabetes.
However, metformin may help some individuals at risk for preterm delivery, so using metformin may be appropriate for this purpose. Metformin exposure in the womb has been associated with higher weight during childhood. It is still unclear whether the medication is the direct cause. The gastrointestinal side effects of metformin align somewhat with morning sickness. Yet, overall rates of nausea and vomiting have not been worse among pregnant individuals using metformin.
Metformin Dosage For PCOS Weight Loss
Standard metformin dosage follows a fairly set pattern whether it is being used for blood sugar management or PCOS. The dose is typically titrated or slowly increased over a period of weeks to allow the body to adjust. This reduces the chances of experiencing gastrointestinal side effects.
Schedules can vary, but a fairly typical approach may look like this:
- 500 milligrams once daily with supper for one week.
- 500 mg twice daily for one week.
- 500 mg with breakfast and 1,000 mg with supper for one week.
- 1,000 mg twice daily ongoing.
Targeting a total of 2,000 mg for ongoing use is a fairly standard approach, but there is some potential for variability in the total dosage as well. For instance, in a study evaluating weight loss in PCOS patients[2] specifically, participants used the following target doses based on initial BMI:
- 1,500 mg total for patients with a BMI <30 kg/m2.
- 2,000 mg total for patients with a BMI between 30 and 35 kg/m2.
- 2,500 mg total for patients with a BMI >35 kg/m2.
In this particular study, only the obese subgroup received a target dose of higher than 2,000 mg. The overall average weight loss was about 5.6% of initial body weight, which is considered clinically significant. The weight loss results for individuals using metformin for support with PCOS were observed over time. While some saw potential results within two months, overall results were observed in a 6-month period.
It should be noted that some individuals have a difficult time tolerating the potential gastrointestinal side effects of metformin. They may decide to stay on lower doses of the medication. Working with your doctor will help you determine which metformin dose is most appropriate for you and your specific needs.
Metformin Side Effects
Overall, metformin is considered a safe medication but does have some precautions. The most common side effects are gastrointestinal and include:
- Nausea and vomiting.
- Stomach discomfort.
- Diarrhea.
These side effects can be made less likely by taking an extended-release tablet or by taking the medication with meals. Slowly tapering the medication will also give your body a chance to adjust, which can also make these effects less likely.
Lactic Acidosis
A potentially serious side effect associated with metformin is lactic acidosis.[10] This is a metabolic imbalance caused by changes in blood glucose levels. They can be severe enough to require hospitalization or can be fatal in some cases. The risk of developing lactic acidosis is higher for individuals with:
- Reduced kidney function.
- Reduced liver function.
- A history of alcohol abuse.
- Age 65 or older.
- The use of other active glucose-modifying medications.
Your doctor should discuss your past medical history and monitor labs before starting and during metformin therapy to ensure your safety.
Vitamin B-12 Monitoring
Metformin has been associated with decreased B12 levels.[11] Low B12 levels can cause anemia, which can make you tire quickly or make it difficult to catch your breath. If you have a history of B12 deficiency, it is essential to discuss this with your doctor in the context of metformin therapy.
Lower levels of B12 have also been linked to neuropathy,[12] e.g., nerve pain. For this reason, metformin could be considered an indirect contributor to new or worsening nerve pain. Diabetes itself can also cause neuropathy, so there is the potential for confusion regarding the source of worsening nerve pain. If you have diabetes, take metformin, and are experiencing nerve pain, it can be helpful to ensure your B12 levels are being monitored.
Conclusion
While metformin can help support weight loss efforts, it has also been associated with several other potentially beneficial effects for the management of PCOS. It is helpful to be aware of the precautions associated with therapy – ensuring your doctor has an accurate view of your medical history is crucial for safe use. Managing PCOS can be very frustrating, but support is available to help you on your journey!
Frequently Asked Questions
There is some evidence that metformin use in individuals managing PCOS may result in an average weight loss of about 5% of baseline body weight. These individuals were explicitly overweight or obese and were evaluated after six months of use.
It depends on your therapy goals. Hormone regulation can take a month or two before effects are appreciated. Healthy rates of weight loss are about one to two pounds per week, and meaningful results occur over a few months.
While the withdrawal of metformin does not necessarily cause a rebound effect, it is possible to regain weight if the underlying mechanisms of PCOS are not being addressed by other means.
Metformin was previously a first-line therapy option for the management of type 2 diabetes. For individuals with diabetes who would benefit from weight loss, newer medications like GLP-1 agonists are being considered. Metformin remains a viable option for some patients.
It depends on your goals of therapy. Monitoring your weight, waist circumference, A1C, or other signs and symptoms like acne can help you determine how well the medication is working for your needs.
