INSULIN RESISTANCE & ANOVULATION:
- women with a high BMI and/or with a diagnosis PCOS will often have very high insulin, even when a HbA1C is perfectly normal.
- your ovaries are very sensitive to insulin.
- when insulin is high, it acts directly on the ovaries and causes them to increase testosterone, synthesis.
- high insulin lowers your SHBG, which is protein in your blood that binds testosterone, thus keeps your free testosterone from being active.
- the high testosterone interferes with normal folliclar maturation, and prevents the egg from rupturing, ie: prevents ovulation.
- this process causes menstrual cycles to become long, irregular, and anovulatory.
- when insulin is effectively brought down with weight loss, exercise, and medication, your ovulation should return, at least for some cycles.
- when ovulatory cycles return, a medication called "letrozole" is very effective in helping women with PCOS achieve a pregnancy.
METFORMIN VS GLP-1 AGONIST
Metformin has been around for a long time. Therefore, its safety and efficacy is well established. Typically, it is prescribed to bring down high blood glucose levels, demonstrated with a high HbA1C level. However, as mentioned, high insulin levels even in the setting of normal HbA1C, can significantly affect ovulation and make achieving a pregnancy very difficult if not impossible. Some women simply cannot tolerate metformin, since it can often cause GI side effects, such as abdominal bloating, nausea, gas, and diarrhea.
Personally, I don't recommend full dose GLP-1 agonists for weight loss because I don't think we have had enough time to demonstrate long-term safety of these drugs. However, GLP-1 agonists at lower doses have been used to treat type 2 diabetes for over 20 years. The first GLP-1 was called exenatide (Byetta) and was approved by the FDA in April 2025. Since then, many other GLP-1 agonists came on to the market.
- Tirzepatide
- Semaglutide,
- Liraglutide
For my patients who are overweight and having problems achieving a pregnancy, I would recommend you consider making an appt with either your primary care doctor or with a provider at Lavender Sly Health to be evaluated to see if a GLP-1 agonist is right for you. If your provider agrees, my recommendations would be to try a very low dose of Tirzepatide such as 2.5 mg daily and titrate up to 4-4.5 mg as needed to achieve weight loss. In my experirence, this small dose (typically used for Diabetes) is successful in helping women who are overweight lose weight when combined with a good diet and daily exercise. These life-style changes are of the utmost importance, since oftentimes, this will allow the patients to wean off the GLP-1 agonist when their weight loss is achieved without gaining the weight back.
The amazing benefit is, there appears to be lot of research being published showing that when GLP-1 agonists are taken (via an injectable) women are ovulating more! *See research articles published here.
However, since we do not have any research demonstrating GLP-1 agonists are safe in pregnancy, an 8-week washout period is recommended prior to attempting conception.
