Progestins

Today we welcome Dr. Ben Brown, who is an assistant professor in the Division of Emergency Obstetrics and Gynecology at Women and Infants Hospital and the Warren Alpert Brown School of Medicine. Dr. Brown is also completed a fellowship in Family Planning, and thus shares with us his expertise in progestin-based contraception!

We quickly reviewed initially that progesterone naturally serves as an inhibitory feedback to luteinizing hormone during the menstrual cycle. There were also a number of downstream effects of progesterone, including cervical mucus thickening, stabilizing the endometrial lining, and down-regulating both systemic progesterone and estrogen receptors — you can review all of these again with our episode on the menstrual cycle if you missed it. These mechanisms of action underlie the way progestins work clinically. We do not cover the anti-progestins (mifepristone) and selective progesterone receptor modulators (ulipristal) today.

We then reviewed the generations of progestins. As Dr. Brown states, knowing drosperinone as a 4th generation is probably a good thing, but otherwise some of this is just good to know as a “contraception nerd.” The generations are summarized below in a nice table:

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Dr. Jose Antonio Guerra Guirao

We then spoke about the delivery methods beyond the drugs — pills, injections, IUDs, implants, and more!

Side effects and contraindications are important to know for all forms of contraception. Here are a few that we review:

• Androgenicity: more apparent in combined-hormonal methods, due to upregulation of SHBG by estrogen. Some progestins (particularly 1st generation) also competitively bind androgenic receptors — even sometimes if given without estrogen, those progestins may actually produce androgenic side effects! That said, this is quite uncommon.

• Thrombosis: this can be very confusing and controversial:

  • Estrogen-containing methods will raise risk of both venous and arterial clots.

    • Drosperinone and other later-generation progestins has received poor press due to higher risk of thrombosis in combined formulations. The risk is overall still very low: 7-13 events per 10,000 woman years. But compared to pregnancy as a competing outcome, 20-30 events/10k woman years, and postpartum 40-60/10k woman-years!

  • Progestins alone can also raise arterial thrombus risk.

    • These are patients who you consider to have significant endovascular risk factors — longstanding poorly-controlled diabetes, coronary disease, heavy smoking, etc. This is because progestins can shift lipid profiles to a more androgenic appearance - lower HDL, higher LDL and total cholesterol.

  • The CDC’s US MEC guidelines are an excellent tool to cross-reference comorbidities against contraceptive methods.

• Breast cancer: current or prior is a relative contraindication to hormonal contraception.

• Severe liver disease: contraindicated due to impaired hepatic processing of steroid hormone.

• Bariatric malabsorptive procedures: may not be great candidates for progestin-only pills due to need for consistent dosing time.