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The OB/GYN Resident Survival Guide
#18: OCPs Made Simple: Mechanism, Dosing Regimens, and the Difference Between Monophasic & Multiphasic Formulations
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Welcome back for another episode of the OB GYN Resident Survival Guide, a podcast with bite sized clinical pearls that you can consume on the run. I AM your host, Dr. Casey Miller, and today we're going to be covering the birth control pill, specifically the combined hormonal pill. As a reminder, if you're a 4th year medical student about to start your OB GYN residency this July, I put together an OB GYN residency starter package with some tips and resources to help you get ready for July 1st. The link to that is in the show notes and it's free, so go check it out. All right, let's get into the meat of this episode. Since their development and release in the 1960s, oral contraceptive pills, or OCPs, have become the most commonly prescribed method of contraception in the United States and one of the most commonly used reversible types of contraception in the world. There are combined hormonal pills, which contain a synthetic form of estrogen and progesterone, as well as progestin only pills. Today I'm going to be focusing on the combined oral contraceptive pill and from here on out, I will refer to that as a CoC. So as a reminder, ovarian follicles synthesize and release estradiol, which peaks just before ovulation. After ovulation is complete, what's left of the follicle turns into the corpus luteum, which then releases large amounts of progesterone until it degenerates and the process starts all over again. The very end of the luteal phase slash. Beginning of the follicular phase is when estradiol and progesterone are at their lowest. The hypothalamus senses that something is missing and so it sends a pulse of gonadotropin releasing hormone to the pituitary. This then stimulates the release of follicle stimulating hormone and luteinizing hormone to begin recruiting follicles, which then leads to ovulation and you know the rest. From here on out, I'm going to use the abbreviations. So gonadotropin releasing hormone will be GnRH, follicle stimulating hormone will be FSH, and luteinizing hormone will be LH. So COCs work at that level in a few ways. Firstly, they both work at the level of the hypothalamus to inhibit the release of GnRH that pulsatile GnRH estrogen also works directly at the anterior pituitary to suppress fsh, which then blocks folliculogenesis. Additionally, Progesterone also works directly at the anterior pituitary to suppress the release of lh, thus inhibiting the LH surge and subsequent ovulation. Lastly, the progestin component also thins out the endometrium, thickens in cervical mucus and impairs tubal motility. I do want to briefly touch on the different names for synthetic estrogens and progesterones because there are so many of them. Probably the most common form of synthetic estrogen you'll see is ethinyl estradiol, but others include estradiol, valerate and mestrenal. Synthetic progesterones are referred to as progestins and include NORA syndrome, norethindrone acetate, levonorgestrel desogestrel, drospurinone and nordestamate, to name just a few. So now that we've briefly reviewed the menstrual cycle and how COCs actually work, let's quickly talk about the two dosing regimens. Cyclic or continuous? Cyclic COCs have a pack of 21 to 24 hormone containing pills and four to seven placebo pills. So when the hormone pill is stopped, this stimulates a withdrawal bleed that the patient perceives as a period. Continuous COCs have a pack of 28 hormone containing pills, meaning there are no off days and the perceived menstruation is suppressed. When the birth control pill was first developed, much higher doses of estrogen were used and it was assumed that minimizing the exposure to estrogen with a seven day off period would be safer. Additionally, in order for the pill to be accepted culturally, it was more appealing for women to be able to still have a monthly bleed in order to reassure them that they were not pregnant based off of current evidence. With the much lower doses of estrogen utilized in the modern pill, taking a daily hormone pill continuously is just as safe as having a seven day break. In fact, taking four to seven days off is actually more likely to precipitate withdrawal symptoms like pelvic pain and mood swings. And this is because even with just a few days off, it is possible for follicles to evolve and release estradiol during that time. The upside of that or of a cyclic regimen is that patients might be less likely to have random breakthrough bleeding because the ovarian follicles can secrete a little bit of estradiol which can help to repair and proliferate that endometrial lining, so it's not as fragile. So where does the whole monophasic and multiphasic thing come in Monophasic just means that the dose of estrogen and progestin is the same in every hormonal pill every day throughout the cycle. Multiphasic pills, like the biphasic and triphasic pills, attempts to mimic the natural hormone fluctuations that occur throughout a natural cycle. So the dose of one or both hormones will vary throughout the cycle or throughout the pack of pills. And these variations were developed mainly to reduce hormone exposure to patients and potential side effects, which really, from a marketing standpoint, is something that could potentially make them more competitive as a product. At the end of the day, the evidence does not show any real clinical benefit to multiphasic pills when compared to monophasic pills. Triphasic pills may be associated with less breakthrough bleeding, but that's about it. And biphasic pills are not as common due to side effects related to increased breathing. Breakthrough bleeding. All right, let's summarize. Ovarian follicles secrete estradiol, and after ovulation, the remaining follicle turns into the corpus luteum and secretes progesterone. As these levels fall, the hypothalamus responds with a pulsatile secretion of GnRH, which then stimulates the release of FSH and LH from the anterior pituitary to stimulate follicle growth and ovulation. COCs contain a synthetic estrogen and progestin. They work by suppressing ovulation, thickening cervical mucus, thinning the endometrial lining, and minimizing tubal motility. They can be prescribed in a cyclic or continuous fashion, where cyclic regimens include a placebo week, where the patient then experiences a withdrawal bleed, and continuous regimens have no placebo week and the patient takes a hormonal pill every day and does not experience withdrawal bleeding. The difference between monophasic and multiphasic pills is the daily dose of estrogen or progestin on varying days of the cycle. Monophasic pills have the same dose of both hormones every day, whereas biphasic or triphasic pills have varying doses of one or both hormones to mimic a natural cycle. Overall, multiphasic pills have not been shown to be superior to monophasic pills, but may be associated with less breakthrough bleeding, particularly when comparing the triphasic to the biphasic constitutions. That's it for today. Per usual, all of the references are listed in the show notes, along with additional reading and links to the Residency starter pack. I will see you in the next episode. Have a great week.