OCPs Made Simple: Mechanism, Dosing Regimens, and the Difference Between Monophasic & Multiphasic Formulations
Welcome back to the OB/GYN Resident Survival Guide. In this episode, we’re breaking down the combined oral contraceptive pill (COC)—how it works, how it’s prescribed, and what actually matters when choosing between different formulations.
Before I jump in, if you are a 4th year medical student planning to start your OBG/YN residency this July, I put together an OB/GYN Residency Starter Pack with tips and resources to help you get ready for July 1st. It’s free and doesn’t take very long to go through so if you’re interested, go check out the link!
Since their introduction in the 1960s, oral contraceptive pills have become the most commonly prescribed form of contraception in the United States and one of the most widely used reversible methods worldwide. While there are both combined hormonal pills and progestin-only pills, this episode focuses specifically on combined oral contraceptives.
Let’s start with the physiology.
A Quick Review of the Menstrual Cycle
Under normal circumstances, ovarian follicles synthesize and release estradiol, which peaks just before ovulation. After ovulation, the remaining follicle becomes the corpus luteum and begins secreting progesterone.
Toward the end of the luteal phase (and beginning of the follicular phase), estradiol and progesterone levels fall. The hypothalamus senses this change and releases pulsatile gonadotropin-releasing hormone (GnRH), which stimulates the anterior pituitary to release follicle-stimulating hormone (FSH) and luteinizing hormone (LH). This process recruits follicles and ultimately leads to ovulation.
This hypothalamic–pituitary–ovarian axis is exactly where combined oral contraceptives exert their effects.
How Combined Oral Contraceptives Work
Combined oral contraceptives contain synthetic estrogen and progestin. They prevent pregnancy through several complementary mechanisms:
Suppression of GnRH release at the hypothalamic level
Estrogen-mediated suppression of FSH, blocking follicular development
Progestin-mediated suppression of LH, preventing the LH surge and ovulation
Thickening of cervical mucus, making sperm penetration more difficult
Thinning of the endometrial lining, reducing implantation potential
Impairment of tubal motility
Together, these effects reliably inhibit ovulation and reduce the likelihood of fertilization and implantation.
Common Synthetic Hormones in COCs
The most frequently used synthetic estrogen is ethinyl estradiol, though estradiol valerate and mestranol are also found in some formulations.
Synthetic progesterones—referred to as progestins—include agents such as norethindrone, norethindrone acetate, levonorgestrel, desogestrel, drospirenone, and norgestimate, among others.
While there are many formulations available, their contraceptive efficacy is comparable when used correctly.
Cyclic vs. Continuous Dosing
Combined oral contraceptives can be prescribed using either cyclic or continuous regimens.
Cyclic Regimens
Cyclic packs typically contain 21–24 hormone pills followed by 4–7 placebo pills. During the placebo week, hormone withdrawal triggers bleeding that patients perceive as a period.
Historically, this schedule was designed to reduce estrogen exposure and to provide reassurance through monthly bleeding. However, modern pills contain much lower estrogen doses, and current evidence shows that continuous daily hormone use is just as safe as cyclic regimens.
Continuous Regimens
Continuous dosing involves taking active hormone pills every day with no placebo interval. This suppresses withdrawal bleeding entirely.
Importantly, the hormone-free interval in cyclic regimens can allow follicles to develop and estradiol levels to rise, which may contribute to withdrawal symptoms such as pelvic pain or mood changes. Continuous dosing avoids this fluctuation.
One advantage of cyclic regimens is that they may result in less unscheduled breakthrough bleeding, as intermittent follicular estradiol production can help stabilize the endometrium.
Monophasic vs. Multiphasic Pills
Another distinction among COCs is whether they are monophasic or multiphasic.
Monophasic Pills
These contain the same dose of estrogen and progestin in every active pill throughout the cycle.
Multiphasic Pills
These vary the dose of one or both hormones across the pill pack in an attempt to mimic natural hormonal fluctuations. This includes biphasic and triphasic formulations.
Multiphasic pills were originally developed to minimize hormone exposure and reduce side effects. However, current evidence does not demonstrate meaningful clinical advantages over monophasic pills. Triphasic pills may be associated with slightly less breakthrough bleeding, but biphasic pills are less commonly used due to higher rates of unscheduled bleeding.
Overall, monophasic pills remain a reliable and commonly preferred option in clinical practice.
Key Takeaways
Ovarian follicles produce estradiol, and following ovulation the corpus luteum secretes progesterone. When hormone levels fall, GnRH release stimulates FSH and LH production, leading to follicular development and ovulation.
Combined oral contraceptives interrupt this process by suppressing GnRH, FSH, and LH, while also thickening cervical mucus, thinning the endometrium, and reducing tubal motility.
COCs can be prescribed in cyclic or continuous regimens. Cyclic dosing includes a placebo interval that produces withdrawal bleeding, while continuous dosing eliminates hormone-free days and suppresses bleeding altogether.
Monophasic pills provide consistent hormone dosing throughout the cycle, whereas multiphasic pills vary hormone levels. Despite theoretical benefits, multiphasic formulations have not been shown to be superior overall.
As always, references and additional resources are available down below, along with the free OB/GYN Residency Starter Pack for incoming interns.
Thanks for reading, and I’ll see you in the next episode!
References
United Nations Contraceptive Use by Method 2019
StatPearls Oral Contraceptive Pills
History of oral contraceptive drugs and their use worldwide
UpToDate: Combined estrogen-progestin oral contraceptives: Patient selection, counseling, and use
Rationale for eliminating the hormone-free interval in modern oral contraceptives
Triphasic versus monophasic oral contraceptives for contraception
Biphasic versus triphasic oral contraceptives for contraception
Biphasic versus monophasic oral contraceptives for contraception
UpToDate: Normal menstrual cycle
Hoffman, Barbara L.; Schorge, John O.; Bradshaw, Karen D.; Halvorson, Lisa M.; Schaffer, Joseph I.; Corton, Marlene M.. Williams Gynecology, Fourth Edition (p. 121). (Function). Kindle Edition.
