How does The Pill work?

To answer this question, it’s helpful to recap the role of hormones in a woman’s menstrual cycle. That’s actually a pretty big topic so we’ll just look at what causes ovulation and that is a surge of Luteinizing Hormone (LH). “Ovulation” is the release of a single egg from the follicle (or sac) in which it had been residing. Occasionally, two eggs will be released – one from the left ovary and the other from the right which, if both fertilized, results in fraternal twins. Amazingly enough, the leftover sac in the ovary (called the “corpus luteum”) has an effect on thickening the uterine lining and preparing the woman for pregnancy – pretty amazing, eh? Even our biological rubbish has a purpose. Getting pregnant requires an egg; hence a class of contraceptives (including The Pill) focuses on preventing ovulation.

The general approach is to prevent the LH surge and hence the release of an egg. The LH surge is triggered by super elevated levels of estradiol (which is a type of estrogen). When a follicle becomes very mature, it releases these super elevated levels of estradiol. Therefore, by preventing follicular maturation, we can keep estradiol levels down, and hence the LH surge will not be triggered.  In order to inhibit follicular development, one decreases the levels of Follicle Stimulating Hormone (FSH) that are released by the pituitary gland. Increasing the levels of progestin in a woman’s system inhibits the release of both FSH and LH. It’s also the case that elevated levels of estrogen inhibit the release of FSH – and so “combined contraceptive pills” contain both Progestin (used to inhibit release of FSH and hence follicular development) and Estrogen (specifically ethinyl estradiol), which also inhibits release of FSH.

Hence, to recap, the way that The Pill works is as follows:

  • Add progestin to woman’s system. Increased levels of progestin result in decreased levels of FSH and LH (b/c progestin decreases the frequency of release of GnRH from the hypothalmus).
  • Add small amounts of estrogen to the woman’s system. Slightly elevated estrogen levels also inhibit the release of FSH.
  • Since FSH causes follicles to mature, a decreased level of FSH results in halting follicular development, which in turn results in lower levels of estradiol.
  • Without elevated levels of estradiol AND with immature follicles, the LH surge does not happen. If the LH surge doesn’t happen then neither does ovulation.

Maybe you will have this question – I did: We know that the Pill contains some estradiol (estrogen) and that’s “a good thing” because it causes less FSH to be released. But we also know that if there is a lot of estradiol (estrogen) in the woman’s system (as occurs at the end of the follicular development phase) then this causes an LH surge. So how to resolve this apparent contradiction – wherein a woman ingests some estradiol as part of taking the Pill but evidently this does not result in triggering the LH surge?

Here’s the answer:

  • [The Negative Estradiol Feedback Loop] The threshold of estrogen required to trigger the “negative feedback” mechanism (wherein levels of FSH and LH drop) is very low. That is, by adding a little bit of estrogen, we can cause this effect.
    • Note that this is part of what causes a single follicle to mature each cycle. Once that follicle starts developing, it starts releasing estradiol, which inhibits FSH, which inhibits the growth of other follicles.
      • “Serum estradiol levels begin to rise as a result of the emergence of the dominant follicle. The rising estradiol, through the negative feedback loop, suppresses FSH levels (see Fig. 1) to concentrations that are too low to sustain maturation of the other follicles in the cohort…” Source:
  • [The Positive Estradiol Feedback Loop] However, at a much higher threshold, the effect becomes the opposite. Namely, when estradiol levels get really elevated (as is the case at the end of the follicular phase where we have a single big follicle which is producing a bunch of estradiol), we see that this induces the LH surge.
    • This is the positive estradiol feedback loop.
  • Note that it may be the case that the positive estradiol feedback loop acts on “different neuronal cell populations [receptors] than those modulating the estradiol negative feedback loop.”
  • Therefore, the effect of elevated levels of estradiol depends on how elevated the level is.
    • This is because the level of estradiol produced by a mature follicle at the end of the follicular phase is MUCH HIGHER than the amount of estradiol required to trigger the initial negative feedback effect.
    • Therefore, the amount of estradiol in the Pill is enough to trigger the negative feedback loop but not enough to trigger the positive one.
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2 Responses to How does The Pill work?

  1. Marie says:

    Would taking two of the last .01 EE pills in an oc like azurette 12 hours instead of 24 hours apart throw things off too much and induce ovulation?

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