The Menstrual Cycle!

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2 PHASES: FOLLICULAR & LUTEAL

The follicular phase refers to follicular maturation, lasting from the onset of menses until ovulation.

The luteal phase refers to corpus luteum maturation, and lasts from ovulation until onset of the next menses. 

The menstrual cycle is traditionally taught to last 28 days, although newer survey evidence suggests an average duration of 29.3 days. Variability in menstrual cycle duration largely results from variation in the length of the follicular phase; the luteal phase is relatively fixed at 14 days with minor variation.


FOLLICULAR PHASE & OVULATION: 

FSH promotes the growth of ovarian follicles, which secrete estradiol. Interestingly, estradiol exerts negative feedback on the pituitary until 1 day before ovulation, at which point this negative feedback suddenly switches to positive feedback, triggering the LH surge. The LH surge stimulates ovulation, or the release of the ovum from a dominant follicle.

The follicular phase is also known as the proliferative phase because of the effects of estrogen. Estrogen stimulates growth of the endometrium (both the glands and stroma) and elongation of the spinal arteries. Estrogen also up-regulates progesterone receptors in target tissues. 


LUTEAL PHASE

“Luteal” and “luteinizing” refer to the formation of the corpus luteum (Latin for “yellow body”), which functions as a temporary neuroendocrine organ in secreting estradiol and progesterone. 

Progesterone, just like estrogen in the follicular phase, exerts negative feedback on the pituitary during the luteal phase; however progesterone down-regulates estrogen receptors in some target tissues, including the endometrium, decreasing their responsiveness to estrogen. Thus endometrial proliferation slows, glands become more tortuous with increased mucosal secretions, the stroma becomes edematous, and spiral arteries become more coiled. For this reason, the luteal phase is also known as the secretory phase

If fertilization does not occur, there is no HCG to maintain the corpus luteum–it regresses (eventually becoming the corpus albicans) and estrogen/progesterone levels decline. This decline leads to loss of endometrial blood supply and eventual sloughing, or menses.


QUESTIONS! 

  • Recognizing their effects on the pituitary, how does exogenous estrogen/progestin affect ovulation?
    • Estrogen/progestin-based contraception prevents pregnancy via negative feedback on the pituitary. Estrogen and progesterone have opposing effects on the endometrium, which helps explain the unpredictable bleeding that occurs on these forms of contraception.
  • Why does continuous progestin-based contraception cause unpredictable bleeding?
    • Progestin leads to the development of a thin atrophic endometrium that may slough unpredictably. Interestingly, the levonorgestrel-releasing IUD (e.g. Mirena) causes less menstrual bleeding than other progestin-based forms of contraception (e.g. Nexplanon, minipill). Another way to think about this is that the levonorgestrel-releasing IUD is more effective at treating menorrhagia than other progestin-based therapies. But why? It’s not exactly clear, but it appears that the IUD releases a higher concentration of levonorgestrel locally to the endometrial tissue in comparison with other therapies.
  • How do anovulatory cycles affect menses? 
    • Anovulatory cycles are most common following menarche and during perimenopause. In short, anovulatory cycles result from dysfunctional feedback of estrogen on the pituitary. The absence of the LH surge leads to follicle atresia; the lack of a corpus luteum means no progesterone production. Unopposed estrogen induces endometrial proliferation without the stabilizing effect of progesterone, leading to unpredictable and sometimes heavy bleeding (i.e. dysfunctional uterine bleeding.)
    • Another important point is that menstrual irregularity is almost always the result of anovulatory cycles. But the converse is not true–monthly menstrual regularity does not necessarily indicate underlying regular ovulatory cycles. 

*Blog post based on Med-Peds Forum talk by Matt Lorenz, MP Core Faculty