The Menstrual Cycle

On today’s episode we welcome Dr. Jay Huber. Jay is a 3rd year fellow in reproductive endocrinology and infertility at the Warren Alpert Brown School of Medicine, and today he demystifies the HPO axis, the menstrual cycle, and all of the hormonal interplay.

It’s always helpful to follow along to one of the “menstrual cycle” diagrams, one of which we include here for reference:


As Dr. Huber reminds us, the ovary really runs the show due to its negative feedback effect on the hypothalamus. However, thinking top down:

  • GnRH is release from the hypothalamus in a pulsatile fashion, triggering release of FSH and/or LH, depending on the timing of the cycle.

  • In the follicular phase of the ovary, FSH stimulates development of a dominant follicle. Once the dominant follicle is large enough, it produces a high enough level of estrogen to give positive feedback to the hypothalamus. Further GnRH is released, promoting preferential LH release downstream, until an LH surge is triggered, giving us the ovulation event on day 14.

  • After this, the levels of LH and FSH decline in response to negative estrogen feedback, in the luteal phase of the ovary.

  • Simultaneously, the estrogen produced by the dominant follicle in the ovarian follicular phase above causes downstream effects on the endometrium, marking the proliferative phase here of endometrial growth in preparation for implantation.

  • Once the follicle releases the oocyte, the follicular cells become the corpus luteum, which then produces progesterone. Progesterone matures the endometrium to be ‘pro-gestational’ for implantation and the secretory phase of endometrial maturation occurs.

  • If no fertilization event occurs, the corpus luteum degenerates, and by day 23-25, progesterone withdrawal results in shedding of the endometrial lining. If a fertilization event occurs, beta-hCG prompts the corpus luteum to continue to make progesterone.

Further reading from the OBG Project:
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Managing AUB-O
PCOS: Making the Diagnosis

Polycystic Ovarian Syndrome (PCOS)

Big shout out to Andrey Dolinko, MD, who suggested today’s topic!
ACOG PB 194 is an excellent resource for your studying on PCOS (membership required).

PCOS is a syndrome, diagnosed clinically by at least 2/3 of the Rotterdam criteria:
1. Hyperandrogenism - hirsutism, male pattern baldness.
2. Oligo- or amenorrhea - 3+ months without menses.
3. Polycystic ovaries on ultrasound - 12+ follicles or increased ovarian volume.

In terms of treatment, the big take home message is to understand whether your patient is planning on pregnancy or not. CHCs are the mainstay therapy of patients not desiring pregnancy due to their multimodal method of action - regulation of HPO axis, increased SHBG, and endometrial protection. Also remember metformin (insulin sensitization) and spironolactone, finasteride, or flutamide (anti-androgens) as other adjuncts in patients not desiring pregnancy.

In those desiring pregnancy, oftentimes the complaint will be infertility. While letrozole is now preferred for ovulation induction over clomiphene due to a higher live-birth rate, letrozole does not yet enjoy FDA approval. For the other symptoms of PCOS in patients desiring pregnancy, the first line therapy is lifestyle modification! The literature doesn’t support metformin for ovulation induction, but some may use it for its other benefits prior to pregnancy.

We didn’t discuss laparoscopic ovarian drilling in this episode, but that would be another surgical treatment for PCOS-related infertility.

Diagnosis and Workup of Secondary Amenorrhea

Today's topic will be a follow up of last week: diagnosis and workup of secondary amenorrhea. This will be a broad overview, with much more detail to follow in the future! 

Again, the ASRM guidelines for amenorrhea are a helpful resource for further reading.

Additionally, the American Academy of Family Physicians (AAFP) has a guideline publication on amenorrhea. While it’s a bit outdated, they do supply a chart that can be a helpful framework for your studying or diagnostic evaluation!

And remember… did you get that pregnancy test yet?

Diagnosis and Workup of Primary Amenorrhea

Today's topic will be a broad overview of the diagnosis and workup of primary amenorrhea... There’s a lot to take in, but don't worry! There will more to come on each of the topics that we touch on down the line. 

Fei has made a handy chart for thinking about primary amenorrhea below!

For further reading on primary amenorrhea, see the ASRM guideline on amenorrhea.
And remember… always check a pregnancy test.