Progestins

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Today we welcome Dr. Ben Brown, who is an assistant professor in the Division of Emergency Obstetrics and Gynecology at Women and Infants Hospital and the Warren Alpert Brown School of Medicine. Dr. Brown is also completed a fellowship in Family Planning, and thus shares with us his expertise in progestin-based contraception!

We quickly reviewed initially that progesterone naturally serves as an inhibitory feedback to luteinizing hormone during the menstrual cycle. There were also a number of downstream effects of progesterone, including cervical mucus thickening, stabilizing the endometrial lining, and down-regulating both systemic progesterone and estrogen receptors — you can review all of these again with our episode on the menstrual cycle if you missed it. These mechanisms of action underlie the way progestins work clinically. We do not cover the anti-progestins (mifepristone) and selective progesterone receptor modulators (ulipristal) today.

We then reviewed the generations of progestins. As Dr. Brown states, knowing drosperinone as a 4th generation is probably a good thing, but otherwise some of this is just good to know as a “contraception nerd.” The generations are summarized below in a nice table:

We then spoke about the delivery methods beyond the drugs — pills, injections, IUDs, implants, and more!

Side effects and contraindications are important to know for all forms of contraception. Here are a few that we review:

  • Androgenicity: more apparent in combined-hormonal methods, due to upregulation of SHBG by estrogen. Some progestins (particularly 1st generation) also competitively bind androgenic receptors — even sometimes if given without estrogen, those progestins may actually produce androgenic side effects! That said, this is quite uncommon.

  • Thrombosis: this can be very confusing and controversial:

    • Estrogen-containing methods will raise risk of both venous and arterial clots.

      • Drosperinone and other later-generation progestins has received poor press due to higher risk of thrombosis in combined formulations. The risk is overall still very low: 7-13 events per 10,000 woman years. But compared to pregnancy as a competing outcome, 20-30 events/10k woman years, and postpartum 40-60/10k woman-years!

    • Progestins alone can also raise arterial thrombus risk.

      • These are patients who you consider to have significant endovascular risk factors — longstanding poorly-controlled diabetes, coronary disease, heavy smoking, etc. This is because progestins can shift lipid profiles to a more androgenic appearance - lower HDL, higher LDL and total cholesterol.

    • The CDC’s US MEC guidelines are an excellent tool to cross-reference comorbidities against contraceptive methods.

  • Breast cancer: current or prior is a relative contraindication to hormonal contraception.

  • Severe liver disease: contraindicated due to impaired hepatic processing of steroid hormone.

  • Bariatric malabsorptive procedures: may not be great candidates for progestin-only pills due to need for consistent dosing time.

The Menstrual Cycle

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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:

Wikipedia

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

Osteoporosis

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Today’s episode was recommended by @KatieSmithMD on Twitter. Thanks, Katie!

Did you know there was a Practice Bulletin about osteoporosis? We didn’t either, but ACOG PB 129 is excellent reading though! (ACOG membership required)

We don’t touch much in the podcast on “secondary osteoporosis,” that is osteoporosis due to other medical conditions. There are a number of things that can predispose women to this that you should also keep in mind, especially if the patient has a particularly low Z-score (score relative to others their age), or if you have a younger postmenopausal woman who experiences a fracture.

ACOG PB 129

There are also a number of medications that you can use to treat osteoporosis, reviewed extensively in PB 129. However, likely highest yield for your practice and for CREOGs are Calcium and Vitamin D requirements for women based on age:

ACOG PB 129

Finally, be familiar with the FRAX score, and when to initiate workup of osteoporosis in the postmenopausal patient. The flowchart below also comes from PB 129. Didn’t we say it makes for some excellent reading?

ACOG PB 129

Diagnosis and Workup of Primary Amenorrhea

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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.