Abnormal Uterine Bleeding: The Basics

Today we talk through the varied etiologies and a basic workup for a common GYN complaint: abnormal uterine bleeding. ACOG PB 128 makes for good companion reading for women of reproductive age.

The terminology of AUB has changed quite a bit, and you may still hear older terms being used. “Dysfunctional uterine bleeding” or DUB has fallen out of favor, as have terms such as metrorrhagia or menorrhagia, yielding instead to simpler terminology such as prolonged menstrual bleeding and heavy menstrual bleeding, respectively. The terms such as oligomenorrhea (bleeding cycles > 35 days apart) and polymenorrhea (cycles < 21 days apart) are also in use to some degree.

Heavy bleeding is difficult to discern, but for research purposes has been described as >80cc blood loss per cycle. In clinical practice, this is obviously impractical, so we rely on subjective descriptions of heavy bleeding to guide care.

The biggest takeaways from this episode include the PALM-COIEN classification of bleeding by FIGO, as well as the common culprits of bleeding by age group. Remember also the criteria for working up for disorders of coagulation, which we’ve put here (though contained in the practice bulletin).

Stay tuned for future episodes about the treatments of these various etiologies, or check out our friends at The OBG Project for excellent summaries of guidelines and new literature!

ACOG PB 128

ACOG PB 128

ACOG PB 128

Progestins

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

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:
Get updates on this and more content, as well as other awesome features for FREE if you’re a PGY-4 — sign up for OBG First!
Managing AUB-O
PCOS: Making the Diagnosis