• Nathan Riley, MD

Beloved Holistics Radio Episode 82 - Management of AUB Associated W/ Ovulatory Dysfunction

Updated: Aug 15

"She is so bright and glorious that you cannot look at her face or her garments for the splendor with which she shines. For she is terrible with the terror of the avenging lightning, and gentle with the goodness of the bright sun; and both her terror and her gentleness are incomprehensible to humans.... But she is with everyone and in everyone, and so beautiful is her secret that no person can know the sweetness with which she sustains people, and spares them in inscrutable mercy.” ― Hildegard von Bingen

PB#136 - Published July 2013 (Reaffirmed 2017)

Five Pearls

  1. Know your reproductive endocrinology like the back of your hand!

  2. AUB-O is classically associated with cycles that differ in length by `10 days or more. Patient with AUB-O also generally don't experience the classical cyclical breast tenderness, mucoid cervical discharge, premenstrual cramping, or bloating seen in ovulatory bleeding.

  3. Anovulation is the most common etiology of AUB in 13-18-year olds. Transfusion or hospitalization is rare in this age group, but, when it happens, you should investigate coagulopathy.

  4. AUB-O in patients >18 years of age should prompt investigation for hyperplasia/malignancy.

  5. Hysterectomy or hormonal contraceptives are the mainstays for treating AUB-O, but neither address the underlying endocrine abnormality.

  6. SIS + EMB is a sweet combo: if both are negative, the likelihood of pathology is extremely low and conservative measures are be offered without you losing sleep

Abnormal uterine bleeding (AUB) and its etiologies

- recall the PALM-COIEN system:

Source: Malcolm Munro, MD, and friends

Little review of the female endocrine system...

- estrogen is produced by the ovarian follicles as they develop under the influence of FSH from the pituitary (follicular phase)

- progesterone is produced by the corpus luteum after ovulation (luteal phase)

- if conception doesn't occur, the corpus luteum disintegrates, and progesterone production ceases

- the abrupt drop in progesterone leads to a shedding of the endometrium, as the presence of progesterone support the thickened endometrium that was stacked up during the follicular phase under the influence of estrogen

- a disruption anywhere along the hypothalamic-pituitary-ovarian axis may delay or suspend ovulation altogether (see Box 1)

- unopposed estrogen allows the lining to build up unchecked --> may lead to hyperplasia or malignancy!

- AUB-O is the result of the endometrium spilling over without the "binding" properties of progesterone

The follicular phase varies in length; the luteal phase (after ovulation) is 14 days long) (Source:

How is AUB-O diagnosed?

- careful history, including age of menarche, details about her cycles, and pregnancy history

- normal cycles are 21-35 days in length (cycle = first day of your bleed to first day of subsequent bleed)

- remember pregnancy test!

- other labs: TSH and prolactin (ideally in fasted state)

- must rule out AUB-L and AUB-P --> start with ultrasound, but saline-infusion sonohysterogram (SIS), hysteroscopy, or even MRI can further elucidate structural causes of bleeding

- she doesn't report the classical cyclical breast tenderness, mucoid cervical discharge, premenstrual cramping, or bloating? likely AUB-O

- cycles differ in length by `10 days or more? likely AUB-O

Note: if all signs are pointing to AUB-O, but medical therapy doesn't fully control bleeding, you should consider AUB-M or AUB-C (do an EMB if suspected!)

Special considerations for 13-18-year olds

- AUB-O is most likely etiology of AUB in adolescence due to immaturity of hypothalamic-pituitary-ovarian axis (still consider your full differential, though)

- AUB-M is highly unlikely in this age group

- don't miss coagulopathy concurrent with AUB-O! (vWD is most common coagulopathy)

- obesity is also a factor: excess estrogen leads to anovulation through feedback to the brain

- bleeding in this age group is rarely sufficiently heavy to require hospitalization or transfusion (but never say never!)

- 20-30% of patients in this age group who require hospitalization or transfusion have an underlying coagulopathy

- you must also consider: pregnancy, sexual trauma, and sexually transmitted infections

- medication and progestin-only therapies like progestin IUDs are also dyn-O-MITE!

- in the case of severe, continuous COCs recommended along with iron supplementation until anemia resolves, at which you can switch to cyclical COCs

- low dose COCs (20-35 mcg ethinyl estradiol) can also minimize symptoms like hirsutism and acne seen in PCOS

Special considerations for 19-39-year olds

- PCOS is common, it presents with: noncyclical bleeding, signs of hyperandrogenism, and the appearance of polycystic ovaries on ultrasound

- often associated with obesity

- consider endometrial hyperplasia (meaning: EMB) if PCOS suspected (or if your patient is obese with a 2-3 year history of AUB), especially if inadequate response to medical therapy

- if EMB is non-diagnostic, SIS or hysteroscopy may be appropriate

- risk of endometrial cancer age 20-34 is 1.6%; age 35-44 is 6.2%

- COCs and progestin-only methods are reasonable

Note: For any obese patient with AUB-O, sustained weight loss through lifestyle modification should be a mainstay of therapy. Send them to my website...

Special considerations for women 40-years old up to menopause

- usually do to normal menopausal transition, but important to rule out hyperplasia/malignancy (although absolute risk remains quite low until age 45)

- as the number of follicles decreases, estrogen/progesterone levels become less regular

- still, you should consider pregnancy

- premenopausal use of hormonal therapy will not provide menstrual regularity or contraception (hormonal contraceptive is your best best)

- COCs and non-cyclical (non-IUD) progestin therapies can also help with vasomotor symptoms

Recall: Perimenopause begins when cycles become irregular. It's officially menopause when 12 months have passed without a bleed, which takes ~4 years for U.S. women. Mean age 51.4.

Treatment of AUB-O: general principles

- therapy depends on patient's goals: stop the bleeding indefinitely? desire for future fertility?

- treating surgically will stop the bleeding but it doesn't address the underlying endocrine abnormality

- treatment with hormonal contraceptives will help to stop the bleeding but likewise doesn't address the underlying endocrine abnormality

- combined oral contraceptives (COCs) include estrogen-progestin pills, "the patch", the intravaginal ring, : great as long as the patient doesn't have any contraindications (check the US Medical Eligibility Criteria for Contraceptive Use)

- progestin-only contraceptives include depot medroxyprogesterone (DMPA), oral medroxyprogesterone acetate (Provera), levonorgestrel-releasing intrauterine systems (progestin IUDs), norethindrone acetate (Nora-Be)

Surgical treatment

- hysterectomy or endometrial ablation are your two options

- either are only recommended if medical therapy fails

- endometrial ablation carries the risk of reduced future ability to detect endometrial cancer (i.e. EMB, hysteroscopy, etc.); this is important because if ablation is used for management of AUB-O, the underlying endocrine abnormality hasn't been corrected

- other potential adverse events associated with ablation include: post-ablation Asherman syndrome, synechiae, cervical stenosis, and endometrial distortion

- if signs/symptoms of endometrial cancer arise in the future post-ablation, hysterectomy is indicated

- in comparing hysterectomy with medical management, patients who underwent hysterectomy reported greater satisfaction than those managed through medical therapies (though satisfaction compared favorably to those who are managed with progestin IUD)

How useful is office EMB?

- sensitivity for detecting endometrial cancer is 68-78% (depends on whether the malignancy is diffuse or focal)

- only samples 4% of the endometrium on average

- potentially even worse utility in postmenopausal women, as it's especially hard to get an adequate sample (so atrophic!)

- if the EMB result is discordant with your suspicion or other workup (i.e. suspected polyps on SIS), get a better sample through D&C or hysteroscopy

- likelihood of endometrial cancer is 0.5% if hysteroscopy is negative

How useful in transvaginal ultrasound?

- less sensitive than biopsy in evaluating the endometrium

- best if performed 4-6 days into the menstrual cycle when the endometrium is thinnest

- SIS has far better sensitivity and negative predictive value for evaluating for endometrial pathology

- SIS + EMB is a sweet combo: if both are negative, the likelihood of pathology is extremely low and conservative measures are be offered without you losing sleep


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