Espresso: Acute Uterine Bleeding

What causes bleeding?

Remember - PALM-COEIN! We talked about this way back in episode 47. As a quick refresher:

PALM - the structural causes:

• P - polyp

• A - adenomyosis

• L - leiomyoma (fibroids)

• M - malignancy

COEIN - the non-structural causes

• C - coagulopathy

• O - ovulation (i.e., anovulatory)

• E - endometrial (local endometrial factors)

• I - iatrogenic 

• N - not otherwise specified

Your EM colleagues call you STAT! It’s really bad! What should you do?

• Start ABCs! 

  • Get your vital signs - assess for signs of hemorrhagic shock

  • IV access - 2 large-bore if possible

  • Resuscitate - balanced crystalloid is a good place to start if relatively stable; blood if appearing unstable 

• Laboratories:

  • Pregnancy test

    • Remember, pregnancy heavy bleeding opens up a whole new can of differential diagnosis and management -- from miscarriages to retained placental fragments.

      • We’ll set that aside for today.

  • CBC - know where you’re starting from. 

    • Note that with an acute bleeding episode, H/H may not accurately reflect actual RBC status as there hasn’t been time to equilibrate.

    • CBC may also clue you into rarer disorders -- i.e., thrombocytopenia due to TTP-HUS or leukemia -- that may result in vaginal bleeding.

  • Coag panel - do you suspect coagulopathy?

    • In the adolescent patient, this may be sign of underlying bleeding disorder like von Willebrand’s disease or hemophilia. 

    • In an older patient without history of bleeding, abnormal coags may point to evolving DIC from very significant bleeding, or acquired coagulopathy (i.e., overdose with warfarin).

  • Type and screen/crossmatch - get blood ready! 

    • A type and screen is always a good place to start, and will be the test that takes the longest.

      • Assuming no antibodies to screen against, a crossmatch can then be had relatively quickly in most large medical centers.

• History & Exam:

  • History should be directed towards understanding how much, how long, and how frequently.

    • How much - get a sense for the amount of acute blood loss, and whether this is life threatening.

    • How long - understand timing of the bleeding as another marker of amount of blood loss, and how long the episodes have lasted if they have happened in the past.

    • How frequently - understand if this is a one-off acute event versus a recurrent issue.

      • Frequent heavy bleeding events may be suggestive of underlying bleeding disorder in younger patients, versus structural causes of heavy bleeding (i.e., fibroids) in older patients. 

    • Examination may help point towards cause immediately - trauma, prolapsing fibroid/polyp. 

      • Also, exam should help increase or ease your suspicion for life-threatening hemorrhage based on what you find!

    • Imaging and other testing may be warranted:

      • Imaging if patient is stable, and suspect but need to diagnose underlying cause (i.e., pelvic ultrasound)

      • Consider endometrial biopsy in those under age 45 with risk factors (unopposed estrogen).

How do I stop the bleeding?!?!

Medical therapy is most ideal in the moment, though surgical therapy is occasionally required! 

Meds to remember:

• Conjugated equine estrogen (IV estrogen). 

  • Source: equine (horses)

  • Dose: 25mg IV, every 4-6 hours for 24 hours

  • Avoid in patients with breast cancers, history or risk of thromboembolic disease,

  • Efficacy: excellent

    • Small RCT demonstrated stoppage of bleeding in 72% of women with exposure to IV estrogen over 8 hours (vs 38% with placebo).

  • Requires observation/inpatient administration as IV only, and will ultimately need to transition to a PO medication (can’t use unopposed estrogen forever!)

• Combined oral contraceptives

  • Suggested dose: 35mcg monophasic combined pill, TID x 7 days.

    • Many alternative regimens that are discussed, likely one exists that is a favorite at your hospital.

  • Avoid in patients who are smokers age 35+, history of or current VTE, migraine with aura, or other major risk factors for VTE (diabetes with vascular complications, recent surgery with immobility, etc).

  • Easy to administer, and patients are generally familiar with OCPs.

  • Side effects generally include nausea from high amount of estrogen - consider coprescription with antiemetic.

  • High efficacy -- 88% stop bleeding within 3 days.

• Medroxyprogesterone acetate (Provera)

  • Suggested dose: 20mg PO, TID x 7 days

    • Like COCs, many alternative regimens exist, and likely one is a favorite at your hospital.

  • Similar contraindications: avoid in those with past/current history of DVT/PE, breast cancer, or liver disease.

  • High efficacy -- 76% stop bleeding within 3 days.

  • May have improved side effect profile over COCs (less nausea)

• Tranexemic acid

  • Dose: 1300mg PO TID x 5 days; alternatively, can use IV formulation at max 600mg q8h.

  • Uncertain thromboembolic risk, but follows again that may increase this risk so use with caution in those with significant risk factors.

  • Reduces bleeding in those with chronic AUB 30-55%.

Bleeding disorder suspected?

Get hematology involved! Resuscitation / treatment may be influenced by particular factor deficiencies.

Surgical management

• D&C, hysteroscopy, etc.

  • May be helpful for known causes (i.e., polyp, submucosal fibroid) but are often just temporizing measures otherwise.

  • Unless cause is truly identified, will not necessarily impact bleeding beyond the current cycle.

• Balloon tamponade

  • On the small, nonpregnant uterus, use a 26F Foley catheter with 30cc saline in the balloon.

• Interventional radiology for uterine artery embolization; hysterectomy

  • These can be considered as options, though ideally not in the mega-acute situation. More ideal to have some planning involved first!

Evidence-Based GYN Surgery

Check out: https://www.ajog.org/article/S0002-9378(18)30583-0/fulltext

Remember the evidence-based C-section? Turns out, there is also good evidence for gyn surgery practices!

Preoperative - Includes things that are part of the ERAS protocol

1. Patient Education 

   • Two randomized control trials 

   • There was some potential association between preoperative patient education and improved outcomes (low level evidence) —> perhaps some decrease in length of stay and pain.

2. Bowel Prep

   • Minimally invasive gyn surgery:

     • Strong evidence that oral mechanical bowel prep should not be used.

   • In those with high risk of colorectal resection:

     • Based on colorectal surgery evidence, oral mechanical bowel prep alone is not effective 

     • Use of one of the following regimens can be considered: (moderate level evidence) 

       • Oral bowel prep AND oral antibiotic 

       • Oral antibiotic alone

3. Surgical site infection bundles - high level of evidence

   • High level of evidence - use of surgical site infection bundles should be considered! 

     • Listen back to our episode on “Infection Prevention and Gynecologic Surgery”: https://creogsovercoffee.com/notes/2019/10/13/infection-prevention-and-gynecologic-surgery

     • Sometimes, it’s not always just a single thing, but the whole bundle!

4. Glucose management 

   • Goal of <180 mg/dL (high level of evidence) 

5. Diet

   • Reduce fasting - may ingest solids until 6 hours prior to anesthesia induction and clear liquids until 2 hours prior to induction 

     • High level of evidence 

   • Carbohydrate loading - routine carbohydrate loading is recommended (moderate level of evidence) 

     • May ingest 2-3 hours up to induction of anesthesia - can include things like apple juice, ensure clear, etc. 

6. Pre-anesthesia medication 

   • Pain:

     • Combination of acetaminophen, COX-2 inhibitor (celecoxib, for example), and/or gabapentin - level of evidence is high!

   • Nausea:

     • Scopolamine, midazolam, or gabapentin (high level of evidence) 

7. VTE prophylaxis - moderate evidence 

   • Overall low rates of VTE in general, but preoperative intermittent pneumatic compression alone for patients undergoing MIS or laparotomy for benign disease

   • Weak evidence from observational studies supports adding preoperative pharmacologic prophylaxis for patients undergoing laparotomy for gynecologic malignancies  

Intra-operative 

1. Drains 

   • Routine NG tube - associated with patient discomfort and no known benefit (high level of evidence) - from the ERAS Society 

   • Routine peritoneal drains - not recommended routinely in gyn or onc surgery including cases with lymphadenectomy or bowel surgery

     • 2017 Cochrane Database showed drainage was not associated with reduced rates of lymphocyst formation. However, use of surgical drains increased rates of symptomatic lymphocyst formation when the pelvic peritoneum was left open 

     • Overall, moderate evidence  

2. Antibiotic prophylaxis

   • Given within 1 hour prior to incision per CDC and ACOG; redose prophylactic antibiotics for long procedures (ie. Ancef 3-4 hours after incision)

     • Level of evidence is high

3. Skin prep

   1. Ideally use 2% chlorhexidine and 70% isopropyl alcohol solution (high level of evidence) 

4. Blood transfusion (for hemoglobin 6-10) and fluids to maintain intraoperative euvolemia

5. Maintain normothermia 

6. Pain management - liposomal bupivicaine for laparotomy cases (moderate)  

Postoperative

1. Early mobilization - moderate level of evidence 

   • Has been shown to be beneficial and to avoid prolonged bedrest; basically meaning out off bed and mobilizing within 24 hours of surgery 

     • Reduces PEs and VTEs, also may protect against muscle atrophy and deconditioning 

2. Early alimentation 

   • Postoperative feeding - within 24 hours of surgery (can be as early as 4 hours after surgery with or without bowel resection) 

   • Two systematic reviews and 1 meta-analysis - early feeding is safe, well-tolerated and results in earlier return of bowel function and shorter LOS 

3. Early urinary bladder catheter removal (mod level evidence) 

   • Catheter use for < 24 hours, but appropriate to consider fall risk and necessity of urine output monitoring 

   • Uncomplicated surgeries: consider removal at 6 hours to balance rate of infection vs retention 

   • Complicated: morning after may be more appropriate (ie. urogyn or gyn onc cases) 

4. Prevention of ileus and accelerate return of bowel function

   • Use of postop laxatives (recommended for gyn surg, low level of evidence) 

     • Docusate sodium (Colace): more about its lack of utility here.

   • Chewing gum (high level of evidence) 

   • Alvimopan (novel peripheral u-opioid antagonist) - may not be beneficial in benign gyn 

     • However, may decrease ileus in ovarian cancer surgery and can be considered for use in patients undergoing bowel resection  

5. Early IV fluid discontinuation 

   • Discontinue maintenance IV fluids within 12-24 hours following surgery, especially with early PO intake (low level of evidence) 

     • Urine output as low as 20 mL/hour

       • Can be normal post op stress response 

       • Intervention not required 

6. Postoperative VTE: 

   • Mechanical prophylaxis for duration of hospitalization in all gyn surg patients 

   • Mechanical and/or pharmacologic prophy for gyn onc surgical patients (high level of evidence) 

     • Additionally, for oncology cases with laparotomy, should extend VTE prophylaxis for 4 weeks following surgery 

Pediatric Vulvovaginitis

Infrequently in the general gynecologist’s office, you may be asked to evaluate a child for concern of vulvovaginitis. Today’s episode will review some common questions regarding approach in pediatric gynecology, and be specific to a pre-pubertal population.

Many times this is the first time that the young patient has seen a gynecologist! It’s going to be a scary and unfamiliar environment, as the only context for physicians for many children at this point are their pediatrician or family physician. You’ll likely have to lean in to the parent/close relative/guardian for history and more information regarding chronicity, anxieties, and specific complaints.

Common complaints can include:

• Itching or discharge.

• Pain or irritation.

• Issues with going to the bathroom (ie. some children may have issues of leaking urine, seemingly losing the developmental milestone of urinary continence).

The approach in pediatrics is somewhat different:

• Getting the trust of the patient - this may be harder for us as Ob/Gyns, since we are not always used to dealing with a pediatric population.

  1. Stickers, coloring books, asking about school and friends etc.

• If they are old enough to speak for themselves, always ask them what’s going on!

• Then ask/tell them that you are going to talk to their parent/guardian who is with them that you’d like to ask them as well what is going on — this is respectful of the child and keeps them involved.

• For adolescent patients, usually have the parents/guardian step out of the room for some time for sensitive questions 

  1. Assess risk: safety at school, home, people they don’t get along with or who may be hurting them 

  2. Drug/alcohol/tobacco use - kids may feel guilty about using. Ask if friends/family use, then can broach the subject with them.

  3. Sexual activity (usually approached with “Do you have anyone at school that you might like? Have you held hands or kissed them?).

Specific questions related to the complaint:

• Assessment of vulvar hygiene

  1. Showering/bathing habits - bubble baths? What types of soaps? 

  2. Toileting - how do they wipe? Have them demonstrate 

  3. Choice of clothing/clothing due to hobbies/activities - leotards, tights, swimsuits, etc - how long are they wearing them during the day? What kind of underwear? What about pajamas? 

• The exam

  1. Most children will not have had a pelvic exam, and most (read: almost all) do not require a speculum exam!

  2. Check for abnormal breast development (ie. early breast development) in younger children.

  3. Check for abdominal masses.

  4. Pelvic exam:

     1. Child can be laid back on the table in frog leg position, can also have parent sitting on exam table and holding child on lap in this position.

     2. Careful external examination, also can spread labia from lower legs/bottom and look at urethra/hymenal ring.

        1. Look for skin changes on the labia - red? White? Thin? 

        2. Also, see if there is labial adhesions.

        3. Purulent discharge/other types of discharge can be seen on underwear as well 

     3. Q-tip test to evaluate for vaginal potency.

     4. Foreign objects that cannot be easily removed should not be done in the office with smaller children, may require vaginoscopy  

Now let’s review some differential diagnoses that may present in young children.

Infectious 

1. Candida 

   1. Possible to have yeast infection in children who have had recent antibiotic treatment or if they wear diapers.

   2. Usually uncommon in normal prepubertal girls, unlike in women.

   3. If mostly on the outside, or diaper dermatitis, can use topical antifungal agents like nystatin, clotrimazole, miconazole, etc.

2. Gardnerella - also possible, but it is not common. Treat like BV. 

3. STI - suspect if purulent discharge with evidence of sexual abuse on interview/exam

   1.  Evidence includes anal or genital tears, evidence of ejaculation.

   2. Laceration to lower half of the hymenal ring, usually 3-9 o’clock is consistent with penetrating injury.

   3. Suspicion of child abuse is something that requires mandatory reporting to authorities.

   4. Things to test for include gonorrhea, chlamydia, trichomonas.

   5. Genital warts: can be diagnosed clinically and usually with biopsy.

Noninfectious 

• Foreign body

  1. Can cause acute and chronic vulvovaginitis with purulent discharge, foul smell, and even bleeding.

  2. Most common things are toilet paper, small toys, etc → can usually be removed with warm vaginal lavage (ie. obtaining thin catheter and attach to 60cc syringe). Place the tip of catheter into the vaginal canal, and can lavage several times 

  3. Can treat introitus with small amount of Xylocaine jelly if needed for pain / local anesthetic.

  4. If large object or not easily removed, may need sedation/anesthesia for extraction.

  5. If there is suspicion for battery within the vagina, this is a reason for anesthesia, vaginoscopy for possible burns 

• Trauma 

  1. Vulvar trauma can cause significant bleeding - area is highly vascular 

  2. Interview is important - was there recent straddle injuring/skating injury?

     1. History should correlate with physical finding - otherwise suspect abuse.

  3. Straddle injury: injury usually anterior area of the vulva, including mons, clitoral hood, and anterior aspect of the labial 

     1. Should not have injury to the posterior fourchette and hymenal areas - this would suggest sexual abuse.

     2. Assess ability to urinate and presence of hematoma; if unable to urinate,, need to drain bladder, ice, and give pain medication if large hematoma.

        1. If not obstructive, can ice and give pain medication. Most hematomas will resolve spontaneously 

     3. Surgery is rarely needed and can result in introduction of skin → infection 

Skin issues 

• Lichen sclerosus 

  1. We talked about lichen sclerosus in postmenopausal women previously!

  2. It can cause itching, discomfort, even discharge.

  3. Usually appears white, thin skin (onion skin, cigarette-paper), and usually around the vulva and perianal regions.

     1. Can usually diagnose with visual inspection, and biopsy is rarely needed, though in adults you should biopsy (can be associated with malignancies in adulthood).

  4. Treatment: superpotent topical steroids → first start with more frequent treatment, then maintenance therapy.

• Labial adhesions

  1. Most frequently in infants and young children, peak incidence up to 3% in second year of life in girls.

  2. Usually due to inflammation + low estrogen.

  3. Can lead to discomfort and possible issues with urination, recurrent urinary tract infection.

  4. If asymptomatic, no treatment is necessary especially if it only involves a small portion of the labia.

  5. If symptomatic - initial treatment with topical estrogen/estradiol cream twice a day with fingertip or Q-tip, sometimes with a little pressure, but do not try to manually separate the adhesion as this can cause tearing/pain/bleeding.

     1. Usually can see a thin, translucent raphe in the middle (location of placing estrogen) 

     2. Another option is topical betamethasone as alternative or adjunctive topical treatment  

  6. Surgical separation - rarely indicated. Usually only for those with severe obstruction to urinary flow or who have urinary retention. 

• Vulvar ulcers 

  1. Can be non-sexually transmitted ulcers and can present with systemic symptoms like fatigue, malaise, fever, etc.

  2. Etiology may not always be determined, but viruses can sometimes cause them (ie. flu A, EBV, mycoplasma, CMV).

     1. Take a careful sexual history to rule out other STDs, HSV - but perform these tests as well just in case.

  3. Can also test with CBC and monospot test.

  4. If continues to be painful, unable to urinate, some girls may need to be admitted for pain control and foley placement.

  5. Other things to rule out: Behcet’s syndrome (if chronic ulcers), Crohn’s disease.

Nonvaginal issues 

• Urethral prolapse

  1. Distal end of the urethra can prolapse either partially or in a complete circumferential fashion (“donut-like”).

  2. Tissue can be friable and can become infected.

  3. Usually will have pain with urination, bleeding, etc. 

  4. May need to differentiate from other things like sarcoma botryoides or prolapsed ureterocele (may need a urologist!).

  5. If symptomatic, can be treated with topical estrogen 2x/day for two weeks, and then reassess.

• Pinworm 

  1. Can cause vulvar symptoms as well, like itching, but usually is perianal itching.

  2. Caused by the worm enterobiasis.

  3. Can be diagnosed with visual inspection or “paddle test” where there is a plastic paddle sometimes with adhesion pressed to perianal area → then place on glass slide to see worms.

  4. Treatment is with albendazole or mebendazole, and should think about treating the entire household.

  5. Wash all bedding and clothes!

Benign Vulvar Dermatoses

So back in December 2019 (episode 66), we talked about vulvovaginal itching and gave a broad differential for workup of this very common symptom. Today, we thought we might focus on a few of the commonly tested and supremely confusing vulvar dermatoses, based on the new ACOG PB 224.

A quick refresher on diagnosis and workup: 

• History and physical are supreme in helping you establish acute vs. chronic and narrowing down most likely suspects.

• Labs beyond a wet mount are usually not needed, unless suspecting immunocompromise or needing a genital culture for persistent vaginitis symptoms.

• Biopsies in general are reserved for ruling out possible premalignant or malignant areas.

Lichen Simplex Chronicus (LSC)

• Chronic, nonscarring, inflammatory condition characterized by intense itch-scratch.

  • Most commonly reported symptom is chronic or intermittent intense itch, most commonly in the evening or night.

• Very common - accounting for up to a third of vulvar clinic visits, and often is a secondary condition of other “itchy” vulvar disease like contact dermatitis. 

• Most commonly encountered in middle aged women or elderly, and in women with a history of environmental allergies, asthma, or childhood eczema.

• On exam, appearance is often erythematous, scaling, and/or lichenified (thickened/leathery) plaques, with variable degrees of excoriation due to the intense itching associated with the condition. 

  • The skin with longstanding disease is often described as “bark-like” it’s so thick! 

• Consideration can be given to identifying other diseases that may be contributing to itching, such as candidiasis, but biopsy is not generally indicated.

• Treatment is multipronged:

  • Education on stopping the itch-scratch cycle.

  • Removal of offending/worsening factors, such as contact dermatitis, excessive heat/moisture, or treatment of infection.

  • Medium or high-potency topical corticosteroid, applied once or twice daily. If started on steroid, should be seen again within 4 weeks to assess response and adjust course. 

  • Oral anti-pruritic medications.

Lichen Sclerosus

• Chronic, scarring disorder that is bimodal in age distribution -- affects most commonly the anogential skin of prepubertal girls and postmenopausal women. 

• Often asymptomatic and goes unrecognized by many clinicians.

• If symptomatic, most common presenting symptoms include itching/irritation/burning, dyspareunia, and tearing.

• On exam, the skin often has the classic “cigarette paper” appearance - thin, whitened, and crinkled. 

  • Extensive involvement from the superior vulva to the perianal tissue may create an “hourglass shape” of involvement which is classic for this disease.

  • Due to the scarring nature of the condition, the introitus may be narrowed, there may be phimosis (inability to retract skin around) of the clitoral hood, and presence of fissures. 

• Biopsy is generally warranted in postmenopausal patients - patients with LS have increased risk of vulvar squamous cell carcinoma, ranging from 2-5%. 

  • Biopsy should be undertaken in areas which appear to be high risk -- i.e., if presence of any ulcers/erosions, or hyperpigmented or hyperkeratotic areas.

• Treatment of LS is important in order to halt and prevent further scarring. Initially, a high potency corticosteroid should be used, generally clobetasol propionate 0.05% or mometasone furoate 0.1%. 

  • Dosing / application schedule is not well studied, but the PB recommends nightly for 4 weeks, every other night for 4 weeks, and then twice weekly for 4 weeks.

  • Maintenance therapy is generally needed until puberty in girls, or lifelong in older patients, and should be the most infrequent dosing that maintains resolution. 

  • For disease not responding to steroids, it is most important to ensure the diagnosis is correct! You don’t want to treat VIN/ vulvar SCC with steroids. 

    • Intralesional steroid injections or topical calcineurin inhibitors such as tacrolimus can be used for particularly resistant disease, but consider vulvar specialist referral before you are doing these.

Lichen Planus

• Multisystem scarring dermatosis affecting the skin, oral mucosa, and vulvovaginal area, likely as a consequence of a dysfunctional cell-mediated immune system. 

  • Autoimmune disorders have been seen in up to a third of patients with LP.

• Rare, with incidence in general population less than 1%. 

• Most common in perimenopausal and menopausal women. 

• Common presenting symptoms are dyspareunia, burning, soreness, itching, and vaginal discharge.

• Diagnosis is complicated as there are multiple potential presentations; However, over 70% with vulvovaginal disease will also have oral involvement, so if suspected an oral exam should also be performed. 

  • Classic (papulosquamous): white, reticular, lacy, fernlike striae.

    • Dusty pink, poorly demarcated papules may also be present.

    • Occasionally with extensive involvement can “white out” vulvar skin and make picture confusing versus lichen sclerosus.

  • Erosive deep, painful, and erythematous lesions appear in posterior vestibule extending to labia minora. Architecture is often distorted and vaginal epithelium may be completely denuded. Lesions are extremely friable. 

  • Hypertrophic is the least common presentation, though with white, thick, warty plaques. 

• Wet mount performed for diagnosis will often demonstrate an abundance of immune cells in addition to parabasal and basal epithelium, as well as increased pH (5-6)

• Biopsy may be indicated based on the presentation, and may be helpful for distinguishing from rarer diagnosis like bullous pemphigoid / pemphigus vulgaris (ask your derm friends).

• Treatment is based on expert opinion but is high-potency topical corticosteroids, generally twice daily and tapered back over time. 

  • For erosive disease, also should be treated with intravaginal steroid therapy, such as hydrocortisone suppositories, and followed by vulvar specialist. 

  • Often will also need dilator therapy along with steroids due to scarring nature of disease. 

A quick word on topical corticosteroids

• So medium and high-potency corticosteroids feature heavily in the treatment of benign vulvar dermatoses… so review PB 224 for a list of them! 

  • Ointments are the preferred treatment compared to creams, lotions, or gels, as the ointments have the least additional additives that can make skin more sensitive and also allow for highest effective dose to penetrate the skin. 

View fullsize

ACOG PB 224

Fibroids

Fibroids, aka leiomyomas, are non-cancerous overgrowths of fibromuscular tissues within the uterine wall. They’re very common, affecting 20-80% of women by the age of 50 (depending on the population). Additionally, fibroids for 50% of women are completely asymptomatic.

Many patients will inquire about cancer risk with these benign “tumors,” particularly given the bad press around power morcellation. Fibroids in general do not increase one’s risk for malignancy; the risk of sarcomas in leiomyomas range between 0.05-0.28% (very rare).

Risk factors for fibroids include age (older > younger), black race, obesity, family history of fibroids, nulliparity, vitamin D deficiency, food additive consumption, and use of soy milk, strangely enough.

Fibroids are classified using a FIGO classification system based on their location:

View fullsize

So if fibroids half the time don’t cause problems, how and why do they cause problems?

The most common symptom of fibroids is heavy, prolonged menstrual bleeding. Fibroids do not necessarily rule out the risk of endometrial malignancy, so for those at risk, you should still do an endometrial cavity evaluation with EMB or hysteroscopy D&C. However, the bleeding from fibroids can be significant. The degree of bleeding is correlated often with the location of the fibroid, with size of secondary importance. Submucosal fibroids most frequently cause significantly heavy bleeding. Intramural fibroids can also cause this. Subserosal fibroids are rarely associated with heavy bleeding. How and why does this bleeding occur? It’s unclear, but may include abnormalities of uterine vasculature.

Another common symptom of fibroids are “bulk” symptoms. This is due to the size or location of a fibroid causing mass effect. This often manifests as pelvic pain/pressure that is chronic, intermittent, and dull; urinary tract or bowel issues such as frequency, difficulty emptying, or constipation; painful menses or intercourse; and venous compression rarely, similarly to a gravid uterus causing vena cava compression and increasing VTE risk. Clinically you might also see fibroid degeneration, where the fibroid has outstripped its blood supply and is necrosing, which leads to pain, leukocytosis, low grade fever, and uterine tenderness.

The final category of symptoms are reproductive issues. If a fibroid distorts the endometrial cavity, it may result in difficulty conceiving or increased risk of miscarriage. The links here are suspect as large, observational studies looking at these problems have many other confounding factors (i.e., increasing age). That said, fibroids have also been noted to have association with adverse pregnancy outcome as well, including placental abruption, fetal growth restriction, malpresentation, and preterm labor and birth.

Therapy options can be broken down into “expectant management,” medical treatment, and surgical treatment.  

For medical therapies, there are multiple options:

• Hormone therapies - really just to treat bleeding; doesn’t really help that much with other symptoms like bulk-related or reproductive issues.

  1. Combined estrogen-progesterone contraceptives - first line in treatment of AUB, but there is a high conversion rate to surgery in 5 year period.

  2. Levonorgestrel IUD - no randomized trials evaluating IUD for HMB related to fibroids. 

     1. There is a decrease in bleeding and increase in hematocrit in observational studies; however, distortion of cavity due to fibroid is a relative contraindication .

  3. Progestin treatments (ie. implant, injection, pills) - conflicting info about whether or not they can increase size of fibroid 

     1. Can be considered for treatment of mild symptoms especially in women that desire contraception 

  4. PRMs (progesterone receptor modulators) - not currently available in most countries

     1. Ulipristal acetate has been used outside the US, but stopped because of rare cases of liver toxicity; has been shown to decrease HMB 

     2. Mifepristone - not currently approved for treatment of fibroid; has been shown to reduce uterine volume by 26-74%, which is comparable to GnRH agonists! However, no availability in the doses that are used to treat fibroids (ie. 5-50 mg/day compared to 200mg for abortion) 

  5. GnRH agonists - most effective medical therapy for uterine fibroids; only available as injection.

     1. Initially increases release of gonadotropins, but then there is desensitization and downregulation to hypogonadotropic, hypogonadal state; a “medical menopause” if you will.

     2. Most women will develop amenorrhea or betterment of bleeding, and there is significant reduction of uterine size 

     3. Effect is temporary, and symptoms quickly return after you stop using it

     4. Can lead to menopausal issues due to hypoestrogenic state = Vasomotor symptoms, but also BONE LOSS

        1. Should not use for >6 months without add-back therapy: combined estrogen-progesterone or just progesterone in the form of 0.625 mg of conjugated estrogen and 2.5mg of medroxyprogesterone acetate or 5 mg norethindrone acetate);

        2. Usually GnRH agonists are used pre-operatively to shrink fibroid, as a “bridge” to surgery.

  6. GnRH antagonists - pretty new for this stuff! 

     1. Also induces hypoestrogenic state, but they are oral, not injections! Can lead to all the bad things that GnRH agonists can.

     2. The one available in the USA is Elagolix (Orilissa) 

     3. Also need add-back therapy if you want to use it long term.

  7. Aromatase Inhibitors - small studies show decrease in size of fibroids; not FDA approved 

  • Antifibrinolytic agents such as TXA are not well studied in HMB related to fibroids specifically, but is used for heavy bleeding in general.

  • NSAIDs - not extensively studied for HMB in fibroids; doesn’t decrease bleeding much, but can help with pain.

Surgical therapy is an alternative choice, particularly if medical management fails, or for bulk or infertility-related symptoms.  

• Myomectomy 

  1. Usually for people who aren’t done with childbearing or want to retain their uterus.

  2. Try and complete it minimally invasively if possible for decreased morbidity; this includes laparoscopically, robotically, or hysteroscopically if possible.

  3. Otherwise will need to do a laparotomy.

• Endometrial ablation 

  1. Purely for bleeding symptoms.

  2. However, some devices are only designed to be used in a normal cavity and not.a distorted cavity. Also, will not help with bulk symptoms.

  3. Relatively high rate of re-intervention for treatment failure.

• Uterine artery embolism 

  1. Can lead to shrinkage of fibroids 30-46%.

  2. However, those with larger uteri and/or fibroids are at higher risk of failure.

  3. Relatively high rate of re-intervention for treatment failure. 

• Hysterectomy 

  1. Suggested for women who are have severe hemorrhage not responsive to other treatments, done with childbearing and have other issues (like EIN, endometriosis, etc) that could be eliminated by hysterectomy, failed prior minimally invasive therapies for fibroids, or done with childbearing and want definitive treatment of symptoms.

  2. Main advantage: eliminates symptoms and any recurrent problems from fibroids.

  3. Morbidity may outweigh benefits if there is a solitary subserosal fibroid, a pedunculated fibroid, or a submucosal fibroid that is easily removed by hysteroscopy.

  4. Minimally invasive hysts should be pursued when possible to decrease morbidity.