Mastalgia

Mastalgia is breast pain. It’s a super common complaint, but one that we don’t spend a lot of time learning about in OB/GYN residency.  But a systematic approach and knowing a little bit of evidence makes this an easier problem to tackle!

There are 3 types of breast pain: cyclical, noncyclical, and extramammary 

Cyclical 

• Characterizes about ⅔ of patients with mastalgia.

• Associated with hormonal fluctuations of menstrual cycles, usually starts about a week prior to menses.

• Usually bilateral, most severe in upper outer quadrants.

• Caused by stimulation of ductal elements by estrogen.

• Can also be associated with pharmacologic hormonal agents (ie. OCPs, HRT).

Noncyclical 

• Represents ⅓ of women with true mastalgia.

• Does not follow a menstrual pattern.

• More likely to be unilateral or located in one position on a breast, etc. 

• Causes are highly variable:

  • Large, pendulous breasts;

  • Diet and lifestyle (high fat diet, smoking, caffeine intake);

  • Breast cysts; ductal ectasia (meaning distention of subareolar ducts due to inflammation unrelated to infection);

  • Mastitis;

  • Inflammatory breast cancer;

  • Hidradenitis suppurativa;

  • Mondor’s disease (thrombophlebitis of the breast);

  • Trauma;

  • Certain medications, such as some SSRIs and antipsychotics, as well as spironolactone.

Extramammary - not a “true mastalgia.” 

• Basically referred pain from the intercostal nerves, or chest wall pain likely due to muscular injury.

How common is mastalgia, and what are risk factors? 

• Very common - up to 70% of women in the US will experience some type of mastalgia in their life.

• Those at higher risk are older women, those with larger breast size, less fit and/or physically active.

How do you approach the evaluation of mastalgia? 

1. History characterizing questions are super important with mastalgia! They can help to elicit the differences commonly seen between the cyclical and non-cyclical types, as well as find other potential causes of pain that are not true mastalgia.  

   • Where is the pain? Is it bilateral or just on one side? 

   • What does the pain feel like? Aching? Pinching? 

   • When does the pain occur? Does it occur around your period? 

   • Do you take any hormonal medications? 

   • Is it associated with other types of pain, like neck, back or shoulder pain? 

   • Have you had a fevers/chills/systemic symptoms? 

   • Have you had any recent trauma to the chest? 

   • Does the pain affect daily function? 

   • Complete medical, surgical history etc. 

2. Physical the breast exam can help to rule out any obvious causes, such as infection, mass or malignancy.

   • Examine for evidence of malignancy: mass, skin changes, or bloody nipple discharge.

   • Make sure you examine all 4 quadrants of the breast as well as the chest wall.

   • May have to have the patient lay on their side to be able to examine the chest wall when the breast falls away from the chest wall.

3. Imaging/Labs Imaging is not always necessary, but can be in the right circumstances:

• If mass, skin changes, bloody nipple discharge → mammography with or without ultrasound.

• If no suspicious findings, may not necessarily need imaging, but will depend on presentation as well as if they are due for annual screening anyway.

• Chance of having breast cancer with no abnormality on physical exam or imaging is about 0.5%. 

How do you treat mastalgia? 

• Reassurance

  • Many times, women just want to know that their breast pain is normal and that they do not have breast cancer!

  • Studies have demonstrated this will be enough to satisfy 78-85% of women with normal findings.

  • Approximately 15% of women will need some other kind of treatment.

• First line therapies

  • Physical support - well-fitting bra for support, warm compress or ice packs or gentle massage.

  • Over the counter analgesics - Tylenol, NSAIDs; topical NSAIds may also be useful.

  • Change in or cessation of hormonal medications 

• Second line - if still having debilitating breast pain after first line treatments:

  • Tamoxifen - 10 or 20 mg daily, but can be associated with vasomotor symptoms of menopause.

  • Danazol - only FDA-approved treatment for mastalgia (fibrocystic breast disease) - usually around 200 mg daily.

    • Can be androgenizing, so avoid if planning pregnancy.

    • Rare hepatotoxicity with large doses (>400mg).

• Other therapies not proven by randomized trial data:

  • Lifestyle changes (weight loss, stopping caffeine, low fat diet - 15% fat).

  • Evening primrose oil.

  • Vitamin E.

    • Many of these are offered and available over the counter, and have not demonstrated evidence of harm, either! So they may still be useful in your anti-mastalgia arsenal.

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. 

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ACOG PB 224

Perinatal Depression

Depression is a major health disorder affecting around 10% of women, particularly in the perinatal and postpartum periods. Depression is twice as common in women as in men, and OB/GYNs should be familiar with its diagnosis and management, particularly in the perinatal period. You can read more with ACOG CO 757.

There are many different types of depression diagnoses, including: major depressive disorder, persistent depressive disorder, seasonal affective disorder, perinatal (postpartum) depression, premenstrual dysphoric disorder (PMDD), etc. According to the DSM-V, a major depressive episode is diagnosed when one has: 

• Five (or more) of the following symptoms have been present for a 2-week period and represent a change from previous functioning; at least one of the symptoms is either depressed mood or loss of interest/pleasure. 

• Symptoms cannot be explained by medications or another medical illness (i.e., hypothyroidism).

• The remaining (need 4+ from this list):

  • Depressed most of the day, nearly every day as indicated by subjective report or observation made by others;

  • Diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day;

  • Significant weight loss when not dieting or weight gain, or increase/decrease in appetite nearly every day;

  • Insomnia or hypersomnia;

  • Psychomotor agitation or retardation; 

  • Fatigue or loss of energy;

  • Feelings of worthlessness or inappropriate guilt;

  • Decreased ability to think/concentrate;

  • Recurrent thoughts of death/suicidal ideation.

Perinatal depression is defined separately as major and minor depressive episodes that occur during pregnancy or in the first 12 months after delivery. This is one of the most common medical complications during pregnancy and the postpartum period, affecting 1/7 women. 

Depression and other mood disorders can have devastating effects on women and their families: maternal suicide exceeds hemorrhage and hypertensive disorders as a cause of maternal mortality 

SO how do we screen for perinatal depression? ACOG recommends that obstetric care providers screen patients at least once during the perinatal period for depression and anxiety symptoms using a standardized tool, and again in the postpartum period during a comprehensive postpartum visit. There is evidence that screening alone can have clinical benefits for patients suffering with depression.

One of the most commonly used is the Edinburgh Postnatal Depression Screen, which is a 10 item survey that takes less than 5 minutes to complete. The sensitivity is estimated between: 59-100%, and specificity: 49-100%. A Spanish version is available.

The Patient Health Questionnaire 9 (PHQ-9) is another acceptable tool. Other items like the Postpartum Depression Screening Scale (PDSS) is more sensitive (91-94%) and specific (72-98%), but it is a 35 item survey and thus more time intensive.

Management of perinatal depression is a team sport, requiring multiple additional support members and medical team members. Medication prescription will vary for OB/GYNs and their comfort with this. In brief:

• Women with current depression/anxiety or a history of perinatal mood disorder should have close monitoring, evaluation, and assessment.

• Some OB/GYNs are comfortable starting antidepressant medication and following their patients, most commonly an SSRI. Psychiatry referral is also acceptable.

• Referral to social work and behavioral health - possibly for psychotherapy, which alone is a reasonable alternative to antidepressants if needed.

• For those with severe postpartum depression, another possibility is brexanolone.

  • Limited clinical experience and restricted availability 

  • Usually restricted to patients who do not improve with antidepressants 

Thyroid Disease in Pregnancy

The thyroid is obviously an important endocrine organ. As we’ve talked through many of our GYN episodes, from infertility to bleeding, the thyroid is part of our basic workup. Thyroid function is important in pregnancy as well, as uncontrolled thyroid disease is associated with adverse pregnancy outcomes. Subclinical thyroid disease, on the other hand, has unclear benefit and likely risks to therapy. Read and listen on, and check out ACOG PB 148 for further reading!

Thyroid physiology in pregnancy

• Thyroid function fluctuates in pregnancy in part due to bHCG

  • Thyroid stimulating hormone (TSH) and bHCG share an alpha subunit as hormones of the anterior pituitary. Thus, bHCG has mild thyrotropic effects.

    • In the first trimester, TSH may be lower as a reflection of this.

    • Free T4 may also be slightly elevated in the first trimester.

  • TSH values should revert to normal after 12 weeks gestation.

  • Important: TSH should not routinely be measured in women with hyperemesis gravidarum, unless other symptoms of hyperthyroidism are pregnant, for this reason. Treatment of transient hyperthyroidism associated with HG has not been shown to be beneficial. 

• Maternal T4 is transmitted transplacentally throughout the pregnancy and is important for normal fetal brain development

  • It is especially important before fetal thyroid gland begins functioning at approximately 12 weeks.

  • Thus, preconception screening and treatment for symptomatic thyroid disease is very important! 

• Nonpregnant iodine intake recommendation is 150 mcg daily.

  • 220 mcg daily in pregnancy.

  • 290 mcg daily in lactation.

    • Iodine is not always included in prenatal vitamins

    • American diet generally has enough iodine intake without supplementation, though should be a consideration for anyone with hypothyroid symptoms.

Thyroid Disease Testing

Recommendation by ACOG, Endocrine Society, Association of Clinical Endocrinologists recommend against universal screening for thyroid disease in pregnancy.

• Only screen women for those at increased risk of overt hypothyroidism, or with symptoms of overt hyper- or hypothyroidism. 

TSH and free T4 are the recommended baseline screening tests. 

• TSH is most important baseline screening test. In pregnancy, values:

  • 1st trimester: 0.1 - 2.5 mIU/L

  • 2nd trimester: 0.2 - 3.0 mIU/L

  • 3rd trimester: 0.3 - 3.0 mIU/L

• Free T4 (thyroxine) contextualizes the TSH result, and is often sent as a reflex if TSH is abnormal.

• Free T3 is generally not useful.

  • Very rare to have an abnormally high T3 causing hyperthyroidism; can be obtained if suspicious based on symptoms, with low TSH and normal T4.

• Antithyroid antibodies rarely lead to changes in management, so no evidence to routinely test for these. 

Pathophysiology of Various Thyroid Conditions in Pregnancy

Overt Hyperthyroidism:

• Occurs in 0.2% of pregnancies, with Graves’ disease (anti-thyroid antibody stimulation) accounting for 95% of cases.

• Diagnosis: low TSH (often undetectable), high free T4, and symptoms

  • tremors, tachycardia, weight loss, heat intolerance, insomnia, goiters, palpitations, hypertension (“activating symptoms”).

• Risks of Disease:

  • Maternal: hypertension, preeclampsia, heart failure

  • Fetal/Neonatal: premature delivery (medically-indicated), growth restriction/low birth weight, stillbirth, hydrops, neonatal hypothyroidism or hyperthyroidism.

    • Maternal anti-thyroid antibodies can cross placenta and can stimulate or inhibit fetal thyroid. 

    • This risk is not necessarily mitigated in neonates of mothers who have had treatment for Graves’ with surgery or radioactive iodine treatment -- antibodies can persist and still cross placenta. 

    • Thioamide treatment helps to suppress antibody production in medically-treated patients. 

Subclinical Hyperthyroidism:

• 1.7% of pregnancies.

• Diagnosis: low TSH, with normal free T4. 

• Has not been associated with adverse pregnancy outcomes.

  • Due to potential for antithyroid medication to cross placenta and cause adverse fetal effects, treatment is not recommended. 

Overt Hypothyroidism:

• 0.2 - 1% of pregnancies.

•  Diagnosis: high TSH, decreased free T4, and symptoms:

  • Fatigue, constipation, cold intolerance, weight gain, dry skin, hair loss, prolonged relaxation of DTRs, edema.

  • Challenge -- these symptoms sound a lot like early pregnancy!

    • Goiter more likely in women with Hashimoto thyroiditis -- 

      • most common cause of hypothyroidism in pregnancy (glandular destruction by thyroid autoantibodies).

• Risks of Disease:

  • Maternal: preeclampsia

  • Fetal/Neonatal: SAB/pregnancy loss, preterm birth, placental abruption

    • Untreated hypothyroidism may predispose to impaired neuropsychological development in offspring.

      • This is due to low active thyroid hormone, though; it is extremely uncommon for maternal thyroid inhibitory antibodies to cross placenta and cause fetal hypothyroidism. 

    • Prevalence of fetal hypothyroidism in offspring of women with Hashimoto is only 1 in 180k neonates. 

Subclinical Hypothyroidism

• 2-5% of pregnancies.

• Diagnosis: high TSH, normal free T4; unlikely to progress to overt hypothyroidism in pregnancy in otherwise healthy women.

• Bottom line: not associated with adverse pregnancy/neonatal outcomes.

  • Controlled Antenatal Thyroid Screening Study 2012 RCT with follow up to age 3, and additional follow up in 2018 to age 9.5.

    • Antenatal screening of thyroid function at mean GA of 12w3d.

    • No difference in neurocognitive development of offspring at both age 3 and age 9.5.

    • Secondary analyses find no definitive association with preterm birth, placental abruption, NICU admission, preeclampsia, GDM. 

• Recommendation by ACOG, Endocrine Society, Association of Clinical Endocrinologists recommend against universal screening for thyroid disease in pregnancy for this reason.

  • Thus -- as stated before, only screen women for those at increased risk of overt hypothyroidism or with symptoms of overt hypothyroidism. 

Treating Overt Thyroid Conditions in Pregnancy

Hyperthyroidism

• Mainstay of therapy is thioamide medications, either propylthiouracil or methimazole.

• PTU inhibits thyroperoxidase, an essential enzyme in creation of free T4. Also partially inhibits conversion of T4 to T3.

  • Preferentially used in1st trimester -- less readily crosses the placenta than methimazole.

  • Major side effect of note is hepatotoxicity, affecting 0.1-0.2% of women on PTU. 

  • Thus the recommendation is to switch to methimazole in the second trimester. No indication for routine LFTs.

• Methimazole also inhibits thyroperoxidase. 

  • Preferentially used in 2nd trimester due to hepatotoxicity.

  • Avoided in 1st trimester due to rare risk of embryopathy, characterized by esophageal or choanal atresia as well as aplasia cutis (congenital absence of skin, usually on the scalp).

• Rare but important side effect of both drugs: leukopenia in up to 10% of pregnant women on these drugs, which does not usually require therapy cessation.

  • However, rarely progresses to agranulocytosis in less than 1%, and this mandates discontinuing the offending agent. 

  • If women develop flu-like symptoms, they should discontinue these meds and immediately obtain CBC to assess WBC count. 

• Initial dosing for both drugs is empiric:

  • 50-150mg TID for PTU

  • 10-40mg total daily divided into 2-3 doses for MTZ.

• Goal is to use the  lowest thioamide dose to maintain free T4 in the high-normal range, regardless of TSH level. 

  • Measure free T4 concentrations q2-4 weeks after initiating therapy (not TSH levels!) and adjust thioamide dose accordingly. 

Hypothyroidism

• Levothyroxine is the mainstay for thyroid hormone replacement. 

  • Dosing should begin at 1-2 mcg/kg daily, or approximately 100mcg daily. 

  • Monitor therapy by measuring TSH levels every 4-6 weeks (not T4!)

    • Adjust dose by 25-50 mcg increments until TSH normalizes.

    • Anticipatory 25% increase in T4 replacement at pregnancy confirmation in women with known thyroid disease may reduce the risk of significant hypothyroidism in early pregnancy in higher risk women (i.e., history of thyroidectomy or radioiodine ablation).

Thyroid Storm and Thyrotoxic Heart Failure

• Thyroid storm is rare - 1-2% of pregnant patients with hyperthyroidism.

  • Cardinal symptoms include fever, tachycardia, arrhythmias, and CNS dysfunction. Develops abruptly and leads to multiorgan failure. 

• Thyrotoxic heart failure is more common, actually, and has been identified in 8% of women with uncontrolled hyperthyroidism.

  • Due to an excess of free T4 and effects on myocardium.

  • Decompensation usually precipitated by other disease, such as PEC, sepsis, anemia. 

  • Fortunately this is often reversible with treatment.

• Tenets of treatment of these conditions:

  • Evaluate TSH and T4, but if suspected -- do not withhold treatment!

  • Follow the ACOG algorithm here (read out loud):

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ACOG PB 148

Postpartum Thyroiditis

• Defined as thyroid dysfunction within 12 months of delivery that can manifest as hyperthyroidism, hypothyroidism, or both. 

  • Transient autoimmune thyroiditis present in 5-10% of women in this time period.

  • Often attributed to “the stresses of motherhood” so actually infrequently encountered clinically. 

• Often develops in two phases:

  • First, hyperthyroid state that is charactrized by simultaneous thyroid gland destruction, lasting maybe a few months at the longest.

    • Often a small, painless goiter can be found in these patients.

    • If diagnosed during this phase, thioamides are generally ineffective, but beta blockers can help with symptoms if necessary. 

  • Then, hypothyroid symptoms that begin somewhere between 4-8 months postartum, requiring thyroid replacement for 6-12 momnths.

  • Most women will have symptoms resolve sponteneously, but up to ⅓ of women will develop permanent hypothyroidism. 

Thyroid nodules in pregnancy

• Can be found in 1-2 % of reproductive-aged women.

• If pregnant, should perform H&P, TSH, and ultrasound of the neck

  • Ultrasound reliably detects nodules greater than 0.5 cm.

  • If suspicious for malignancy, next step is fine needle aspiration.

    • Radioiodine scanning is not recommended in pregnancy due to theoretical risk of fetal irradiation. 

• If cancer is detected, multidisciplinary discussion should be had regarding treatment timing. 

  • Many times surgery is delayed until after delivery due to concern for potential removal of parathyroid glands. 

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:

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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.