Nephrolithiasis for the OB/GYN

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Background

  • Kidney stones are super common - affecting up to 10% of US adults.

    • There is a described “kidney stone belt” in the US where they are even more prevalent - mostly the South and Southeast of the US.

  • Presentation is frequently classic, but to review:

    • Unilateral flank pain, colicky in nature, waxing-waning with episodes every 20-60 minutes

    • Can radiate to groin

    • Urinary urgency, hematuria, or dysuria also present

    • Nausea, vomiting, and generalized abdominal pain may also be present 

      • Pain also will relieve itself once the stone passes - many patients familiar with the symptoms will recognize this.

  • Risk factors for stones include:

    • Hypertension

    • Gout

    • Obesity

    • Diabetes

    • Certain dietary characteristics:

      • Excessive protein, carbohydrate, and sodium intake

      • Poor fiber intake

      • High oxalate or consumption of carbonated drinks with phosphoric acid (mostly present in higher quantities in colas)

    • Recurrent UTIs with urease-producing organisms 

      • Most classically, Proteus mirabilis 

    • Certain medications and supplements: 

      • Topiramate, Furosemide, Acetazolamide

      • Vitamin C, Vitamin D

  • Kidney stones are made of different stone materials:

    • The most common is calcium oxalate, followed by calcium phosphate (>80%).

    • Other types are uric acid, struvite, and cystine stones.

Diagnosis and Evaluation of Nephrolithiasis

  • Labs

    • Patients with suspected stone should receive a BMP to assess kidney function

    • Should also have a UA to assess for hematuria and potential infection

      • Concomitant UTI may complicate stone management

  • Imaging

    • Preferred: CT abdomen/pelvis without contrast

      • This allows for good imaging of the kidneys and bladder

      • CT characteristics of stones can also help predict stone composition and guide therapy.

    • Pregnancy: ultrasound of kidneys and bladder

      • This avoids radiation while still providing good imaging to evaluate for presence of stones, and if severe obstruction is present.

      • Bladder follow through is important to evaluate for presence of “ureteral jets,” or visible efflux on ultrasound of urine entering the bladder from the ureters.

    • US is not a great modality - sensitivity of ultrasound for stone detection is only about 50-75%, whereas for CT it is 90%+. 

      • However, complication rates from missed diagnoses are similar between CT and ultrasound (less than 1%), and thus it’s prudent in the pregnant patient to use ultrasound if stones are the primary suspicion.

Basics of Management

  • Most patients can fortunately be managed expectantly with pain medication and hydration until the stone passes through. 

    • Hospitalization may be required if patients can’t take PO, or have uncontrolled pain or fever.

    • Patients should strain their urine for several days and bring any collected stones/gravel to clinic.

      • This will allow for stone analysis and to direct preventive therapy.

  • NSAIDs are preferred for pain management over opioids.

    • In pregnant patients, it can be considered to give a single dose of ketorolac if not near delivery timing to provide some short-term relief; however, they are one class of patient where opioids may be used instead.

  • Stone size is the best predictor of passage:

    • < 5 mm stones almost always pass spontaneously. 

    • Stones > 10mm are unlikely to pass spontaneously, as are stones that are in the proximal ureter.

  • Medical expulsive therapy can be considered with alpha blockers for stones between 5-10mm:

    • Tamsulosin 0.4mg daily for up to four weeks can help facilitate stone passage.

      • These generally have minimal side effects.

      • Most effective for more distal stones.

      • There is not much safety data for pregnancy, so typically are not used in pregnant patients.

    • Nifedipine and other calcium channel blockers can also be considered, but with lower success rates compared to alpha blockers.

Urology Referral / Complex Management

  • Surgical indications include persistent pain, infection, and urinary tract obstruction.

    • Urgent decompression is required in patients with:

      • Suspected/confirmed UTI

      • Bilateral obstruction and AKI

      • Unilateral obstruction and AKI in patients with solitary kidney

    • Elective decompression can be considered in patients with:

      • Stones > 10mm

      • Stones under 10mm that have not passed after 4-6 weeks of observation

      • Pregnant patients with stones after failing observation period

      • Persistent kidney obstruction

      • Recurrent UTI

  • Surgical approaches can be with shockwave lithotripsy, ureteroscopy with stenting, or percutaneous nephrolithotomy.

    • Stenting and shockwave therapy are generally preferred, and urologists will choose based on stone location and characteristics.

    • Shockwave therapy cannot be performed with an indication for urgent decompression, nor in the pregnant patient.

      • Ureteroscopy with stenting is the preferred method in pregnancy.

      • Stent exchange or nephrostomy tube change has to be performed much more frequently in pregnancy (every 4-6 weeks) due to higher GFR and thus higher risk of stent/tube obstruction and/or infection. 

Prevention of Recurrent Stones

  • Fluid intake is very important:

    • Drink enough to produce at least 2L of urine a day. Spread fluid throughout the day. Studies have shown even small amounts of urine volume increase reduces recurrence!

    • Water is the best choice, but avoid sweetened soda at the very least due to phosphoric acid content.

  • Limit sodium intake to under 2300mg / day

    • This is due to calcium reabsorption becoming more favorable in the proximal tubule down the same sodium concentration gradient.

    • By reducing dietary sodium, you enhance reabsorption of sodium (and consequently calcium).

  • Fruits and vegetables rich in potassium help excrete citrate better, limiting stone formation.

  • Weight loss in obese patients may also help prevent stone recurrence, though data is limited.

  • In patients with the most common type of stone (calcium oxalate):

    • A calcium-rich diet may be helpful, while trying to obtain as much from dietary sources as possible.

      • Restricting calcium intake is not advised unless it is excessive at baseline.

    • Reduce animal protein intake

      • High sulfur content in animal proteins generates more acid, which then through a variety of complicated renal mechanisms may increase calcium excretion and stone formation.

    • Limit intake of oxalate, fructose, and sucrose.

      • These all increase calcium excretion and/or oxalate excretion.

Primary Ovarian Insufficiency

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Reading: Committee Opinion 604

What is Primary Ovarian Insufficiency? 

  1. Definition 

    1. Depletion or dysfunction of ovarian follicles with cessation of menses before age 40 

    2. Used to be caused premature menopause or primary ovarian failure 

    3. Note: should not be confused with menopause because 5-10% of women with POI can still experience spontaneous conception and delivery 

What Causes POI? 

  1. Causes of POI 

    1. There are many, but usually caused by chromosomal abnormalities or damage from chemotherapy or radiation therapy  

    2. Common cause: chemo and radiation 

      1. Immediate loss of ovarian function after chemo/radiation is called acute ovarian failure 

      2. Highest incidence occurs after use of alkylating agents or procarbazine 

      3. Younger the patient at time of receiving chemo, the more likely some follicles will survive  

    3. Common cause: premutation of the FMR1 gene for fragile X 

      1. As a reminder, Fragile X is an X-linked dominant condition

      2. Caused by an increase in the repeats of CGG, typically >200 

      3. In fragile X, there is genetic anticipation, meaning that the number of repeats can increase as they get passed onto future generations 

      4. A pre-mutation is when there is between 55-200 repeats, and those with Fragile X or a pre-mutation have a 20% chance of developing POI in their lifetime 

      5. 1% of pre mutation carriers will experience final menses before age 18 

    4. Another common cause: Turner Syndrome 

      1. Chromosomal abnormality with XO instead of XX 

      2. Certain people can also have Turner mosaicism, which can also lead to POI 

      3. When evaluating adolescents with primary amenorrhea and no associated comorbidities, about 50% will have chromosomal abnormalities 

      4. Can also lead to pubertal and growth delays 

    5. Gonadal dysgenesis 

    6. Less frequently can be caused by infection or infiltrative process 

    7. Other cause could be iatrogenic (ie. removal of the ovaries) 

    8. Can also have autoimmune component, as 4% of patients with POI will have adrenal or ovarian antibodies 


How do we diagnose primary ovarian insufficiency? 

  1. Diagnosis 

    1. Unfortunately, no consensus criteria to identify POI in adolescents, and so a delay in diagnosis is common 

    2. Some adolescents may have hot flashes or vaginal dryness, but the most common presenting symptom is POI 

    3. So in someone who is presenting with amenorrhea or menstrual irregularity for 3 or more months, important to evaluate for all etiologies (ie. pregnancy, PCOS, hypothalamic amenorrhea, thyroid abnormalities, hyperprolactinemia, and POI) 

  2. Work up 

    1. History and physical 

      1. Ask about menstrual history, family history of early menopause, and other factors that may place patients at risk for POI (ie. above etiologies) 

      2. Physical exam should include other signs of disorders of sexual development (ie. breast development, uterus present or absent) 

    2. Labwork 

      1. Obtain basal FSH and estradiol levels - do not obtain when patient is on OCPs or other hormonal medications 

      2. Pregnancy test 

      3. Thyroid function tests and prolactin 

    3. If gonadotropins are elevated in menopausal range (FSH 30-40 mIU/L), a repeat FSH measure is indicated in 1 month

      1. If FSH is still elevated, this is diagnosed as POI 

      2. Hypoestrogenism is when estradiol levels are <50 pg/mL 

      3. Once diagnosis is established 

        1. Karyotype 

        2. FMR1 pre mutation testing 

        3. Adrenal antibodies 

        4. Pelvic ultrasound  

        5. Meeting with genetic counselor depending on genetic findings 

    4. Other tests being studied  

      1. AMH is currently being used to assess ovarian reserve, but should not be used to determine if someone is fertile or not 

      2. Inhibin B is not recommended as there is significant variability between menstrual cycles 


Management 

  1. Note about treatment 

    1. Diagnosis can be emotionally distressing in young women 

    2. Therefore, treatment should have focus on sensitivity to both physical and emotional needs 

    3. Some patients may need referral to counseling/group therapy for support  

  2. Goal overall physically is to replace the hormones that the ovary would be producing before age of menopause 

    1. May need more than menopausal women 

    2. Pubertal development 

      1. Breast development 

        1. Initiate estrogen and increase gradually before administering progesterone until breast development is complete to prevent tubular breast formation 

      2. Consultation to REI or PAGs for further management 

    3. Ongoing hormonal treatment 

      1. Will be necessary to prevent comorbidities 

      2. Usually, transdermal, oral, or occasionally transvaginal estradiol of doses of 100 mcg daily is the therapy of choice 

        1. Remember that oral estradiol can be used, but there is a higher risk of VTE compared to transdermal estrogen 

      3. Addition of progesterone for 10-12 days each month is protective against endometrial hyperplasia 

      4. The instinct may be to reach for OCPs, but OCPs have a much higher dosage of estrogen than is needed, and so is not first line treatment 

  3. Associated Comorbidities 

    1. Bone loss 

      1. We know that ovarian function loss can affect bone architecture, especially in adolescents when bone accrual is at its maximum 

      2. There is no consensus regarding DEXA scan or monitoring bone density annually; some do, but the the implications of low bone mineral density result in this population is unclear given low risk of fracture 

      3. Long term use of bisphophonates is not recommended because of uncertain adverse effects and safety profiles 

    2. Cardiovascular Disease 

      1. Those with early estrogen loss are at higher risk of CV mortality 

      2. Other than supplementing estrogen, there should be monitoring 

      3. Routine visits should also focus on other methods of prevent CV morbidity: smoking avoidance, appropriate diet and exercise 

      4. Blood pressure measurement annually and lipid levels every 5 years 

    3. Endocrine Disorders 

      1. 20% of adults with idiopathic POI will experience hypothyroidism, commonly Hashimoto’s thyroiditis 

      2. No formal recommendation, but appropriate to test for thyroid insufficiency every 1-2 years 

      3. Test for adrenal antibodies and should undergo yearly corticotropin stimulation testing as there is a 50% chance of developing adrenal insufficiency 

  4. Fertility and Contraception 

    1. For patients that desire to start families, they should be referred to REI to discuss options 

      1. Can have egg preservation if possible 

      2. Can also discuss other ways of having offspring (ie. donor eggs, gestation carrier) 

    2. Fertility can still persist as long as few follicles are present 

      1. Therefore, contraception should still be a discussion 

      2. OCPs can be prescribed, but other methods such as IUDs or barrier methods can also be used 

      3. Even if estrogen method is not chosen, estrogen should still be supplemented for the above reasons 

      4. A missed period should still warrant a pregnancy test 

Amniotic Fluid Embolism

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Read along: SMFM Clinical Guideline 9: AFE: diagnosis and management 

AFE: Background/Presentation

  • AFE is a clinical diagnosis characterized by a triad of sudden onset symptoms:

    • Sudden hypoxia 

    • Hypotension, often resulting in cardiac arrest / cardiovascular collapse

    • Followed by coagulopathy in 83% of cases

      • Coagulopathy may be in conjunction with cardiopulmonary symptoms, or follow them.

      • Often profound with bleeding from venipuncture or surgical sites, hematuria, GI hemorrhage, vaginal bleeding, epistaxis. 

  • Importantly, the diagnosis is clinical. Based on this triad and exclusion of other potential causes.

    • Cases are often dramatic - preceded not infrequently by impending sense of doom from patient, change in mental status, agitation.

      • Fetal status may also change with sudden profound decelerations, loss of variability, and terminal bradycardia.

    • No lab test can confirm or refute the diagnosis.

  • A national registry reports with respect to case timing:

    • 70% occur during labor

    • 11% after vaginal delivery

    • 19% during cesarean delivery

  • Incidence is hard to know given its rarity - likewise, predicting AFE is also impossible - there are no defined and true risk factors.

    • There is some potential relation related to moments where, “exchange of fluids between fetal and maternal compartments is more likely,” such as operative or cesarean delivery, placenta previa, placenta accreta, abruption

What causes AFE? What's the pathophysiology? 

  • It’s unclear what exactly causes AFE, but again, it’s often reported at the time of some disruption of maternal-fetal interface. 

    • Whether amniotic fluid passing into maternal circulation is the underlying cause or not, there are a fair number of subsequent clinical manifestations that can be observed.

  • First, there is massive pulmonary vasoconstriction and possible mechanical obstruction of pulmonary vasculature due to amniotic fluid components.

    • This vasoconstriction results in acute cor pulmonale - or sudden right ventricular failure.

    • Accompanying this is acute respiratory failure and severe hypoxemia.

      • The best way to think about these coming together (and potentially a valid way to think pathophysiologically too) is a massive, anaphylactoid reaction. 

    • With the massive afterload on the RV, on echocardiogram you can see a dilated RV with ballooning of the ventricular septum towards the left.

      • TTE and/or TEE during an event may help to visualize this concern in AFE.

  • Cor pulmonale in this acute fashion leads then to left-ventricular failure - there’s no blood going forward to the LV! - which results in profound systemic hypotension. 

  • Finally, it is thought that the amniotic fluid or inflammatory insult activates factor VII in the coagulation cascade → thus activating platelets and consuming them in a process that ultimately results in DIC.

    • The hemorrhage that results further exacerbates the hemodynamic instability at the level of the heart, and multiorgan failure can result.

SMFM Clinical series: afe


How should AFE be managed?

  • First, suspicion: AFE should be considered in the differential for any sudden cardiopulmonary collapse in pregnant or recently postpartum patients.

  • Next, high quality CPR: BLS/ACLS. 

    • Management does not differ initially with cardiac arrest due to any other cause, so the most important thing you can do is to be BLS and ACLS-certified. 

    • Chest compressions should be initiated immediately - take a listen back to our maternal cardiac arrest episode for a refresher on CPR. Recall the major points, though:

      • Same rate of compressions as for non-pregnant individuals (100/min), aiming for compression depth of 2 inches.

      • Switch compressors every 2 minutes to prevent fatigue.

      • If undelivered, tilt to left lateral decubitus or displace the uterus leftward to prevent aortocaval compression.

      • Resuscitative hysterotomy (aka perimortem cesarean) at 4 minutes without ROSC if not imminently delivering vaginally. 

    • And important to a high-quality ACLS resuscitation is having a diverse team - anesthesia, RT, critical care, OB/MFM, nursing, blood bank, and pediatrics should all be part of the care and emergency response!

  • There are no well-studied medication protocols to treat AFE, and none are discussed in the SMFM Clinical Guidelines.

    • The most discussed one in many circles is the “A-OK” protocol, which consists of:

      • Atropine 1mg - reversing parasympathetic activity that may contribute to pulmonary vasospasm

      • Ondansetron 8mg - blocks serotonin receptors that may be found in vagal terminals of heart and lungs, and would in turn contribute to pulmonary vasoconstriction 

      • Ketorolac 30mg - blocks thromboxane, which is a major platelet activator

        • The idea behind this therapy is to potentially interrupt these vasoconstricting/inflammatory pathways felt to contribute to AFE; however, this is obviously very difficult to study in a systematic or rigorous way.

  • Post-arrest care is also extremely important.

    • MAP goal of 65 mmHg.

    • Appropriate oxygenation with attempt to wean oxygen to minimal possible to avoid ischemia-reperfusion injury. 

    • Laboratories: essentially, draw the rainbow to be broad. 

      • But checking in on CBC, CMP, troponins, BNP, and coag profile (fibrinogen, PT/aPTT) are good places to start.

    • If not already initiated, preparation for massive transfusion with ongoing/impending coagulopathy.

      • TXA can be considered.

      • Treating atony remains important - the uterus may become atonic in the context of profound hypotension/arrest.

        • One major challenge as a surgeon is to see the bleeding and atony, and be tempted into performing a hysterectomy. Don’t be tempted! 

          • It may very well serve you in the setting of an AFE not to perform a hysterectomy, as further incisions may give further sites of bleeding that are difficult to control. Wait for the products to get on board and resuscitation to catch up.

      • Transfusion using best practice of 1:1:1 ratio (RBC:plasma:platelet).

    • Managing airway concerns and right ventricular failure, if present on echo

      • There are a variety of agents that can be used RV failure, including sildenafil, pressors such as dobumtamine or norepi, and inhaled nitric oxide or prostacyclins.

      • ECMO can also be considered

        • Admittedly, these will be in the purview of our anesthesia/critical care colleagues so we won’t focus much more on them! 

  • In your hospital, verify if you have a protocol or checklist to help with AFE management.

Pessaries for the GYN Patient, feat. Dr. Edward Kim

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What are pessaries?

  • Pelvic organ prolapse (or POP) and stress urinary incontinence (or SUI) are common problems that impact millions of women in the world.

  • A pessary is a support device placed vaginally that can be used to treat symptoms of POP, SUI, or both.

    • Pessaries are generally cost effective, well-tolerated, safe and can help avoid surgery.

      • For POP, up to 90% of patients report relief of symptoms like pressure and bulge.

      • For SUI, about half of patients report improvement in urinary symptoms.

History of the pessary

  • Historically, the first use of pessary for reduction of pelvic organ prolapse was described by Hippocrates.

    • He put a halved pomegranate soaked in wine into the vagina.

  • In 1860, Dr. Hugh Lenox Hodge, an ob/gyn faculty at the University of Pennsylvania, used newly developed vulcanized rubber to create a pessary shaped more anatomically.

    • Today, most pessaries are made of soft, flexible silicone thus considered non-allergenic.

The Modern Pessary

  • The most commonly used pessaries are ring, Gellhorn and donut. 

    • Ring pessary is a go-to in practice.

      • Subtypes: Ring without support

      • Ring with support (kinda looks like a mini frisbee),
        Ring without support with a knob

      • Ring with support with a knob.

        • The knob sits under the pubic bone and helps with stress urinary incontinence. So a ring with support and a knob will address POP and SUI. Rings can be removed by patients fairly easily.

    • A Gellhorn has a stem and a concave disc (kinda looks like a baby pacifier).

      • The concave disc part sits below the vaginal apex and creates somewhat of a suction.

      • The stem sits posteriorly and prevents the pessary from flipping around.

        • Gellhorns are little more difficult to place. Patients seldom can remove them on their own.

        • For removal, a provider usually needs to grasp the stem with their fingers or a ring forceps, gently wiggle it out to break the suction allowing for removal.

        • Gellhorns are generally used for more severe prolapse.

    • A donut (as the name implies) looks like a mini donut and it achieves its function by occupying the vagina.

      • A donut works better for more severe prolapse, as well, and difficult for patients to remove on their own.

Indication and counseling:

  • Patients with symptomatic POP or SUI who desire to avoid surgery, poor candidate for surgery, desire further childbearing, current pregnancy or within 12 months postpartum.

  • Contraindications include:

    • active pelvic infection,

    • latex allergy (as some inflatable pessary are composed of latex),

    • non adherence to care and follow up

  • Studies report a very wide range of patient acceptance of pessary: from 42 to 100%.

    • Patients who decline tend to be younger, sexually active,  nulliparous, or have severe POP or SUI and desire surgical correction.

    • But it also depends on the counseling. In our practice, we discuss pessary in the range of management options for POP and SUI. We sometimes use it as a bridge between now and surgery for patients who prefer symptom relief now.

Placement:

  • Placement comes with practice and it often involves trial and error.

  • There have been no identified reliable predictors of which size pessary should be tried first.

  • Start with a ring with support pessary (ring with support and a knob if also trying to address SUI).

  • Identifying the starting size (say, 3, 4, 5) comes with practice and pelvic exam. Wet it with warm water first.

    • You could use lubricant but if you use too much it may be too slippery for you to handle and also easier for it to be expelled.

  • Fold it in half like a taco, insert, and allow it to resume its disc shape in situ. Remember, it should NOT be painful. If the patient says it’s painful once it’s placed, then it is often too big.

    • Liken it to a corrective device like glasses or contact lens. When you first start using it, you notice that it’s there. But it should not be painful and with time you often forget it’s there.

  • Then have pt Valsalva.

    • It’s okay that you can see the pessary descend as long as it does not completely get expelled.

  • Then have them ambulate and go to the toilet and Valsalva with a toilet hat to catch the pessary if it does get expelled.

    • If it’s still in situ after that and patient has no discomfort, we send them home with it.

  • Placement of Gellhorn, donuts, and other types of pessaries are little different and may be best reserved for providers who have more experience with them. But I think ring pessaries can be something everyone can have in their toolbox.

Maintenance:

  • Patients who wish to and have the dexterity to maintain the pessaries on their own are instructed to take it out and clean with warm soapy water as often as they want but usually at least once a week.

    • If they are unable to, then typically they come to the clinic every 3-4 months for maintenance.

  • Patients with Gellhorn, donut, or other types of pessaries that patients cannot remove easily on their own also follow up every 3-4 months. At these visits, the pessary is removed, gently cleaned, and a speculum exam is done to assess for any excoriation or abrasion.

  • For postmenopausal patients without contraindication for topical vaginal estrogen, we typically have them use it to prevent significant vaginal excoriation or abrasion since atrophy can worsen these.

Complications:

  • Most common complaints are increase or change in vaginal discharge or odor. Reassurance and ruling out for vaginitis and bacterial vaginosis are reasonable next steps. Reports of vaginal bleeding long after placement warrants exam in the office.

  • Spontaneous expulsion or difficulty with voiding or defecation or pain often means a different size or shape should be tried.

  • Pessaries that have been left in situ and neglected for prolonged period of time should be taken seriously. Embedded pessaries may need removal under general anesthesia.

  • But overall, it is generally very safe.

Premenstrual Dysphoric Disorder (PMDD)

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Great Pearls of Exxcellence article about this from Society for Academic Specialists in General Ob/Gyn (SASGOG).If you haven’t heard of the Pearls of Exxcellence, go and check it out! Great review for CREOGs and boards.

Background

  • What is PMDD? 

    • You have probably heard of premenstrual syndrome (PMS) 

      • PMS: wide variety of signs and symptoms that occur in a predictable pattern usually before or during menses 

        • Symptoms/signs: mood swings, tender breasts, food cravings, fatigue, irritability, depression 

        • Can affect up to 3 out of 4 menstruating people 

        • Estimated that 15-20% of patients who have PMS will have PMS that significantly impairs functioning 

    • PMDD is a more severe form of premenstrual syndrome, according to the DSM-V 

      • Usually appears the week before menstruation and end within a few days of menses starting 

      • Will involve at least one severe affective symptom such as depression, hopelessness, anxiety, affective lability, or persistent anger that resolves around time of menses onset 

      • But not just mood, it can involve multiple systems (don’t have to list all of them, just some) 

        • Psychological symptoms 

          • Irritability, nervousness, feeling of lack of control, anger, insomnia, difficulty concentrating, severe fatigue, depression, anxiety, confusion, forgetfulness, paranoia, emotional sensitivity

        • Respiratory problems 

          • Allergies, infections 

        • Eye problems 

          • Vision changes 

        • GI symptoms 

          • Abdominal cramping, bloating, constipation, nausea/vomiting, pelvic heaviness or pressure, backache 

        • Skin symptoms 

          • Acne, itching, aggravation of other skin disorders (ie. coldsores) 

        • Neurologic/vascular symptoms 

          • Headache, dizziness, fainting, numbness, tingling, heart palpitations, muscle spasms 

        • Other 

          • Painful menstruation, diminished sex drive, appetite changes, food cravings, hot flashes, weight gain/swelling, breast tenderness/pain 

      • Approximately 3-8% of patients who menstruate will have PMDD 

  • Differential diagnosis 

    • Diagnosis of PMDD 

      • As discussed above, can be any of those symptoms + one severe affective symptom 

      • Be coordinated with timing of menses (onset prior to menses and resolves within a few days of menses) 

      • Demonstrates a history of two consecutive menstrual cycles in exclusion of other medical conditions 

    • Should rule out primary mood or anxiety disorders, thyroid function, substance abuse, and menopausal transition

      • This means that we need to take an extensive history and do a physical exam to rule out these other possibilities 

      • Other tests that you may want to order depend on patient symptoms 

        • Ie. excessive fatigue/insomnia/temperature dysregulation, weight gain, etc: rule out thyroid disorders 

        • If concerns for premenopausal transition, can order FSH/estrogen

        • If concerns for heavy bleeding, irregular bleeding, depending on situation may need to do endometrial biopsy, etc

        • We won’t go into everything here, as we have other episodes that discuss how to manage AUB 

        • If you think the patient has a mood disorder that is not due to menstrual cycle, can be a reason to start treatment, refer to psychiatry/psychology 

What are some conservative ways to manage PMDD? 

  • A word on management 

    • As with many chronic conditions in medicine, the goal of treatment is to improve patient function and symptoms, with the understanding that we may not be able to make symptoms go away 100% 

    • Often, it may not be a single management method that helps but a combination 

  • Lifestyle modifications 

    • Diet 

      • Some evidence that diet can affect severity of PMS and PMDD - doesn’t mean that eating certain foods will cause PMDD, but there is a possibility that certain dietary modifications can reduce severity 

      • Reduction of sugar, salt, red meat, caffeine, and alcohol may reduce PMDD symptoms 

      • Some evidence that calcium and vitamin B6 supplementation can benefit 

    • Exercise 

      • Aerobic exercise can improve PMDD symptoms 

      • One study showed that women that did 60 minute aerobic exercise 3x/week for 8 weeks felt much improved physically, mentally, and emotionally 

      • A systematic review and meta-analysis shows that there is likely some improvement in symptoms, but some uncertainty remains: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465566/

    • Adjunct/alternative treatments 

      • Some studies, but no enough evidence at this time to recommend routinely the following: 

        • Massage, biofeedback, yoga, chiropractic manipulation, evening primrose oil and Chinese herbal medicines 

        • If patients find these work for them, they can continue 

      • Things that have some limited evidence that they may work: bright light therapy, stress reduction, and adequate sleep 

      • Low quality evidence suggests that acupuncture may reduce symptoms of PMDD 

  • Cognitive behavioral therapy

    • Can be effective 

    • Group psychoeducation and relaxation therapy may benefit patients with significant stress or anxiety component 

  • Pharmacologic Therapy/Medication 

    • Psychoactive therapy 

      • Selective serotonin reuptake inhibitors (SSRIs) have been shown to be very effective and are first line treatment for PMDD 

      • Results in response in 60-70% of patients 

      • You can try both continuous or just luteal phase SSRIs 

      • No single agent has been shown to be better than the other 

      • First line therapy include sertraline, paroxetine, citalopram, escitalopram, and fluoxetine 

      • Second line: venlafaxine, alprazolam 

    • Hormonal therapies 

      • Combined oral contraceptives have shown mixed effects in RCTs 

        • Both cyclic and extended regimens inhibit ovulation and may reduce physical symptoms 

      • For patients who desire contraception, COC is reasonable first line therapy with addition of SSRI if needed 

      • Drospirenone-containing COC formulations are specifically FDA approved for treating PMDD, with 48-60% of patients reporting significant improvement 

    • NSAIDs 

      • May be useful to manage physical symptoms 

More advanced therapies 

  • GnRH agonists 

    • Example: leuprolide 

    • Has been shown to be effective for ovulation suppression and physical symptoms of PMDD 

    • Long term use should be approached with caution, and only after informed consent 

    • Reasoning: side effects (ie. hot flashes), and irreversible bone loss 

  • Surgery 

    • If patient has disabling symptoms refractory to other medical therapies, oophorectomy can be considered 

    • A 3-6 month trial of GnRH agonist demonstrating efficacy is a prerequisite to surgical treatment 

    • Must discuss risks and benefits, given oophorectomy in younger women can be associated with multiple morbidities such as cardiovascular events and osteoporosis