CMS250 - Wk 5, Dysmenorrhea

• Dysmenorrhea is pelvic pain with menses, often described as cramping.

Primary Dysmenorrhea

• It is menstrual pain with no identifiable pelvic pathology.

Secondary Dysmenorrhea

• It refers to menstrual pain associated with an identifiable pelvic pathologic condition.
• Endometriosis and ovarian cysts are examples.

Membranous Dysmenorrhea

• It is intense cramping pelvic pain associated with the spontaneous sloughing of the endometrium.
• The endometrium comes off in one piece that retains the shape of the uterine cavity.
• It is rare.

Epidemiology of Dysmenorrhea

• 16-91% of women experience dysmenorrhea.
• 2-29% of women experience severe pain.
• Primary dysmenorrhea typically peaks in adolescent and early 20s females, with 20-90% of adolescents affected.
• The prevalence of primary dysmenorrhea decreases with age and parity.
• Secondary dysmenorrhea typically peaks in females in their 40s-50s and is suspected in females over 25 with new onset pain.
• The prevalence of secondary dysmenorrhea is attributed to individual conditions.

Risk Factors

• Risk factors include age, longer/heavier menstrual flow, nulliparity, and family history.
• Modifiable risk factors include smoking and attempts to lose weight independent of BMI, and high waist-to-hip ratio (WHR).
• Mental health conditions such as depression/anxiety, disruption of social networks, and sexual abuse also increase the risk.
• Regular exercise, OCP use, early childbirth, and fish intake are protective.
• Heavy menstrual flow has an odds ratio (OR) of 4.7.
• Premenstrual symptoms have an OR of 2.4.
• Age younger than 30 years has an OR of 1.9.
• Clinically suspected PID has an OR of 1.6.
• Sexual abuse has an OR of 1.6.
• Menarche before age 12 has an OR of 1.5.
• Low BMI (less than 18.5 kg/m^2) has an OR of 1.4.
• Sterilization (tubal) has an OR of 1.4.

Primary Dysmenorrhea

• It is menstrual pain in the absence of organic pathology, often beginning 6-12 months after menarche.
• It involves recurrent, crampy, suprapubic pain prior to or during menses, lasting 2-3 days.
• Pain may radiate to the back or legs and be associated with nausea, fatigue, bloating, and general malaise.
• A normal pelvic exam results.
• Urine tests rule out pregnancy (hCG) and infection (STIs).
• Management is empiric, involving non-pharmacologic methods or NSAIDs, and may be co-managed with a GP.
• Prognosis: tends to improve with age with no known long-term consequences.

Etiology

• There are many theories to explain the cause of primary dysmenorrhea.
• The biological cause has the strongest evidence over psychological and anatomical causes.
• Abnormal and increased prostanoid secretion leads to abnormal uterine contractions, reducing uterine blood flow and causing uterine hypoxia.
• A drop in progesterone causes the endometrial lining to slough.
• Prostaglandin F released by endometrial cells causes contractions, with contraction intensity proportional to prostaglandins released.
• Increased leukotriene levels may be a contributing factor.
• Vasopressin may cause increased uterine contractility, leading to vasoconstriction and ischemic pain.

Physical Exam and Lab Testing

• A physical exam of the abdomen and pelvis is important to identify potential causes of secondary dysmenorrhea.
• No lab tests are required or helpful in diagnosing primary dysmenorrhea, but they do aid in the diagnosis of some secondary causes.
• Diagnostic imaging is unlikely to be helpful without abnormal findings on physical examination.
• Further investigation is indicated if:
  • Physical exam findings suggest a secondary cause, such as a pelvic mass or uterine outflow obstruction.
  • The patient is refractory to first-line agents like NSAIDs or OCP/CHCs.
  • An adequate physical examination is not possible due to significant obesity or patient refusal.

Pelvic Examination

• A pelvic examination should be performed in adolescents with a history of vaginal intercourse because of the high risk of PID in this population.
• For patients who have never been sexually active, an abdominal exam and inspection of the external genitalia are sufficient.
• It should be performed if endometriosis or other secondary causes are suspected in females of any age.

Findings During A Pelvic Exam

• For endometriosis (pelvic exam):
  • Sensitivity is 76%
  • LR + is 2.92
  • LR - is 0.32
• Endometriosis can cause a fixed uterus or reduced uterine mobility, adnexal masses, and uterosacral nodularity.
• Adenomyosis can cause uterine enlargement or asymmetry.
• PID can cause mucopurulent cervical discharge.

Diagnosis

• Obtain a thorough history to determine the severity, timing, duration and manifestation of pain, aggravating and relieving factors, gynecologic history, and family history.
• Primary dysmenorrhea causes cramping pelvic pain that lasts a maximum of 3 days and is typically responsive to NSAIDs.
• Secondary dysmenorrhea has variable history and clinical presentations.
• For a physical examination: primary dysmenorrhea is typically normal, while secondary dysmenorrhea has positive findings on examination.
• Imaging has little significance in evaluating primary dysmenorrhea, but it can differentiate secondary causes.

Primary Dysmenorrhea vs Endometriosis in the Adolescent

• Investigate secondary causes if there is no clinical improvement within 3-6 months of therapy initiation.
• In adolescent females, the most common cause of secondary dysmenorrhea is endometriosis.
• Endometriosis should be considered in patients with persistent, clinically significant dysmenorrhea despite treatment.

Secondary Dysmenorrhea

• It is menstrual-related pain due to underlying pelvic or abdominal pathology, such as endometriosis and adenomyosis.
• Other causes include uterine leiomyomas (fibroids) or uterine polyps, pelvic inflammatory disease (PID) or pelvic adhesions, and obstructive vaginal or uterine congenital anomalies.
• Cervical stenosis and ovarian cysts may also cause secondary dysmenorrhea.
• differentials to consider (including non-gynecologic) include ectopic pregnancy, and a malpositioned intrauterine device (IUD).
• Urinary tract infection (UTI), interstitial cystitis, and irritable bowel syndrome are also differentials.
• Musculoskeletal causes can also contribute.

Endometriosis

• It is a chronic, estrogen-dependent condition characterized by ectopic implantation of functional uterine tissue outside the uterine cavity.
• It affects 10-15% of reproductive-age females, with 70% experiencing chronic pelvic pain.
• Up to 50% of women with endometriosis experience female infertility.
• Risk factors include: menarche before 11 years, menstrual period less than 27 days, menorrhagia, and nulliparity.
• Peak incidence is 25-29 years, with Caucasians more often affected than those of African descent.
• It can be asymptomatic with chronic and cyclic pelvic pain, dysmenorrhea, dyspareunia, dysuria, dyschezia, sub-fertility or infertility, or possibly hyperalgesia.
• CA125, TVUS, and MRI are all means of diagnosis.
• Tenderness on vaginal exam, palpable nodules in posterior fornix and/or adnexal mass, and uterine immobility may also contribute to diagnosis.
• Co-manage with an endocrinologist for pharmacology and/or surgical options.
• The prognosis consists of 6-8X risk infertility, miscarriage (OR 1.81), and endometrial cancer risk (RR 1.6).
• 3 subtypes consist of: endometrioma, deep infiltrating endometriosis, superficial peritoneal endometriosis

Endometriosis - History and Physical Exam

• History of any 1 of 4 symptoms (pelvic pain, dysmenorrhea, dyspareunia, and infertility): Sensitivity 76%, LR + 1.81, LR - 0.41
• History of pain that increases during menses + infertility: Sensitivity 20%, LR + 10.0, LR - 0.82
• Palpable abnormality in rectovaginal septum*: Sensitivity 88%, LR + 8-88, LR - 0.13
• Palpable abnormality in Pouch of Douglas*: Sensitivity 70%, LR + 6.36 - 70, LR - 0.34
• Palpable abnormality in uterosacral ligaments*: Sensitivity 73%, LR + 2.61, LR - 0.38 Palpable abnormality = palpable nodularity, thickened or stiffened tissue, or cyst
• deep (infiltrating) endometriosis

Endometriosis - Imaging and Laboratory

• TVUS (endometrioma / ovary endometriosis): Sensitivity 93%, LR + 23.25 LR - 0.07
• TVUS (deep endometriosis): Sensitivity 79%, LR + 13.17, LR - 0.22
• TVUS - SonoPODography (superficial): Sensitivity 65%, LR + 64.9, LR - 0.35
• MRI (retrosigmoid endometriosis): Sensitivity 63-98%, LR + 5.73-98, LR - 0.02-0.42
• Laparoscopy: Sensitivity 94%, LR + 4.48, LR - 0.08
• Histology (reference standard): Definitive

Adenomyosis

• Ectopic endometrial tissue is found within the uterine myometrium.
• It is estimated 20-35% of females.
• Increased estrogen exposure (increased parity, early menarche, short menstrual cycles, elevated BMI, OCP use, tamoxifen use) and prior uterine surgery are risk factors.
• Presenting symptoms may consist of dysmenorrhea, menorrhagia, chronic pelvic pain, dyspareunia, and it may also be asymptomatic.
• TVUS is the preferred means of diagnosis.
• On a pelvic exam findings consist of a "boggy" enlarged uterus, that is possibly tender.
• CBC, ferritin may reveal possible anemia with menorrhagia.
• Co-management with endocrinologist and hysterectomy are potential options.
• Commonly coexists with (leiomyoma 50%, endometriosis 11%, endometrial polyps 7%).

Adenomyosis - Imaging and Laboratory

• TVUS (adenomyosis): Sensitivity 89%, LR + 8.09, LR - 0.12
• MRI (adenomyosis): Sensitivity 86%, LR + 6.14, LR - 0.16
• Histology (reference standard): Definitive

Uterine Leiomyomas (Fibroids)

• A group of benign smooth muscle tumors.
• It is estimated 70-80% of females by age 50.
• Early menarche, use of oral contraceptives before age 16 years, increased BMI, and African descent are risk factors.
• Asymptomatic or pelvic pain, pressure, and abnormal vaginal bleeding (AUB) may also contribute.
• Enlarged, irregularly shaped uterus Diagnosis consists of history, physical exam, TVUS
• CBC, ferritin reveal anemia if abnormal uterine bleeding (AUB),
• Co-manage with reproductive endocrinologist or gynecologist.
• Varies based on location of fibroid, may cause 2-3% female infertility.

Uterine (Endometrial) Polyp

• Refers to overgrowths of endometrial glands and stroma within the uterine cavity.
• Found among 20-40% of females with AUB.
• Risk factors include unopposed estrogen, chronic tamoxifen use, in women ages 40-49 years.
• An indicator is abdominal/pelvic discomfort/pain or asymptomatic AUB.
• Physical exam, TVUS, and tissue sampling are means of diagnosis.
• Pelvic exam (speculum, bimanual): pedunculated endometrial polyp may be visualized from the external os
• hCG, CBC, coagulation panel (INR, aPTT, Fibrinogen) may indicate anemia or coagulopathy
• Prognosis includes majority benign, but risk of malignancy increased with age greater than 60, large-size of polyp, postmenopausal status, symptomatic bleeding and PCOS. The recurrence rate is approx. 2.5-3.7% and may impair fertility (conflicting data).

Pelvic Inflammatory Disease(PID)

• Describes the inflammation of the upper genital tract (uterus, fallopian tubes, and/or ovaries) due to infection (most often polymicrobial).
• 10-15% of reproductive-aged females experience 1 episode; peak incidence 15-25 years.
• Risk factors include sexually transmitted bacteria(sexually active, unprotected intercourse, new or multiple partners, <15 years at onset of sexual activity)
• Patients can be asymptomatic or pelvic/lower abdominal, vaginal discharge, dyspareunia, and/or abnormal uterine bleeding, increased urinary frequency or dysuria can develop.
• Diagnosis: history, physical exam, vaginal swabs
• Possible Nucleic Acid Amplification Test (NAAT) for gonorrhea or chlamydia.
• ESR, CRP is often elevated.
• Pelvic exam (speculum, bimanual): adnexal and/or uterine tenderness, cervical discharge, (+) cervical motion test, cervical or vaginal mucopurulent discharge
• 25% may develop chronic pelvic pain, 10-50% impaired fertility, 15-60% ectopic pregnancy
• PID physical exam:
  • Purulent endocervical secretion has Sensitivity 23%, LR + 3.3, LR - 0.8
  • Rebound tenderness has Sensitivity 25%, LR + 2.5, LR - 0.8
  • Cervical motion test has Sensitivity 72%, LR + 1.44, LR - 0.56
  • Pelvic tenderness has Sensitivity 81%, LR + 1.35, LR - 0.47
  • Adnexal tenderness has Sensitivity 87%, LR + 1.19, LR - 0.48
  • TVUS (PID) has Sensitivity 30%, LR + 0.91, LR - 1.04
  • NAAT positive for N. gonorrhea or Chlamydia has Sensitivity 89-98%, LR + 45-98, LR - 0.02-0.11

(Functional) Ovarian Cysts

• Fluid-filled structures that may be simple or complex.
• Affects approximately 7-8% of females aged 24-40 years.
• Risk factors include fertility treatment, Tamoxifen, pregnancy, hypothyroidism, maternal gonadotropins, smoking, and tubal ligation.
• Asymptomatic with unilateral pain/pressure in the lower abdomen, which may be intermittent or constant and characterized as sharp or dull.
• With rupture - acute, severe pain possibly with N/V.
• Diagnosis: often incidentally found on imaging, TVUS
• hCG and UA - rule out: pregnancy and UTI.
• Cancer antigen 125 (CA125)
• Pelvic exam (bimanual) - possibly a palpable, enlarged, and tender ovary.
• Management: co-management with gynecologist
• Prognosis: 70-80% of follicular cysts resolve spontaneously; ovarian cysts can lead to complications such as pelvic pain, cyst rupture, hemorrhage, and ovarian torsion.

Ectopic Pregnancy

• Occurs when the implantation of an embryo outside of the uterine cavity; which occurs most commonly in the fallopian tube (> 90% of ectopic pregnancies).
• Found to be in 1-2% of the general population.
• More common in 2-5% of females utilizing ART.
• Risk include advanced maternal age, smoking, Hx of ectopic pregnancy/tubal damage/tubal surgery, prior pelvic infections, DES exposure, IUD use, and assisted reproductive technologies.
• Resulting symptoms consist of pelvic or abdominal discomfort/pain, nausea/vomiting, syncope, lightheadedness, and vaginal bleeding.
• Diagnosis: hCG, TVUS
• Vital signs (possible tachycardia and/or hypotension)
• Abdominal exam: suprapubic tenderness, possibly guarding,
• Pelvic exam (speculum, bimanual): palpable nodular adnexa and/or adnexal mass
• Management: referral to ER (emergent), hcg trending until non-pregnant level
• Prognosis: 100% mortality for developing embryo, which is the leading cause of maternal mortality in first trimester (9-14% of cases) and accounts for 5-10% of all pregnancy-related deaths.

Interstitial Cystitis / Bladder Pain Syndrome (IC / BPS)

• Complex, chronic condition characterized by inflammation of the bladder’s lining
• Possibly 2.7% of female and 1.9% of men are affected in the US.
• In women, it affects women ages 50-59 years.
• In men, it affects men ages 56-74 years
• Suprapubic pelvic discomfort/pressure/pain > 6 weeks (worse with bladder filling, relieved with urination), severe urinary frequency, urinary urgency, nocturia; possibly dysuria, dyspareunia.
• Is characterized as a diagnosis through: (1) CBC, FBS, HbA1c, electrolytes (Na, K), Creatinine/eGFR, ALT, Albumin 2. Urinalysis and urine culture - typically negative 3. Neurological exam: tone, reflexes, power, sensation, cranial nerve testing 4. Pelvic exam, possibly cystoscopy (with or without hydrodistention and biopsy)
• Management: comanagement should be considered alongside a urologist and pelvic floor physiotherapist.
• Prognosis: symptoms may remain unchanged for up to 9 years, resulting in psychological and social health deterioration through sleep disturbance, sexual dysfunction, anxiety and depression.

Irritable Bowel Syndrome (IBS)

• Recurrent abdominal pain at least 1 day per week in the last 3 months.
• Associated with at least two of the following: defecation, a change in stool frequency, and/or a change in stool appearance(form). [ROME IV criteria]
• Psychologic distress and a history of gastroenteritis are common.
• Alternated motility (constipation or diarrhea), cramping in the lower quadrants which is relieved BM, distention, sensation of incomplete evacuation, mucous with stool, urgency; fatigue, headaches, disturbed sleep, anxiety and/or depressed mood.
• Diagnosis: history and physical exam, in alignment with the ROME IV criteria.
• Diagnostic testing to consider: CBC, BMP (FBG, Ca, Electrolytes (Na, K, CO2, Cl), BUN, Creatinine), CRP;
• Consider anti-tTG IgA, total IgA, O&P, fecal calprotectin, TSH, LFTs
• Management: patient education (dietary and lifestyle modification. Symptoms can deteriorate 2-18% and 14-20% fecal incontinence.

Gynecological Differentials Include:

• Primary dysmenorrhea
• Endometriosis
• Adenomyosis
• Pelvic inflammatory disease
• Obstruction of the reproductive tract
• Ovarian or adnexal cysts
• Asherman syndrome
• Ectopic pregnancy
• Membranous dysmenorrhea

Non-Gynecological Differentials Include

• Irritable bowel syndrome
• Urinary tract infection
• Interstitial cystitis
• Musculoskeletal causes

Primary Dysmenorrhea Facts

• There is no identifiable pelvic pathology.
• More severe in young, nulliparous women.
• Onset is within 2 years after menarche.
• Tends to improve with age.
• More common in people who smoke.
• Pain is relieved by NSAIDs or ovulation suppression (OCP).

Secondary Dysmenorrhea Facts

• It is associated with pelvic pathology.
• Onset age is variable, and is more suspected in women over 25 years with no prior history of dysmenorrhea.
• Only partial symptomatic improvement with NSAIDs.

Membranous Dysmenorrhea

• It is a rare condition characterized by intense cramping and passage of a cast of the endometrium.

dysmenorrhea

• Dysmenorrhea is pelvic pain that occurs with menses, often described as cramping in quality

Evaluation and Treatment

• First, assess if the history is consistent with primary dysmenorrhea (normal pelvic exam findings, negative urinary hCG).
• If so, begin a trial of nonsteroidal anti-inflammatory drugs (NSAIDs) or oral contraceptive pills (OCPs).
• If symptoms are relieved, continue therapy and reassess every 6 months.
• If not, perform lab testing (gonorrhea and chlamydia testing, urinalysis, ESR, CBC).
• If positive findings result, treat pelvic inflammatory disease (PID).
• If lab results are negative, perform pelvic ultrasonography.
• If positive findings result, treat the pathology detected.
• If pelvic ultrasonography results are negative, reassess clinical history for changes and consider CT, MRI, hysteroscopy, or laparoscopy based on clinical suspicion.
• If these tests bring positive results, treat the pathology detected.
• If these tests result is continue to be normal, consider chronic pelvic pain and a multidisciplinary approach.

Management

• It's important to explain that primary dysmenorrhea is a common phenomenon.
• Validate the patient's concerns and offer symptomatic treatment.
• Reassuring that pain does not indicate an organic process or abnormality.
• If an organic cause is suspected, further investigation and targeted therapy are indicated.
• Pharmacotherapy fails in about 20% of patients, and often require a referral for further investigation.
• Multidisciplinary team approach: naturopathic doctor, family doctor, pharmacist, gynecologist, reproductive endocrinologist and/or surgeon, pelvic floor physiotherapy, and psychotherapist/counselor
• Cases that fail to be managed with pharmacotherapy and/or conservative surgery may need further surgical intervention to obtain relief.

Primary Dysmenorrhea Consensus Guideline (SOGC)

• Both primary and secondary dysmenorrhea are likely to respond to the same medical therapy.
• Health care providers should include questions regarding menstrual pain when obtaining a woman's medical history.
• A pelvic exam is not necessary before initiating therapy.
• A pelvic exam is indicated if organic pathology is suspected and in patients without response to conventional therapy.
• First-line treatment is administering non-steroidal anti-inflammatory drugs in regular dosing regimens.
• Hormonal therapies should be offered if the patient is not currently planning pregnancy and has no contraindications.
• Continuous or extended use of combined hormonal contraceptives CHCs is recommended.
• Regular exercise is likely and should be recommended to improve symptoms of dysmenorrhea.
• Using local heat via heated pads or patches should be recommended.
• Using High-frequency transcutaneous electrical nerve stimulation could be tried as a complementary treatment.
• Acupoint stimulation could provide some benefit.
• Ginger may have value when combined with alternative therapies.
• Preoperative workups should include a medical history, exam, ultrasound and or MRI in order to attempt to discovered a secondary cause which will allow therapies to be more targeted.
• Surgery should be reserved to difficult cases after therapies have been tried.

Prognosis

• Primary dysmenorrhea presents as a recurring condition and improves by the third decade of life or after childbirth.
• Patients generally respond well to NSAID and/or nonpharmacologic therapies.
• Secondary dysmenorrhea depends on the specific condition and complications.
• Secondary dysmenorrhea can include Infertility, pelvic organ prolapse, Menorrhagia, and Anemia

Psychological Considerations

• Psychological disorders (depression, anxiety, stress) may have a bidirectional association with dysmenorrhea
• Experiencing monthly repeated menstrual pain may increase the risk of developing depression, anxiety or stress.
• Severe dysmenorrhea was found to have a high risk of depression.
• Primary dysmenorrhea was associated with a significant depressive disorder.
• Experiencing depression may increase the likelihood of experiencing dysmenorrhea.
• Psychological distress may be associated with increased sensitivity to pain and a reduced response to medication.
• Chronic pelvic pain has been associated with both depression and anxiety.

Impact

• Primary dysmenorrhea is not life-threatening, but can lead to significant disability.
• Limits daily activities in 16-29% of females.
• Leading cause of recurrent short-term absenteeism from school among adolescent females.
• 34-50% rate of absenteeism in females under the age of 30 years.
• Secondary dysmenorrhea is associated with significant impairment in the quality of life
• A 5% rate of absenteeism from work in women over age 30 years.
• It is associated with increased healthcare costs.

Management in Young Females

• Empiric therapy to address patient symptoms should be initiated for a trial of at least 3-6 months before initiating a different therapeutic approach.
• If symptom management fails, and referrals to specialist may be needed.
• Secondary causes of dysmenorrhea will need investigative and therapeutic choices based on symptom presentation, suspected type of secondary dysmenorrhea and severity of pain.