Disorders of Menstruation Abnormal Uterine Bleeding Tory Davis

Disorders of Menstruation / Abnormal Uterine Bleeding Tory Davis, PA-C

Menstruation Shedding the uterine lining (endometrium) if pregnancy does not occur. Necessary (in the absence of hormonal regulation) to insure the endometrium does not become hyperplastic.

Terminology Amenorrhea—lack of menstrual bleeding – Primary—no menses by age 16 – Secondary—absence of 3 or more expected menstrual cycles Break-through bleeding (BTB) unexpected bleeding usually occurring while a woman is on exogenous hormonal medication (eg OCPs, patch, or ring)

Terminology (cont. ) Menorrhagia—heavy menstrual bleeding. Prolonged or excessive menstrual blood loss with regular cycles Metrorrhagia—irregular, frequent bleeding Menometrorrhagia—irregular menses with prolonged or excessive blood loss Midcycle bleeding—light menstrual bleeding occurring in ovulatory women at the midcycle estradiol trough

Terminology (cont. ) Oligomenorrhea-- menstrual bleeding/menses occurring less frequently than 36 days apart Polymenorrhea—frequent menstrual bleeding/menses occurring more frequently than 21 days apart Contact bleeding/post-coital bleeding Dysmenorrhea- painful menstrual bleeding

Physiologic Requirement? Hormonal fluctuations of the cycle allow the monthly release of a mature ovum from the ovaries and prepares the endometrium for implantation. Controlled by Gn. RH from the hypothalamus, FSH and LH from the pituitary, E 2 from the ovary, and P 4 from the corpus luteum

Normal Menstrual Cycles Mature, ovulatory women – 28 -29 day average – 21 -36 day range – 2 -7 days duration – 20 -80 cc of blood loss per month

Cycle Variation Women in their middle reproductive years have the most predictable cycles More pronounced cycle to cycle variability in the 5 -7 years after menarche and 6 -8 years before menopause

Cycle Variation (cont. ) Adolescents – Majority range 21 -48 days – Usually anovulatory – Mean time from menarche until half the cycles are ovulatory depends upon the age of menarche – 12 yrs 1 yrs till half cycles are ovulatory – 12 -13 3 yrs – >13 4. 5 yrs

Cycle Variation (cont. ) Perimenopause – Cycles initially shorten – Ultimately (apparently) lengthen, as an entire cycle will be skipped Average of menopause is 51 – Cessation of menses for one year

Impact on Health 75% of women experience physical changes associated with menses PMS (Premenstrual syndrome) PMDD (Premenstrual dysphoric disorder) Direct and indirect health care costs – Visits to ED, clinic, or office – Time lost from work

Quality of Life Issues Many women seek healthcare related to menstrual problems – National health survey revealed 66% of women sought care – 31% had stayed in bed for more than ½ day at least once during the previous year – 12% of all ED visits

PMS Psychoneuroendocrine d/o with biological, social and psychological impacts Up to 75% of women experience some level of recurrent sx Up to 5% may experience severe sx and distress

Common PMS Sx Headache Breast pain Bloating Irritability Fatigue Crying Abd pain Clumsiness Sleep alteration Labile mood Social withdrawal Libido change Appetite change

Requisite Symptoms for PMDD Diagnosis Depressed mood Anxiety/tension Mood swings Irritability Decreased interest Concentration difficulties Fatigue Appetite changes/food cravings Insomnia/hypersomnia Feeling out of control Physical symptoms 5/11 symptoms needed for diagnosis and Sx disrupt daily functioning

PMS/PMDD Tx Limit caffeine, tobacco, alcohol and sodium Frequent high-complex carb meals CBT, stress management, aerobic exercise

PMS/PMDD Tx SSRIs (ie: fluoxetine) 14 days prior to onset of menses OCPs. . not really effective Chaste berry and St John’s wort- more effective than placebo but less than fluoxetine

Dysmenorrhea Painful menstruation- when pain prevents normal activity and requires medication Pain starts when bleeding starts Prostaglandin activity Emotional/psychological factors

Dysmenorrhea tx NSAIDs, starting a day before period – Ibuprofen, naproxen Anti-prostaglandins much less effective after pain is established Continuous heat to abd OCPs for 6 -12 months have lasting benefit

Abnormal Uterine Bleeding Menorrhagia Oligomenorrhea Metrorhhagia Polymenorhhea Menometrorhhagia Oligomenorrhea Contact bleeding

Ddx of Abnormal Uterine Bleeding Blood Dyscrasias Anatomic causes of bleeding, including pregnancy Anovulation Malignancy Non-uterine causes of bleeding

AUB work-up Hx PE with cytology Pelvic ultrasound Endometrial biopsy Hysteroscopy D & C

Blood Dyscrasias Von Willebrand Idiopathic thrombocytic purpura (ITP) Leukemia Clotting factor deficiencies

Anatomic causes Pregnancy—cessation of menstrual bleeding for 40 weeks – 1 in 5 pregnancies end in spontaneous abortion – First symptom is usually bleeding Gestational trophoblastic disease (molar pregnancy) – Non-viable pregnancy with a large, grapelike placenta that sloughs off and causes heavy bleeding Infection – Cervicitis—leads to bleeding from the cervix – Endometritis—leads to sloughing off of endometrial blood and mucous

Anatomic causes (cont. ) Endocervical or endometrial polyps – Esp post-coital bleeding IUD – Bleeding likely with Paragard, extremely rare with Mirena (progestin-containing) Leiomyoma (fibroids) – Subserosal (in wall of myometrium) – Intramural (most common “bump on top”) – Submucosal (can be pedunculated)

Leiomyomas (Fibroids) Benign neoplasms arising from uterine wall smooth muscle cells 20 -25% of reproductive age women Can be small to quite large, single or multiple. Surrounded by pseudocapsule. Often asx, but can cause metrorrhagia, menorrhagia, dysmenorrhea and infertility Cause unknown, but hormone responsive

Fibroid Sx Prolonged, heavy bleeding, can cause anemia – (which type? ) Pain- from vascular compression Sensation of fullness, heaviness in pelvis Infertility or spontaneous abortion PE: – Distorted uterine contour – Confirm with ultrasound

Fibroid Tx Depends on sx, age, parity, reproductive plans, general health, and size/location of leiomyomas Gn. RH agonists- to shrink fibroid OCPs control bleeding but do not treat the fibroid Progestin-releasing IUD for multiple small leiomyomata

Fibroid Tx - Surgical Myomectomy- preserves fertility, high risk for fibroid recurrence Hysterectomy- eliminates sx and chance of recurrence. Also eliminates uterus. Uterine fibroid embolization (UFE) – Embolic occlusion of uterine arteries – As effective as above, few recurrences, few major complications

Anovulation Patient History—very important to diagnosis – Ovulatory cycles—consistent number of days from beginning of one cycle to the next, breast tenderness, and dysmenorrhea usually present – Anovulatory cycles—variation in number of days per cycle, no breast tenderness, and dysmenorrhea is not consistent from one cycle to the next

Anovulation Hypothalmic disorder related to: – Stress – Diet – Exercise – Body fat Pituitary-ovarian axis very sensitive to any bodily changes

Anovulation: Endocrinopathies Thyroid – Both hypo- and hyperthyroidism may present with AUB – TSH

Anovulation, endocrinopathies Prolactin – Pepperell evaluated 304 patients with oligoamenorrhea and found 7. 6% had increased prolactin – Interrupts menstrual function by inhibiting pulsatile release of Gn. RH – Note: causes for falsely elevated prolactin levels Recent breast exam or breast stimulation Recent pelvic exam

Anovulation: POF Premature Ovarian Failure (Early Menopause) – Diagnosed if woman of child-bearing age develops amenorrhea and FSH level is found to be greater than 35 – This is an indication that the ovaries are no longer producing sufficient hormone levels to allow ovulation to occur

Other Causes of Anovulation Any medication that affects the cytochrome P-450 cycle, eg psychotropic drugs Ovarian tumors that produce steroids: – Granulosa cell tumors – Sertoli Leydig cell tumors

Malignancy as a Cause of AUB Uterus—endometrial cancer Cervix--severe dysplasia, carcinoma in situ, or invasive cancer will lead to bleeding. Fallopian tubes—much less common Ovarian—not usually associated with bleeding

DUB “Dysfunctional uterine bleeding” Abnormal uterine bleeding with pathologic causes ruled out So. . you’ve done all that stuff, and it’s all okay Usually tx with hormones (ie OCPs) to control bleeding

Non-uterine causes Genital neoplasms of the vulva or vagina – To avoid missing vaginal lesions, stainless steel speculum blades should be rotated on removal to fully evaluate the vaginal mucosa – Better: use plastic speculum with good light source Genital trauma/foreign objects Rectal bleeding or urinary tract source

Evaluation History – Menstrual pattern (duration, changes in quality, color of menses) – Dysmenorrhea, mittleschmerz, breast changes – Post-coital spotting – Dietary practices, change in weight, exercise, stress – Evidence of systemic disease

Evaluation (cont. ) Physical Exam – – – – Vital signs, height, weight, body phenotype, BMI Skin, hair (acne, hirsutism pattern) Fat distribution, striae Thyroid Breast exam to check for galactorrhea Complete pelvic exam Tanner stage for teens

Evaluation--testing All patients: – Pregnancy test – CBC with platelets – Recent Pap Over 35 yrs: – Endometrial sample Documented drop in hgb <10 – PT, PTT – Bleeding time As indicated: – – – TSH Prolactin Testosterone LH/FSH 17 -OH progesterone Overnight dexamethasone suppression test or 24 hr urinary free cortisol – Hysteroscopy or ultrasound

Proposed Treatment Scheme Begin evaluation and diagnostic testing, rule out pregnancy, check hgb Hospitalize for low hgb (<7), and strongly consider blood dyscrasia, submucosal fibroid, or malignancy

Acute Bleeding: Control Oral progestins: – Micronized Progesterone 200 mg (Prometrium) or Medroxyprogesterone 10 mg (Provera) or Norethindrone 5 mg (Aygestin) – 1 po q 4 hrs or until bleeding stops, then – 1 qid x 4 days – 1 tid x 3 days – 1 bid x 2 weeks, then – Cycle monthly with progestin or low dose oral contraceptive

AUB Long Term Control Cycle with low dose OCP, patch, or vaginal ring Cycle with a progestin, eg Prometrium Use of progestin-containing IUD (Mirena) Choice depends upon: – – Contraceptive need Smoking status Medical history Patient preference

Long Term Control Danazol or other androgen agents will shut down the hypothalamic-pituitary-ovarian axis Gn. RH analogs (Lupron, Nafarelin) (x 6 months) Ibuprofen and other NSAIDs decrease bleeding and cramping Endometrial thickness of 4 mm or less is needed to eliminate intermenstrual bleeding

Endometrial Ablation Uterine thermal balloon – – Out-patient procedure Regional anesthesia (spinal or epidural) Balloon catheter inserted into uterus Very hot fluid (87 C) is inserted for 8 minutes Post-Procedure – Cramping, bleeding for 1 week, serous discharge for 4 -6 weeks – Amenorrhea is the intended result

Endometriosis Abnormal growth of endometrial tissue in locations other than the uterine lining 3 -10% of women of reproductive age 30% of infertile women

Pathogenesis Cause unknown, but theories: Retrograde menstruation – Viable endometrium shed during menses, flows thru fallopian tubes to peritoneal cavity – Solid theory that does not explain all cases (ie: endometriosis in nonmenstruating women or in non-peritoneal endometriosis)

Pathology This is a SURGICAL diagnosis Characteristic diagnostic surgical gross appearance Small petechial lesions to larger “powder burn” lesions 5 -10 mm – Multiple lesions On ovary, can enlarge to several centimeters – Endometriomas, or “chocolate cysts”

Implantation MC site: ovary Also round and broad ligaments, uterus, fallopian tubes, sigmoid colon, appendix Can implant on bowel, bladder, ureters – Or deep in tissue; cervix, posterior fornix, wounds Also brain, thoracic cavity. . .

Pathophys Pelvic pain- secondary to hormonal stimulation of endometrial tissue Implants enlarge and then bleed – But implants are surrounded by fibrotic tissue that prevents escape of hemorrhagic fluid Leads effects to inflammation, adhesions, mass

BUT Many pts with endometriosis do not have significant pain Maybe pain is assoc with depth of invasion?

History Infertility Dysmenorrhea Dyspareunia Constant pelvic pain or low sacral back pain

Physical Tender nodules in posterior fornix Pain with uterine motion Or – most likely- normal exam

Diagnosis What kind of diagnosis is it? Can suspect and even tx based on clinical findings But if you need to know, go in- usually laparoscopically No need for other studies usually

Endometriosis Tx Take into account: – Desire for fertility – Age – Symptoms – Stage of disease

Tx Analgesics (ibu) Hormones – OCPs or progestins – Danazol- prevents gonadotropin release, inhibits midcyle LH and GSH. Androgenic side fx – Gn. RH agonists (Lupron)- with continuous admin, suppresses gonadotropin secretion Assisted reproduction when desired

Prognosis Can offer significant relief from sx Can help achieve pregnancy Cannot cure – Although extensive surgery can come close – Conservative surgery has 10 -35% recurrence

Amenorrhea Absence of menses Primary amenorrhea- no menses by age 16 with otherwise nl development Secondary amenorrhea- absence of menses for 3 or more cycles or 6 months in a previously menstruating female – MC cause? ? – 3% in genl population – 100% under extreme stress Examples?

Why bother? Dx and tx amenorrhea important – Implications for future fertility – Risks of unopposed estrogen or hypoestrogen

Ddx Hypothalamic defects – Abnl Gn. RH pulse discharge, transport – Congenital Gn. RH deficiency Idiopathic hypogonadotropic hypogonadism Pituitary defects (less common) – Congenital or acquired ie pituitary adenomas

Ddx Ovarian Dysfunction – Gonadal dysgenesis- MC cause of primary amenorrhea ie: Turner’s syndrome – POF – PCOS XY karyotype (androgen insensitivity syndrome)

Work-up Download Amenorrhea pdf posted to shared files

Progesterone challenge Indirectly determines if ovary is producing estrogen If endometrium has been primed, exogenous progestin will produce menses

Tx Desiring pregnancy? – Ovulation induction Not desiring pregnancy? – If hypoestrogenic, combo tx with estrogen and progesterone to maintain bone density and prevent genital atrophy – Normal progestin challenge: needs occasional progestin to prevent endometrial hyperplasia and cancer – OCPs work well for either, and can decrease hirsutism – Calcium, too!

Infertility vocab Infertility: Inability of a couple to conceive for 12 months. (implies decrease in ability to conceive) – Primary vs secondary Sterility: intrinsic inability to conceive Fecundity: probability of achieving live birth from one menstrual cycle – Fecundability- likelihood of conception per month Very few infertile patients are sterile (1 -2%)

Epi 13% of women (range 7 -28%, age dependant) Incidence of primary and secondary infertility increasing – Why? 90% of couples having regular unprotected intercourse will conceive in 1 year Normal fecundability 20 -25%

Infertility etiology Either or both partners – Cause found in 80% with even split between partners So start with thorough hx of conception attempts and thorough hx of BOTH partners

Key Aspects Sperm Oocyte- ovarian reserve and ovulation Transport- fallopian tubes Implantation- uterus

Dudes History – Prior paternity – Congenital abnormalities or undescended testes – Prev surgery or infections PE – Varicocele (MC cause) Semen analysis – Sperm count – Motility – Morphology

Chicas Hx – Menarche – Cycle length and characteristics – S/s systemic ds (hypothyroid) – Exercise, weight – Age

Girl exam Pelvic, pap, etc Confirmation of ovulation – History – U/S ovulation confirmation – Basal body temp – Cervical mucus monitoring Pelvic U/S, hysterosalpingogram, maybe laparoscopy

Treatment Understanding that infertility can be a devastating diagnosis Emotional roller coaster Damaging to self-image, relationships, intimacy

Tx Sperm factor- can use donor sperm or intrauterine insemination using “prepared” sperm Ovulatory factor – Clomiphene citrate (Clomid) for ovulatory induction – Good place to start – IVF (most invasive/expensive) Referral is most appropriate