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Postmenopausal Bleeding

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OBGYN Clerkship Session Level Objectives

Post-Menopausal Bleeding

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  • Define Postmenopausal Bleeding (PMB)
  • Differential Diagnosis
  • Approach & Work-up
  • Treatment of Individual Concerns

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BACKGROUND | Definitions

MENOPAUSE

Cessation menstrual periods after 12mo Amenorrhea* | Normal onset ~age 51

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PERIMENOPAUSE

Irregular menses up to 1yr post-regular menstruation (avg. duration ~4yrs)

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POSTMENOPAUSAL BLEEDING (PMB)

Bleeding occurring after menopause

  • Prevalence: 4-11% of postmenopausal women
  • Accounts for 5% of gynecologic office visits

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CASE

What further information is required?

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  • Medical History
  • Surgical History
  • Gynecological History
  • Obstetrical History

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  • 59-Year-Old
  • Gravida(G): 3
  • Para (P): 2

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Presents to the office with self-reported 3 months of intermittent vaginal bleeding (spotting). Recently she has noticed some larger quantities and small clots.

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CASE

MHx & SHx

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  • cHTN (1°)
  • BMI 32 (Class II)
  • Appendectomy

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Gynecologic Hx

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  • Menarche 12yo
  • Menses
    • q25d, regular
    • 4d heavy, 1d moderate
    • Prior OCP Contraceptive
    • Menopause age 54

Obstetrical Hx

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  • 2x SVD, Uncomplicated
  • 1x SAB

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  • 59-Year-Old
  • Gravida(G): 3
  • Para (P): 2

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Presents to the office with self-reported 3 months of intermittent vaginal bleeding (spotting). Recently she has noticed some larger quantities and small clots.

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CASE

DIFFERENTIAL

  • Endometrial Cancer (6.6%)
  • Endometrial Hyperplasia (2.2%)
  • Polyps (37.7%)
  • Fibroids (6.2%)
  • Vaginal or Endometrial Atrophy (30.8%)
  • Cervical Cancer
  • Hormonal Therapy
  • Other

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  • 59-Year-Old
  • Gravida(G): 3
  • Para (P): 2

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Presents to the office with self-reported 3 months of intermittent vaginal bleeding (spotting). Recently she has noticed some larger quantities and small clots.

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CASE

APPROACH

History

  • General symptoms: Abdominal pain, Dyspareunia
  • Bleeding: Onset, Duration, Amount
  • Menstrual History: Age of Menarche, Age of Menopause, Bleeding characteristics.
  • Medical and Surgical History
  • Family Medical History, specifically Lynch/Peutz Jeughers/Cowden

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Physical

  • BMI
  • Abdominal Exam ⇒ Uterine size, Abdominal Tenderness, Ascites.
  • Pelvic Exam ⇒ Uterine size, Uterine mobility, Adnexal abnormalities
  • Speculum

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  • 59-Year-Old
  • Gravida(G): 3
  • Para (P): 2

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Presents to the office with self-reported 3 months of intermittent vaginal bleeding (spotting). Recently she has noticed some larger quantities and small clots.

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CASE

WORKUP

  • Ultrasound (ideally Pelvic)
  • Measure by evaluating Endometrial Stripe (ETT)
    • Average in postmenopausal women >5mm, can be up to 8-11mm
    • Biopsy (bx) if >11mm NO MATTER WHAT
    • < 4mm, NPV >99% for endometrial cancer, no need for bx

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-unless-

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  • Recurrent bleeding or multiple RFs
  • If perimenopausal will still bx with above criteria

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  • 59-Year-Old
  • Gravida(G): 3
  • Para (P): 2

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Presents to the office with self-reported 3 months of intermittent vaginal bleeding (spotting). Recently she has noticed some larger quantities and small clots.

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CASE

ULTRASOUND SHOWS ENDOMETRIAL STRIPE 12MM

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(Also ongoing PMB + BMI 31 + later menopause)

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  • 59-Year-Old
  • Gravida(G): 3
  • Para (P): 2

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Presents to the office with self-reported 3 months of intermittent vaginal bleeding (spotting). Recently she has noticed some larger quantities and small clots.

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ENDOMETRIAL BIOPSY

  • All post-menopausal bleeding and Abnormal Uterine Bleeding requires an Endometrial biopsy

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  • In office bx with Pipelle
    • Factors/risks to review with pt: pain, bleeding, risk of perforation, infection, false negative (~5-15%, SOGC 249)
    • Feasibility interference: virginal status, cervical stenosis, small introitus, pain, anatomical abnormalities (e.g. fibroids), obesity.

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  • Hysteroscopy & Dilation + Curettage (D&C)
    • Done under anesthetic
    • False negative rate 2-6%

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ENDOMETRIAL BIOPSY: RESULTS

  • Results: negative/normal, Hyperplasia, cancer.

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  • 2 Classifications as per WHO Classification
    • Non-atypical Hyperplasia
      • Not pre-malignant, rarely progresses to endometrial cancer (1-3%, SOGC 390)
      • 4x risk endometrial cancer compared to normal

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  • Atypical Hyperplasia = Endometrial Intraepithelial Neoplasia (EIN)
    • Precursor for Endometroid Endometrial Carcinoma
    • ⅓ patients will have Carcinoma dx within 1 year
    • Microscopically ⇒ glandular crowding with Cytologic Atypia
    • Needs definitive management

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ENDOMETRIAL HYPERPLASIA/CANCER RISK FACTORS

  • Menstrual factors
    • Early Menarche
    • Late Menopause
    • Anovulation
    • Nulliparity
    • Infertility
    • PCOS
  • Iatrogenic
    • Unopposed Exogenous Estrogen
    • Tamoxifen
  • Comorbidities
    • Age
    • Obesity
    • Diabetes
    • HTN
    • Genetics (e.g. Lynch, Cowden, Peutz-Jeghers)
  • Smoking
  • Progesterone based contraceptive use
  • History of induced abortion

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INCREASES RISK

DECREASES RISK

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TREATING ENDOMETRIAL HYPERPLASIA

  • Endometrial Intraepithelial Neoplasia (EIN)
    • Definitive management ⇒ Hysterectomy + Bilateral Salpingo Oophorectomy*

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  • Hyperplasia without atypia
    • 1st line = Medical Management
      • Progesterone-based hormonal interventions
        • LNG-Ius, OCPs, Depo-Provera, Oral Progestins
          • If systemic treatment then need bx q3-6mo (SOGC 390)

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  • Lifestyle changes = Weight Loss
    • Exercise, Diet, Bariatric Surgery

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ESTROGEN vs. PROGESTERONE

  • Causes endometrium to proliferate
  • Causes breast stimulation (which can lead to breast cancer)
  • Increases body fat
  • Increases risk of endometrial cancer
  • Increases risk of gallbladder disease
  • Reduces vascular tone
  • Slightly restrains osteoclast function
  • Increases risk of blood clots
  • Maintains secretory endometrium
  • Protects against fibrocystic breast changes; may prevent breast cancer
  • Helps use fat for energy
  • Lowers risk of endometrial cancer
  • Restores vascular tone
  • Promotes osteoclast function and bone growth
  • Lowers risk of blood clots

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ESTROGEN

PROGESTERONE

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ENDOMETRIAL CANCER

  • Symptoms: PMB ranging from spotting to heavy prolonged bleeds
  • Most common gynecologic malignancy

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  • ~80% cases are in postmenopausal women (SOGC 249), avg age = 63 yo (Lu et al 2020)
  • 5 year survival
    • Overall=86%
    • Local=95%
    • Regional=67%
    • Metastases=23%

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ENDOMETRIAL HYPERPLASIA/CANCER RISK FACTORS

  • Menstrual factors
    • Early Menarche
    • Late Menopause
    • Anovulation
    • Nulliparity
    • Infertility
    • PCOS
  • Iatrogenic
    • Unopposed Exogenous Estrogen
    • Tamoxifen
  • Comorbidities
    • Age
    • Obesity
    • Diabetes
    • HTN
    • Genetics (e.g. Lynch, Cowden, Peutz-Jeghers)
  • Smoking
  • Progesterone based contraceptive use
  • History of induced abortion

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INCREASES RISK

DECREASES RISK

Biggest RF will be anything leading to excess/unregulated estrogen exposure

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OTHER CAUSES

  • Polyps
    • Endometrial overgrowths composed of stroma + glands + blood vessels
  • Prevalence in PMB = 13-50% (SOGC 249)
  • Histology ⇒
    • Benign (>75%)
    • Simple or complex Hyperplasia (10-15%)
    • Malignant (0.5-5%)
    • Tx: Hysteroscopic Resection

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CASE

PATHOLOGY SHOWS:

No Endometrial Hyperplasia or malignancy

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  • 59-Year-Old
  • Gravida(G): 3
  • Para (P): 2

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Presents to the office with self-reported 3 months of intermittent vaginal bleeding (spotting). Recently she has noticed some larger quantities and small clots.

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GENITOURINARY SYNDROME OF MENOPAUSE (GSM, VAGINAL ATROPHY)

  • Pathophys. ⇒ Estrogen Derication
    • Degeneration of vaginal wall connective tissue.
    • Vaginal Epithelium thinks & lowered Glycogen production

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  • Prevalence: ⇒ 27-55% (Johnstone et al)

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  • Symptoms: ⇒ Vaginal dryness, irritation, Dyspareunia, recurrent UTIs

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  • Treatment
    • Vaginal moisturizers (Replens)
    • Local Estrogen replacement (Premarin cream, Estagyn cream, Vagifem tabs, Imvexxy, Prasterone)

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OTHERS

  • Iatrogenic⇒ Medications that alter Hemostasis (Anticoag, AntiPLT)
  • Postmenopausal hormonal therapy (if Estrogen-Progesterone)
  • GU Malignancies (Leiomyosarcoma, Cervical, Vulvar)
  • Post-radiation therapy
  • Disease in adjacent organs
    • Diverticulitis can cause GUT inflammation
    • Fistulas
    • Colon Cancer
  • Infection
    • Genital Tuberculosis (rare)

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REFERENCES

  • Auclair, M.-H., Yong, P. J., Salvador, S., Thurston, J., Colgan, T. (T., & Sebastianelli, A. (2019). Guideline no. 390-classification and management of endometrial hyperplasia. Journal of Obstetrics and Gynaecology Canada, 41(12), 1789–1800. https://doi.org/10.1016/j.jogc.2019.03.025
  • The detection and management of vaginal atrophy. (2004). Journal of Obstetrics and Gynaecology Canada, 26(5), 516–518. https://doi.org/10.1016/s1701-2163(16)30664-8
  • Lu, K. H., & Broaddus, R. R. (2020). Endometrial cancer. New England Journal of Medicine, 383(21), 2053–2064. https://doi.org/10.1056/nejmra1514010
  • Namazov, A., Gemer, O., Ben-Arie, A., Israeli, O., Bart, O., Saphier, O., Mahler, N., Kapustian, V., & Silberstein, T. (2019). Endometrial polyp size and the risk of malignancy in asymptomatic postmenopausal women. Journal of Obstetrics and Gynaecology Canada, 41(7), 912–915. https://doi.org/10.1016/j.jogc.2018.07.019
  • Overview of the evaluation of the endometrium for malignant or premalignant disease. UpToDate. (n.d.). Retrieved March 7, 2023, from https://www.uptodate.com/contents/overview-of-the-evaluation-of-the-endometrium-for-malignant-or-premalignant-disease?search=postmenopausal+bleeding§ionRank=1&usage_type=default&anchor=H2796780088&source=machineLearning&selectedTitle=2~71&display_rank=2#H2796780088
  • Wolfman, W. (2018). No. 249-asymptomatic endometrial thickening. Journal of Obstetrics and Gynaecology Canada, 40(5). https://doi.org/10.1016/j.jogc.2018.03.005

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