Vaginal bleeding in the non-pregnant female

Normal menstrual cycle

• 28 days +- 7
• Mean duration of menstrual flow is 4 days with most bleeding in first 2
• Four phases
  • Menses (Days 1-4)
  • Follicular (Days 5-14)
    • Ovary matures an oocyte and granulosa cells produce oestrogen, which stimulate endometrium to proliferate and thicken
  • Ovulation (Day 14)
    • Rising oestrogen levels in follicular phase drives pituitary FSH/LH release (below critical level, oestrogen has negative feedback but then above critical level, stimulates release), which stimulates ovulation
  • Luteal
    • Corpus luteum is residual follicular capsule and produces oestrogen and progesterone to maintain the endometrial lining
    • Involutes in absence of hCG, leading oestrogen and progesterone levels to fall and menses to occur due to vasoconstriction of spiral arterioles

Menopause

• Mean age of 51
• As age increases, oestrogen levels fall and the pituitary produces continuously elevated levels of FSH and LH and there is a lack of midcycle rise in oestrogen to trigger surge of FSH/LH for ovulation to occur
• Oestrogen levels gradually fall to near zero as follicles become atretic

Definitions

• Abnormal vaginal bleeding – Any bleeding different to usual cycle
• Menorrhagia – Menses >7 days, >60mL or <21 days recurrence
• Metrorrhagia – Irregular bleeding outside of usual cycle
• Menometrorrhagia – Excessive irregular vaginal bleeding
• Dysfunctional uterine bleeding – Abnormal vaginal bleeding due to anovulation
• Postcoital bleeding – Vaginal bleeding after intercourse, suggestive of cervical bleeding
• Post-menopausal bleeding – any bleeding that occurs >6mo after cessation of menstruation

History

• Reproductive – Age of menarche, menstrual hx, LNMP, pattern, dysmenorrhoea
• Sexual hx – Current sexual activity, contraception, barrier, pregnant, GxPxTxMx, previous ectopic pregnancy, previous STI/PID
• Trauma
• Foreign body
• PMHx – Coagulopathy, diabetes, thyroid, liver, PCOS
• Associated symptoms – Urinary, GI, musculoskeletal, fever, syncope

Causes of bleeding by age

• Adolescent
• Anovulation, pregnancy, exogenous hormone use, coagulopathy
• Reproductive
• Pregnancy, anovulation, exogenous hormone use, uterine leiomyomas, cervical/ endometrial polyps, thyroid dysfunction
• Perimenopausal
• Anovulation, uterine leiomyomas, cervical and endometrial polyps, thyroid dysfunction
• Postmenopausal
• Endometrial lesions (30%)
• Exogenous hormone use (30%)
• Atrophic vaginitis (30%)
• Other tumor – vaginal, cervical, vulvar (10%)

Organic causes of bleeding

• Reproductive tract
• Pregnancy
• Leiomyomas
• Adenomyosis
• Endometriosis
• Neoplasia
• PID
• Systemic disease
• Coagulopathy
• Cirrhosis
• Exogenous hormone use
• Endocrinopathies
• Dysfunctional uterine bleeding (diagnosis of exclusion)
• Ovulatory or anovulatory

Leiomyomas (fibroids)

• Most common pelvic tumor
• 25% of white women and 50% of black women
• Usually multiple
• Decrease in size during menopause and increase early in pregnancy and with COCP use
• 30% of patients experience pelvic pain and abnormal bleeding
• Acute pain can occur with torsion or degeneration
• Degeneration typically due to rapid enlargement in early pregnancy and subsequent loss of blood supply and necrosis
• Presents with tenderness, rebound guarding, fever, leukocytosis
• Rapid growth at any age (when not pregnant) or after menopause is highly suggestive of malignant transformation
• Management
  • NSAID’s, progesterone and GRH agonists
  • Surgical removal has a 30% rate of recurrence and significant bleeding complications
  • Uterine artery embolisation may be helpful in reducing size and symptoms

Adenomyosis

• Endometrial gland development into the myometrium
• Dysmenorrhoea occurs just before or at time of menses
• Menorrhagia is common due to aberrant tissue impairing uterine contractility
• Therapy is symptomatic

Neoplasia

• Any malignancy can cause bleeding
• Endometrial hyperplasia or cancer MUST be considered in any woman with abnormal vaginal bleeding if >35 years old or younger with risk factors
• All patients with postmenopausal bleeding need referral for outpatient USS and endometrial biopsy

Systemic disorders

• Primary coagulation disorders account for 5-10% of menorrhagia in adolescents
• vWD is most common
• Hypothyroidism 0.3-2.5% incidence
• Cirrhosis may cause abnormal bleeding through impaired oestrogen metabolism

Dysfunctional uterine bleeding

• Diagnosis of exclusion after organic and systemic disorders ruled out
• Some texts refer to anovulatory cycles only as DUB

DUB – Ovulatory

• Regular periods that are preceded by breast tenderness, abdominal bloating and dysmenorrhoea
• Can occur due to low oestrogen levels
• Mostly adolescence or perimenopausal period
• Rx – Oral contraceptives, NSAID’s, progestins
• Endometrial ablation can be used for refractory cases and hysterectomy for those with excessive blood loss that fail medical therapy

DUB – Anovulatory

• Menorrhagia due to anovulatory DUB is seen in 10-15% of all gynaecology patients
• Common in perimenarchal, perimenopausal and those with endocrinopathies, PCOS, exogenous hormone use and liver/renal disease
• In adolescence is due to immature HPO axis
• Ix warranted if bleeding >9 days, recurs within 21 days or produces anaemia
• In perimenarchal age, progestins are preferred as COCP may impair maturation of HPO axis • In reproductive-age female:
• Usually irregular due to fluctuating oestrogen levels below critical level required for maintaining endometrial growth with relative progesterone deficiency
• Typically presents as amenorrhoea with periodic menorrhagia
• Rarely associated with cramping as lack progesterone-mediated myometrial contractions or spiral arteriolar vasoconstriction
• Increases risk of endometrial hyperplasia and adenocarcinoma

Treatment of ovulatory menorrhagia (Cameron)

• Progestins
  • Oral norethisterone 5mg BD/TDS
  • Oral medroxyprogesterone 10mg OD to TDS
  • On days 1-21 of a 28 day cycle
  • Reduces bleeding by 87%
  • Poor adherence to due to nausea, lethargy, headache, bloating and acne
• Tranexamic acid
  • 1g TDS for frst 3-4 days of each menstrual cycle
  • CI in active thromboembolic disease (although studies have shown NO EVIDENCE for increased risk of this
  • Reduces blood loss by 47%
• NSAID’s
  • 29% reduction in blood loss
  • Particularly helpful in dysmenorrhoea
  • Should be started on first day of period and continued until bleeding or pain cease
  • Mefenamic acid 500mg TDS, naproxen 250mg TDS or ibuprofen 400mg TDS
• COCP
  • Longer term therapy with COCP reduces blood loss by 43% if pill contains 35mcg of ethinyloestradiol

Treatment of anovulatory bleeding

• Underlying pathology is relative progesterone deficiency (as if not ovulating, not forming corpus luteum) so must remedy this +- tranexamic acid/NSAID
• Progestin
• Medroxyprogesterone 20mg PO TDS for one week then reduce to 20mg daily for 3 weeks
• Norethisterone 5mg PO TDS for 12 days
• Once progestin treatment stops, will have withdrawal bleed in 3-10 days (must warn women of this)
• For subsequent cycles recommend medroxyprogesterone 10mg PO daily or norethisterone 5mg PO daily on days 12-25 of each cycle
• Tranexamic acid or NSAID’s as for ovulatory cycles
• COCP
• Can start monophasic COCP with at least 30mcg ethinyloestradiol

Patients with PCOS

• Classic triad: Obesity, hirsutism, oligomenorrhoea
• Menses, when it does occur, is heavy and prolonged
• Also get acne, androgen-dependent alopecia, elevated serum androgens, hyperinsulinaemia and hypersecretion of LH with normal or low FSH
• Typical ovarian morphology is not necessary for diagnosis and may in fact be a response to anovulatory cycles

UpToDate – Non-pregnant reproductive age women

• Most common causes of abnormal uterine bleeding
  • Structural pathology – Fibroids, polyps, adenomyosis
  • Ovulatory dysfunction
  • Disorders of haemostasis
  • Neoplasia
  • PALM-COEIN classification system has replaced old menorrhagia/metrorrhagia/oligomenorrhoea
  • Polyp
  • Adenomyosis
  • Leiomyoma
  • Malignancy and hyperplasia
  • Coagulopathy
  • Ovulatory dysfunction
  • Endometritis
  • Iatrogenic
  • Not yet classified

• Most common causes of cyclical heavy menstrual bleeding (ovulatory)
  • Uterine leiomyomas
  • Adenomyosis
  • Caesarian scar defect
  • Bleeding disorder
  • Other causes
  • Endometrial hyperplasia
  • Copper IUD
  • Endometrial polyps, endometritis or PID

• Most common causes of intermenstrual bleeding
  • Endometrial polyps
  • Contraceptive
  • Endometrial hyperplasia/carcinoma
  • Endometritis/PID
  • Caesarean scar defect
  • Cervical pathology

• Irregular bleeding (Ovulatory dysfunction)
  • May be anovulatory or oligo-ovulatory
  • Typically no bleeding for months then spotting/heavy bleeding
  • Molimina absent (symptoms around menstruation)
  • More likely perimenarchal and perimenopausal
  • PCOS, thyroid, hyperprolactinaemia

• Endometrial sampling
  • Age 45 to menopause
    • Any abnormal uterine bleeding
  • <45yo
    • Persistent AUB
    • History of unopposed oestrogen (obesity, chronic anovulatory cycles)
    • Failed medical management
    • Tamoxifen therapy
    • Lynch syndrome

• Heavy menstrual bleeding – Treat if affecting quality of life or causing anaemia
  • Find and treat cause
  • Medical first-line: COCP, high-dose oral progestin, NSAID, TXA
  • Intermenstrual bleeding – Find cause e.g. polyp
  • Ovulatory dysfunction
  • COCP
  • High-dose oral progestin
  • NSAID
  • TXA
  • Decision on treatment should consider dysmenorrhoea, contraception requirements, elevated VTE risk, migraine with aura and HTN

Last Updated on September 29, 2021 by Andrew Crofton