Dysfunctional Uterine Bleeding and Anovulation - Labarre Flashcards
Menses Phase
day 0-end of cycle around day 8
Proliferative Phase/Follicular Phase
day 8-14
Predominance of estrogen over progesterone and a build up of endometrium (prepping for implantation)
(Follicular – follicles growing and oocytes maturing)
Secretory Phase/Luteal Phase
day 14
Begins after ovulation triggers progesterone production
Marked by a reaction to the combination of estrogen and progesterone and stabilization in the thickness of the endometrium (ready for embryo)
(Luteal –LH transforming oocyte to corpus luteum)
Normal Menstrual Cycle
Hypothalamus secretes GnRH, stimulating the pituitary to secrete FSH/LH
FSH acts on the ovary to increase Estradiol and stimulate follicles which has negative feedback on FSH
LH also causes increase in Estradiol but there is positive feedback on the LH resulting in LH surge
LH surge increases estrogen resulting in ovulation within 48 hours
After ovulation -Follicle becomes corpus luteum - secretes progesterone.
Progesterone stabilizes the endometrium to prepare for fertilized egg
If no fertilization –corpus luteum regresses and progesterone drops resulting in unstable lining and menses.
If fertilized egg implants- hCG is secreted with acts like LH and maintains progresterone which in turn stabilizes the endometrium
Primary Amenorrhea
no spontaneous uterine bleeding by age 15 in the presence of normal sexual characteristics
- OR -
by age 13 in the absence of any secondary sexual characteristics
Secondary Amenorrhea
the absence of menstrual bleeding for >3 months in women with previously normal menses, or >6 months in women with irregular menses
General causes of Primary Amenorrhea
Gonadal dysgenesis- 43% (Turner syndrome)
Mullerian Agenesis – 15% (absence of vagina or uterus)
Physiological delay of puberty -14% (systemic illness)
PCOS -7%
GnRH deficiency – 5%
Transverse Vaginal Septum – 3%
Hypopituitarism- 2%
Anorexia/wt loss -2%
Causes of Secondary Amenorrhea
Adult Onset:
Hypothalamus- 35%
Pituitary – 17% (hyperprolactinemia, empty sella, sheehan syndrome, cushings syndrome)
Ovary - 40% (PCOS, primary ovarian insufficiency)
Uterus – 7% (uterine adhesions)
Other – 1 % (adrenal hyperplasia, ovarian and adrenal tumors, hypothyroidism)
Adolescent onset: Hypoandrogenism – from PCOS- 50%
disorders of outflow tract causing amenorrhea
Imperforate hymen (Cyclic pelvic pain/Primary Amenorrhea)
Transverse Vaginal Septum (similar to imperforate hymen)
Mullerian Agenesis (vaginal agenesis): Mayer-Rokitansky-Kuster-Hauser (MRKH) Syndrome, Associated with uterine agenesis or rudimentary uterus
Androgen Insensitivity Syndrome- 46 XY
Ashermans Syndrome (Intrauterine scar tissue/adhesions, Typically due to uterine trauma, surgical procedure (D&C, Ablation) or severe infection)
disorders of the ovary causing amenorrhea
Gonadal Dysgenesis/Agenesis – Chromosomal Abnormalities:
Turner Syndrome (45 XO): depletion of oocytes and follicles, Reduced negative feedback on FSH from Estradiol
46 XX Gonadal Dysgenesis: Primary Ovarian Insufficiency (clinical Menopause before 40), Secondary to Chemo, Radiation, Autoimmune
46 XY Gonadal Dysgenesis: Resistance to Testosterone due to androgen receptor defect, External genitalia typically female, Decreased anti-mullerian Hormone- Ovarian failure
PCOS (more later)
17 Alpha-Hydroxylase Deficiency: Decreased cortisol synthesis, overproduction of ACTH
disorders of the anterior pituitary causing amenorrhea
Pituitary adenoma- Hyperprolactinemia: Prolactin inhibits GnRH (so decrease in LH/FSH), Common cause of seconary amenorrhea, Rare cause of primary amenorrhea
Other Sellar Masses –cysts, meningiomas etc
Sheehan syndrome: Necrosis of pituitary- post partum or trauma
Damage to pituitary: Radiation, (infiltrative) hemochromatosis, sarcoidosis, lymphocytic hypophysitis, Medications – opiates, phenothiazines- can increase prolactin
Thyroid disease: Hypothyroid increases TSH which suppresses GnRH
disorders of CNS or hypothalamus
Functional Hypothalamic amenorrhea
Abnormal GnRH secretion –decreased LH surges, no follicular development, low estradiol; Eating disorders, Exercise, Stress –increases cortisol and decreases FSH/LH
Isolated GnRH deficiency (Idiopathic hypogonadotropic hypogonadism)
Kallmann Syndrome –genetic
Tumors
Systemic Illness: resulting in decrease in GnRH secretion –Celiac, Type 1 DM, IBS, JRA, Syphillis, TB
Hx in evaluation of Amenorrhea
Menstrual history: Age of onset of menses, previous pattern
Reproductive history: Use of BCP’s, previous OB/GYN procedures, development (hair growth/acne), pregnancy, weight changes, menarche, menopause
General medical history: Endocrine/metabolic disorders, medications, illnesses, infections,
Medications: Marijuana – estrogenic activity, antipsychotic meds increase prolactin, cytotoxic drugs like Chemotherapy
Family history- sister/mother
Social history: Med student?, marathon runner? Nutritional or emotional stressors?
Physical exam in evaluation of Amenorrhea
Look for abnormal anatomy
Genital Development
BMI
Hair distribution
Gallactorrhea
Signs of Androgen excess, estrogen deficiency or estrogen excess
Diagnostic tests in evaluation of Amenorrhea
Labs: hCG – RULE OUT PREGNANCY!, Prolactin, FSH, TSH, CBC, Von Willebrand, PTT, INR, LFT, renal
If patient shows signs of hypogonadism on exam
add Total testosterone, 17-hydroxyprogesterone and DHEA-S
Pap smear
STD screening
Pelvic US, Consider MRI/CT – evaluate pituitary if concerned
Determine Relative Estrogen Status: Progesterone withdrawal test (use methylprogesterone)
Tx of Amenorrhea
Need to have clear diagnosis first!!!
Hypothyroid– thyroid replacement
Ovarian Failure– estrogen replacement
Pituitary Tumor–medication or surgery
Hypothalamic Amenorrhea–change lifestyle, cyclical hormones
Risks with untreated Amenorrhea
Hypothalamic => Risk of decreased bone density
Anovulation => Risk of Endometrial cancer
Menorrhagia
Normal intervals, but prolonged (>7d) or excessive (>80 ml/cycle)
Metrorrhagia
irregular and more frequent intervals, amount is variable
Menometrorrhagia
prolonged or variable amounts occurring irregularly and more frequently than normal
PALM COEIN
PALM: structural causes
Polyp
Adenomyosis
Leiomyoma (affecting submucosa, not affecting endometrial cavity)
Malignancy and hyperplasia
Other structural lesions- scar, AV malformation, foreign body etc.
COEIN: Non-structural Causes
Coagulopathy
Ovulatory Dysfunction (see additional slides)
Endometrial (hyperplasia/carcinoma, sarcoma, infection, inflammation, PID)
Iatrogenic (medications -anticoagulants, hormones, IUD)
Not yet classified
Official Nomenclature for Abnormal Uterine Bleeding
PALM-COEIN SYSTEM:
Abnormal Uterine Bleeding + Use descriptive term (Heavy Menstrual bleeing/Intermenstrual Bleeding) + Paired with Etiology or etiologies
Non-Structural Causes of abnormal Bleeding
Pregnancy! (not part of Palm –Coeins): Ectopic pregnacy
Miscarriage, Placenta previa, Gestational trophoblastic disease
Medications: Steroids, thyroid, hormones, anticoagulants, SSRIs, herbs (ginko, ginseng, soy), IUD, Hormones
Systemic diseases (ovulatory or anovulatory): Adrenal changes, hepatic disease, PCOS, pituitary adenoma, Renal, Thyroid
Ovulatory Bleeding
Bleeding cyclic – regular intervals every 24-35 days
Increased rate of blood loss resulting from vasodilation of vessels
Abnormal Ovulatory Bleeding
Physical lesion – polyp, fibroid adenomyosis
Decreased tone possibly related to prostaglandins
Infection
Bleeding disorder: Factor deficiency, Leukemia, Platelet disorder, Von willebrand disease
Ovulatary Dysfunction
Anovulation or oligo-ovulation
Typically alternating between missed menses and heavy menses –Variable flow and durations
Irregular bleeding- more unpredictable
Disturbance of the normal Hypothalamic-pituitary-ovarian axis
Progesterone deficient/estrogen dominant state
More common in extremes of reproductive years (menarch, menopause)
Conditions that Affect Ovulation
PCOS – most common – affects 6% of women
Thyroid
Estrogen producing tumors
Liver and kidney disease
Diabetes (esp uncontrolled)
Medications: Estrogens/progestins, Steroids, Antiepileptics
(Especially valproic acid), Antipsychotics
Any of the conditions that affect Pituitary or hypothalamic function previously listed under amenorrhea
No ovulation, therefore no corpus luteum – resulting in:
Decreased progesterone
Prolonged estrogen stimulation
Excessive proliferation
Endometrial instability
Erratic bleeding
***Increases risk of endometrial hyperplasia and cancer
PCOS
Infrequent or no ovulation – irregular menstration
Signs of hyperandrogenism: Acne, Hirsutism, Male pattern hair loss
Elevated serum androgen concentration (DHEA-S or Testosterone)
Polycystic ovaries on US (at least 1 ovary with 12 or more follicles measuring 2-9mm and increased ovarian volume)
Who Needs Evaluation for abnormal bleeding?
Adolescents: Consistently more than 3 months between cycles or Irregular cycles for more than 3 years
Adult Women: Suspected recurrent anovulatory cycles
Perimenopausal: Increased volume or duration of bleeding over baseline, Periods more often than every 21 days, Intermenstrual spotting, Postcoital bleeding
Risks for Endometrial Cancer
Obesity
Nuliparity
Previous tamoxifen therapy
Unopposed estrogen therapy
Diabetes
Increased with age:
Who warrants Endometrial Biopsy?
Adolescents: Obese with 2-3 years of untreated anovulatory bleeding
Women 6 months), Diabetes, Obesity, Use of tamoxifen, Lynch or Cowden Syndrome, PCOS, Not responding to medical management of abnormal bleeding
Women >45: Ovulatory dysfucntion; Cycle
