ObGyn E1.5 - Amenorrhea

Steps in evaluating primary amenorrhea (flowchart)

1) b-hCG 2) PE for secondary sex characteristics 3) Serum FSH 4) US to determine presence or absence of uterus.

Danazol

Androgenic steroid 200 to 400 mg/day Expense and side effects limit use.

Polymenorrhea

Frequent bleeding (every 21 days or less)

Menometrorrhagia

Frequent bleeding that is excessive in amount and duration.

What do GnRH agonists do to premenopausal women?

Induces a menopausal state in premenopausal women that leads to amenorrhea.

Estrogen-progestin contraceptives options

OCs with 30 to 35 mcg ethinyl estradiol are most effective. May be prescribed in a cyclic (with a monthly withdrawal bleed) or continuous (no withdrawal bleed) regimen. CONTRAINDICATED if at risk for thrombosis.

Ovarian Dysfunction

Ovarian follicles are either "worn out" or resistant to stimulation by FSH and LH. *Causes:* Chromosomal (Turner's syndrome) Immunologic (Blizzard's syndrome) Iatrogenic (chemotherapy or menopause) Unknown (premature natural menopause) *Effect on menstruation:* Estrogen deficiency = no endometrial lining. *Symptoms:* Related to low estrogen (like menopause, see chart).

Oligomenorrhea

Reduction of the frequency of menses (interval > 35 days but < 6 months)

Hypothalamic-pituitary dysfunction

*Causes:* Usually functional (weight loss/gain, excessive exercise, etc.) Drug-induced (marijuana, tranquilizer use) Neoplasms (pituitary) Psychogenic Head injury Chronic medical illness *Effect on menstruation:* GnRH decreased = all other hormones decreased. No formation of uterine lining or ovulation/menstruation. *Symptoms:* Only amenorrhea - cannot distinguish from outflow obstruction from history alone.

Anovulation (causes and treatment)

*Causes:* Polycystic ovarian syndrome (PCOS), hypothalamic or pituitary origin. *Treatment:* OCPs.

Treatment of Anovulatory Uterine Bleeding

*Medical Treatment:* Oral Progesterone Estrogen-progestin contraceptives Levonorgestrel IUD (Merena) NSAIDs Antifibrinolytic agents GnRH agonists Danazol

Amenorrea

absence of menstruation

Progestin challenge test

*Administer either 100 mg progesterone inj or 5-14 day course of oral medroxyprogesterone.* In a normal uterus, progesterone converts the proliferative endometrium into a secretory endometrium. *If a withdrawal bleed occurs:* patient has functional outflow tract and normal estrogen levels. Problem is anovluatory or oligoovulatory. *If a withdrawal bleed does NOT occur:* Either hypoestrogenic state (perimenopause vs. ovarian failure) vs. anatomic cause (Asherman's syndrome vs. OT obstruction). *Must perform estrogen-progestin challenge test.*

Obstruction of Genital Outflow Tract

*Causes:* Most common in primary amenorrhea: *Mullerian agenesis.* Can also have complete absence of uterus/vagina or imperforate hymen. Most common cause in secondary amenorrhea: *Asherman syndrome* from scarring of uterine cavity. *Effect on menstruation:* Prevents bleeding even if ovulation occurs. *Symptoms:* None, just amenorrhea.

Surgical treatment options for anovulatory uterine bleeding

*Endometrial ablation* - minimally invasive, and as effective as the LNG-IUD. However, pregnancy is contraindicated after this procedure! *Hysterectomy* - definitive treatment.

What are the causes of abnormal uterine bleeding?

*Most common = anovulatory uterine bleeding.* Others: Pregnancy Structural uterine pathology (eg, fibroids, polyps, adenomyosis) Disorder of hemostasis Neoplasia

Asherman syndrome

*Most frequent anatomic (outflow obstruction) cause of secondary amenorrhea.* Scarring of uterine cavity. Risks: D&C or previous infection of uterine cavity. Treatment: Surgical lysis of adhesions for mild cases.

Most common etiologies of secondary amenorrhea

*Pregnancy is #1* Ovarian disease — 40% Hypothalamic dysfunction — 35% Pituitary disease — 19% Uterine disease — 5% Other — 1%

What is the most common cause of secondary amenorrhea? Associated symptoms?

*Pregnancy!* Symptoms: Breast tenderness, weight gain, nausea (w/ possible hypersensitivity to smells)

Characteristics of abnormal uterine bleeding

- Passage of large clots (dime sized clots are common and normal) - Duration > 7 days - Flow greater than 80 mL/cycle (i.e. more than 6 full pads or super-sized tampons per day) - Occurring more frequently than every 21 days or less frequently than every 35 days - Intermenstrual bleeding or postcoital spotting

Evaluation of secondary amenorrhea (flowchart)

1) B-hCG 2) serum TSH and prolactin

Most common etiologies of primary amenorrhea

1) Chromosomal w/ gonadal dysgenesis - 50% 2) Hypothalamic hypogonadism - 20% 3) Mullerian agenesis - 15% 4) Transverse vaginal septum or imperforate hymen - 5% 5) Pituitary disease - 5%

Evaluation of abnormal uterine bleeding

1) FIRST r/o anatomic cause (fibroids, cervical/vaginal lesions, bleeding from other sites) 2) Basal body temp chart 3) Endometrial biopsy

Management of PCOS

1) Lifestyle changes to reduce weight and DM2 2) *Spironolactone* 50-100 mg BID or topical cream for hirutism. 3) *OCPs* for women NOT wanting pregnancy. 4) *Clomid* to induce ovulation for pregnancy.

Primary amenorrhea

1) Never menstruated by age 13 and w/o secondary sexual development OR 2) Never menstruated by age 15 but with secondary sexual development.

Causes of amenorrhea

1) Pregnancy 2) Hypothalamic-pituitary dysfunction 3) Ovarian dysfunction 4) Alteration of the genital outflow tract

Levonorgestrel-IUD (Mirena)

High local progestin concentration causes thinning of the endometrium. Some may stop periods entirely, other will make them 90% lighter. IUD inserted in-office. Oral/parenteral progestins are less effective. Doesn't affect fertility down the road, but good option for someone that doesn't desire fertility in the near future.

Metrorrhagia

Irregular bleeding or bleeding between periods

Oral progesterone options

Medroxyprogesterone acetate (Provera) - 10mg/day for first 10-12 days of month Micronized oral progesterone (Prometrium oral) - 200mg/ day for first 12 days of month

What is Anovulatory Uterine Bleeding (aka dysfunctional uterine bleeding)?

Most common cause of abnormal uterine bleeding. Caused by *infrequent ovulation and chronic exposure to estrogen.* Proliferative endometrium is never converted to secretory endometrium (absence of ovulation & low progesterone) and outgrows its blood supply, sloughing irregularly. *Risks:* Incapacitating blood loss Endometrial hyperplasia and/or carcinoma (from chronic estrogen exposure)

What is Polycystic Ovarian Syndrome (PCOS)?

One of the most common endocrine/metabolic disorders of women. *Symptoms:* Menstrual irregularity (oligo or anovulation). Evidence of hyperandrogenism (hirsutism, acne, male pattern balding) + high serum androgen concentration. Usually overweight w/ DM2. Difficulty conceiving. *80-100% will have polycystic ovaries on US, however it is NOT required for diagnosis!*

Secondary amenorrhea

Previously menstruated but has failed to menstruate for >3 cycles or for 6 months.

Menorrhagia

Prolonged or excessive uterine bleeding that occurs at *regular intervals* (loss of ≥ 80mL; lasts > 7 days).

NSAIDs and anovulatory uterine bleeding

Reduce the volume of menstrual blood loss by 20-50%. Also reduces the rate of prostaglandin (PGE2 and PGF2 alpha) synthesis in the endometrium, leading to vasoconstriction and reduced bleeding. *Directions:* Start on the first day of menses and discontinue after 5 days or at the end of menses. *Options:* Naproxen 500 mg at onset and 3-5 hours later, then 250 to 500 mg BID Ibuprofen 600 mg PO daily

Antifibrinolytic agents

Tranexamic acid 1gm 3-4x/ day during menses for up to 5 days. Only taken on the days of menses; does not interfere with fertility.

What is the most common cause of gonadal dysgenesis (primary amenorrhea)?

Turner's syndrome - order karyotype to confirm.

Estrogen-Progestin Challenge Test

Used to differentiate between hypoestrogenic state (ovarian failure) vs. outflow obstruction (likely Asherman's). *1) Give estrogen* Premarin 1.25 mg PO x 21 days or estradiol 2 mg PO x 21 days *2) Then give progesterone x 7-10 days.* Anticipate bleeding within 7 days. See flowchart.

A 33-year-old female presents with c/o having stopped menstruating 8 months ago following a spontaneous abortion. She had a D&C at that time. She has no significant medical or surgical history. She experienced menarche at age 11 years and notes that menses have been regular at 28-31 day intervals until recently. Pregnancy test is negative. No abnormality is found on physical exam. Based on this, what is the most likely diagnosis? A. Premature menopause B. Mullerian dysgenesis C. Asherman's syndrome D. Ectopic pregnancy

C. Asherman's syndrome - outflow obstruction (no lining building up as a result of the D&C).

Which of the following bleeding patterns is considered abnormal? A. Passage of dime sized clots B. Bleeding lasting longer than 5 days C. Bleeding more frequently than every 21 days D. Flow greater than 60 mL per cycle

C. Bleeding more frequently than every 21 days (or longer than 35).