Lecture 6 Menstruation Disorders - Women's Health

Normal Puberty

Endocrine process that involves the physical, emotional, and sexual maturation

HPG Axis

1. Functions during fetal life through first few weeks then slows down to NF loop of estrogen

2. Reactivates during puberty

Estradiol causes

1. Breast production

2. Growth acceleration

3. Skeletal growth

4. Menstrual cycles

Sexual Maturation Sequence

1. Accelerated growth & ovarian enlargement

2. Thelarche

3. Pubarche

4. Maximum growth aka Growth spurt

5. Menarche

6. Ovulation

Fat Tissue and Onset of Puberty

Excess body fat can lead to early menarche

What other factors influence timing and progression of puberty?

1. BMI

2. socioeconomic conditions

3. Nutrition

4. Access to preventive healthcare

Thelarchy

1. Breast development

2. Most common earliest detectable secondary sex characteristic on PE

Pubarche

Public hair development

Menarche

Start of menses

Tanner Stages

1. Sexual maturity rating

2. Descriptions of development of secondary sex characteristics

Primary Amenorrhea

Absence of menses at age 15yo in the presence of normal growth and secondary sexual characterists

Secondary Amenorrhea

Absence of menses for more than 3 cycles in persons with regular cycles or 6mo with irregular cycles

Etiology of Primary Amenorrhea

1. Gonadal Dysgenesis (Turner Syndrome) 43%

2. Mullerian agenesis (absence of vagina and/or uterus) 15%

3. Physiologic delay of puberty (often genetic) 14%

4. Polycystic OVarian Syndrome 7%

Other Causes of Primary Amenorrhea

1. GnRH secretion deficiency

2. Weight loss

3. Transverse vaginal septum

4. Hypopituitarism

5. Imperforate hymen

6. Prolactinoma

Gonadal Dysgenesis - Primary Amenorrhea

1. Ovaries don't develop properly during prenatal development

2. Leads to various reproductive and hormonal issues

Mullerian Agenesis - Primary Amenorrhea

Congenital - uterine and upper vaginal structures fail to develop fully

Etiology of Secondary Amenorrhea

1. Pregnancy (MC)

2. Hypothalamic dysfunction

3. Pituitary disease

4. Thyroid disease

5. Ovarian Disorders

6. Uterine adhesions (Asherman Syndrome)

Hypothalamic Dysfunction - Secondary Amenorrhea

1. Functional hypothalamic dysfunction - decrease in GnRH secretion

2. Drug induced (weed, opiates, psychoactive drugs)

3. Hypothalamic tumors -> decrease GnRH

4. Chronic disease - T1DM, Celiac disease

What can cause functional hypothalamic dysfunction?

1. Weight loss

2. Excessive exercise

3. Nutritional deficiencies

4. Obesity

Pituitary Diseases that Cause Secondary Amenorrhea

Prolactinomas/hyperprolactinemia - presence of galactorrhea

Ovarian Disorders that Cause Secondary Amenorrhea

1. PCOS

2. POI - depletion of ovarian reserve before 40 y/o (FSH/LH rises, estradiol levels drop)

3. Ovarian tumors

History for Secondary Amenorrhea

1. Stress, weight, diet, exercise, eating disorder

2. Drugs

3. Hirsutism, acne, irregular periods

4. Galactorrhea

5. HA, visual field defects, fatigue, polydipsia, polyuria

6. Hot flashes, vaginal dryness, poor sleep, decrease libido

7. Hx of D&C, endometriosis, infection leading to scarring

Stress, weight, diet, exercise, eating disorder (Secondary Amenorrhea - Hx)

Functional hypothalamic amenorrhea

Drugs (Secondary Amenorrhea - Hx)

1. OCP

2. High dose progestin

3. Danazol

4. Metoclopramide

5. Antipsychotic drugs

6. chronic opiate use

7. Marijuana

Hirsutism, Acne, Irregular Periods (Secondary Amenorrhea - Hx)

Polycystic ovaries

Galactorrhea (Secondary Amenorrhea - Hx)

Hyperprolactinemia

HA, Visual Field Defects, Fatigue, Polydipsia, Polyuria (Secondary Amenorrhea - Hx)

Sellar masses

Hot Flashes, Vaginal Dryness, Poor Sleep, Decreased Libido (Secondary Amenorrhea - Hx)

Primary Ovarian Insufficiency (POI)

Hx of D&C, Endometriosis, Infection Leading to Scarring (Secondary Amenorrhea - Hx)

Asherman Syndrome

Secondary Amenorrhea PE

1. BMI

2. Vulvovaginal exam/ genital tract anatomy

3. Neuro exam - visual field defects, if indicated sign of pituitary mass/prolactinoma

4. Hirsutism, acne, alopecia - signs of hyperandrogenism

5. Nipple discharge

Imaging Studies for Secondary Amenorrhea

1. Pelvic ultrasound

2. MRI or CT depending on history

Laboratory Tests for Secondary Amenorrhea

1. Pregnancy test - serum HCG

2. Complete labs on day 3 if menses occur

3. TSH to r/o thyroid disease

4. Serum prolactin (PRL) to r/o hyperprolactinemia

5. FSH to evaluate hypothalamic-pituitary axis

6. E2 (estradiol) to evaluate the pituitary-ovarian axis

7. If signs of hyperandrogenism, then order testosterone

Abnormal TSH (Secondary Amenorrhea )

Thyroid disease

Elevated Prolactin (Secondary Amenorrhea)

Hyperprolactinemia, r/o prolactinoma

Elevated FSH with low E2 (Secondary Amenorrhea)

POI (repeat FSH to confirm)

Low to Normal FSH, Normal E2 (Secondary Amenorrhea)

PCOS, intrauterine adhesions

Low to Normal FSH, with low E2 (Secondary Amenorrhea)

1. HPA disorder/Secondary Hypogonadotropic hypogonadism

2. Consider pituitary MRi

Elevated testosterone (Secondary Amenorrhea)

Likely PCOS

Secondary Amenorrhea - Progesterone Challenge Test

1. Helps to evaluate the integrity of the endometrial lining

2. Consider in patient with normal labs and history of uterine instrumentation

What does the Progesterone Challenge Test determine?

1. Adequate estrogen

2. competent endometrium

3. patent outflow tract

Progesterone Challenge Test

1. Medroxyprogesterone 10mg PO x 10-14 days

2. Should induce withdrawal bleeding upon completion

3. If no bleeding, GYN referral

If no withdrawal bleeding with Progesterone Challenge Test, ?

1. Consider estrogen-progesterone withdrawal test (determines if hypoestrogenic)

2. R/O uterine adhesions

Goals of Secondary Amenorrhea Tx

1. Tx underlying pathology

2. Achieve fertility

3. Prevent complications of disease

Functional Hypothalamic Dysfunction Tx

1. Lifestyle changes

2. CBT

Hyperprolocatinemia Tx

1. Cabergoline

2. Dopamine-agonist which will suppress prolactin and shrink tumor

Primary Ovarian Insufficiency Tx

HRT to reduce risk of osteoporosis and CVD

Hypogonadotropic Hypogonadism Tx

1. Pulsatile GnRH or human menopausal gonadotropins

2. Will tx infertility and hormone deficiencies

Intrauterine adhesions Tx

Hysteroscopic lysis of adhesions followed with course of estrogen to stimulate regrowth of endometrial tissue

PCOS tx

1. Lifestyle changes

2. OCP

3. Spironolactone (antiandrogen)

4. Metformin

5. Letrozole or clomiphene citrate to induce ovulation

Thyroid Disease tx

Manage appropriately

AUB

Uterine bleeding or abnormal quantity, duration or schedule

Epidemiology of AUB

Reproductive-age females

Etiology of AUB

1. PALM

2. COEIN

PALM Etiology of AUB

1. Polyp

2. Adenomyosis

3. Leiomyoma/fibroid

4. Malignancy/hyperplasia

COEIN Etiology of AUB

1. Coagulopathy

2. Ovulatory dysfxn

3. Endometrial

4. Iatrogenic

5. Not classified

PE for AUB

1. Assess hemodynamic stability

2. Assess for systemic illness

3. Assess for signs of hyperandrogenism, acanthosis nigricans, galactorrhea

Pelvic Exam for AUB

1. Confirm bleeding site

2. Size and contour of uterus

3. Adnexal mass and/or tenderness

Labs for AUB

1. Urine HCG with possible serum HCG

2. CBC

3. Ferritin

4. +/- (TSH, PRL, FSH, E2, testosterone, NAAT chlamydia, PT, aPTT)

Do you assess cervical cancer screening for AUB?

Yes

Imaging for AUB

Pelvic US, r/o mass, and assess endometrial thickness

Procedures for AUB

1. Endometrial biopsy to r/o endometrial cancer

2. >45 to menopause (frequent, heavy, prolonged, intermenstrual bleeding)

3. < 45 (persistent bleeding for 6mo or more)

AUB Management

1. May send to ED

2. Tx underlying dz

3. Refer to GYN for further evaluation and tx if necessary

AUB Management When No Clear Etiology

1. Combined E-P contraceptives or IUD (LNG 52mg or oral progestins; use nsaids or transexamic acid

2. If trying to conceive, combined OCPs or cyclic progestin therapy (can delay conception by mnths)

Fibroids Tx - AUB Management

Medical or surgical therapy

Endometrial Polyps Tx - AUB Management

Hysteroscopic polypectomy

Adenomyosis Tx - AUB Management

Medical or surgical therapy, including hysterectomy

Coagulopathy Tx - AUB Management

Tx underlying disorder

Management of Acute Heavy Bleeding Episodes

1. Evaluate and r.o organic pathology

2. Focus on controlling the acute bleeding epi & prevent future recurrences

Options to Prevent Future Recurrences of Acute Heavy Bleeding Episodes

1. IUD

2. OCPs

3. Progestin therapy (oral or IM)

4. Tranexamic acid

5. NSAIDs

If options fail or pt is hemodynamically unstable (Acute Heavy Bleeding Episodes)

1. Surgical mgt with D&C

2. Uterine artery embolization

3. Endometrial ablation

4. Hysterectomy

Options for Acute Heavy Bleeding Episodes

1. high dose controlled OCP (subsides in 48hrs)

2. high dose oral estrogen (if waiting 48hrs is unacceptable)

3. Progesterone (if anovulation)

4. Tranexamic acid (antifibrinolytic agent)

high Dose COC for Acute Heavy Bleeding

1. Tapering regimen

2. Five pills on day 1

3. Four pills on day 2

4. Three pills on day 3

5. Two pill on day 4

6. One pill on day 5

High dose oral estrogen for Acute Heavy Bleeding

1. Equine estrogen 2.5 mg every 6hrs

2. Decrease to BID when bleeding subsides

3. Continue x 21-25 days

Progesterone for Acute Heavy Bleeding

Medroxygprogesterone acetate 10-20mg TID x5-10days

Tranexamic Acid for Acute Heavy Bleeding

1. PT without high-risk thrombosis who fail other options or decline or should not use hormonal tx

2. 650 mg tablets: 1.3g 3 times daily for up to 5 days

Premenstrual syndrome (PMS)

The presence of physical and/or behavioral symptoms that occur repetitively in the second half (luteal phase) of the menstrual cycle and interferes with functioning

PMS Information

1. Cyclic, resolves shortly after menses onset

2. Affects 5-10% of women

3. 1-4 behavioral and/or physical symptoms

Behavioral Sxs of PMS

1. Mood swings (MC)

2. Anxiety, irritability

3. Sadness

4. Food cravings

5. Diminished interest in activities

6. Sensitivity to rejection

Physical Sxs of PMS

1. Bloating, fatigue (MC)

2. Breast tenderness

3. HA

4. Hot flashes

5. Dizziness

Premenstrual Dysphoric Disorder (PMDD)

1. DSM-5 - a severe form of PMS where anger, irritability, and internal tension are prominent

2. Affects 3-5% of women

PMS & PMDD Eval

1. Menstrual diary

2. Diagnosis tests (CBC, TSH)

PMS & PMDD Tx (Mild Sxs)

1. Lifestyle interventions - stress reduction, exercise

2. Supplements - Chasteberry

PMS & PMDD Tx (Moderate to Severe)

1. Combined OCP (monophasic)

2. SSRI (continuous, luteal phase only, sxs onset)

Most studied SSRIs for PMS/PMDD

Sertraline, citalopram, escitalopram, fluoxetine

Menstrual Diary for PMS/PMDD

1. For 2 or more cycles

2. Demonstrate cyclic nature of sxs specific to luteal phase

3. 1-4 sxs that interfere with functioning (PMS)

4. Must have 5/11 with 1 core/affective sxs (PMDD)

5. Symptom-free follicular phase

Dysmenorrhea

painful menstruation that inhibits normal activities

Primary Dysmenorrhea

1. Excessive in prostaglandins (PG E2 & F2-alpha) -> painful uterine muscle activity

When does primary dysmenorrhea begin?

Begins in adolescence after menstruation cycles are established

Secondary Dysmenorrhea

Underlying etiology identified

Causes of Secondary Dysmenorrhea

1. Endometriosis

2. Fibroids

3. Adenomyosis

4. ovarian cysts

5. PID

6. Pelvic adhesions

7. Cervical stenosis

8. IUD

9. IBD

10. IBS

11. Psychogenic disorders

When does secondary dysmenorrhea occur?

Later in life, secondary to an underlying cause

Primary Dysmenorrhea Clinical Presentation

1. Mth to mth recurrence

2. Spasmodic lower abdominal pain first 1-3 dys of menses

3. Suprapubic pain radiating to the back

4. N/V/D/HA

5. Dyspareunia NOT present

6. Tends to improve with advancing age

Secondary Dysmenorrhea Clinical Presentation

1. Lasts longer than menses

2. Later in life and worsens over time

3. +/- AUB/heavy bleeding

4. Non-midline pelvic pain

5. NO N/V/D/HA

6. Presence of dyspareunia

Primary Dysmenorrhea Evaluation

Clinical diagnosis of exclusion

Dysmenorrhea Evaluation

1. Hx

2. Pelvic exam

3. Diagnostics

Hx Dysmenorrhea Evaluation

1. Confirm sxs and eval secondary dysmenorrhea

2. Prior tx: pain that improved w/ NSAIDs or hormones

Pelvic Exam Dysmenorrhea Evaluation

1. Masses

2. Cervical discharge

3. Focal tenderness

4. Uncover possible causes of secondary

Diagnostics Dysmenorrhea Evaluation

1. Labs: +/- NAAT CT/NG, UA

2. Imaging - Transvaginal US to r/o anatomic abnormality

3. Laparoscopy, if suspecting endometriosis

Conservative Tx of primary dysmenorrhea

Exercise and Heat

First Line Tx for Primary Dysmenorrhea

1. NSAIDs for 2-3 mo

2. Mefenamic acid (rx only), IBU and naproxen > actaminophen