Rachel K. Casey, MD FACOG Pediatric and Adolescent Gynecology Pediatric Specialists of Virginia Mohsen Ziai Pediatric Conference Inova Children’s Hospital November 4th, 2016

I have no financial disclosures

LEARNING OBJECTIVES

Describe normal menstrual cycles in adolescents

Recognize abnormal patterns in menstruation

Understand appropriate work up for abnormal menstrual patterns

Manage heavy and intermenstrual menstrual bleeding in adolescents

MENSTRUAL PATTERNS IN ADOLESCENCE

Normal Menstrual Cycles in Young Females

Menarche (median age) 12.43

Mean cycle interval 32.2 days

Menstrual cycle interval range 21-45 days

Menstrual flow length 7 days or less

Menstrual product use 3-6 pads/tampons per day

Joint Committee Opinion ACOG and AAP November 2006, Reaffirmed 2009

ADOLESCENCE & CYCLE LENGTH

The early years Anovulatory cycles are normal 21-45 days is most common

Earlier menarche = earlier ovulatory cycles

Fully ovulatory cycles may take 8-12 years

90% of girls have 27-35 day cycles by

7th gynecological year1

1WHO Task Force on Adolescent Reproductive Health. J Adolesc Health Care 1986

COMMON CAUSES OF IRREGULAR MENSES Pregnancy!

Anovulation secondary to immature HPO axis

Endocrine Thyroid dysfunction

PCOS Poorly controlled GM Cushing disease Premature ovarian insufficiency Congenital Adrenal Hyperplasia

Acquired conditions Hypothalamic dysfunction related to stress Medications Female Athlete Triad Easing disorder

Tumors Ovarian Adrenal Prolactinoma

Abnormal uterine bleeding (AUB) - Heavy menstrual bleeding (AUB/HMB)

- Intermenstrual bleeding (AUB/IMB)

PALM: Structural Causes Polyp (AUB-P)

Adenomyosis (AUB-A) Leiomyoma (AUB-L)

Malignancy/Hyperplasia (AUB-M)

COEIN: Nonstructural Causes Coagulopathy (AUB-C)

Ovulatory Dysfunction (AUB-O) Endometrial (AUB-E)

Iatrogenic (AUB-I) Not yet classified (AUB-N)

CLASSIFICATION OF ABNORMAL BLEEDING

MENSTRUATION IN GIRLS AND ADOLESCENTS: USING THE MENSTRUAL CYCLE AS A

VITAL SIGN

Menstruation in Girls and Adolescents: Using the Menstrual Cycle as a Vital Sign. AAP Committee on Adolescence. ACOG Committee on Adolescent Health Care. Pediatrics. 2006.

Menarche: Pubertal history

Last menstrual period Prior menses:

Cycle length/range: Duration of flow: Light/medium/heavy: Flooding:

Missing school/activities: Treatment for menses: Anemia:

Bleeding history epistaxis, bruising, gums,

surgical

Medical history Social history Confidential interview Sexual activity, eating

disorders, exercise

Family history PCOS Maternal menstrual history Bleeding disorder history

Exam Full PE exam Tanner staging Skin findings Internal pelvic exam rarely

indication

Menses has not started 3 years after thelarche

Menses has not started by 13 with No signs of puberty

Menses has not started by 14 with Signs of hirsutism

Concern for eating disorder/over exercising

Concern for outflow obstruction

Menses has not started by age 15

Are regular, occurring monthly, and then become markedly irregular

Occur more frequently than every 21 days or less frequently than every 45 days

Occur 90 days apart even for one cycle

Last >7 days

Require frequent pad/tampon changes (soaking more than 1 every 1–2 hours)

Pelvic Ultrasound

Transabdominal only Translabial If additional images needed

Rule out structure cause Fibroid, polyp, tumor

Not routinely indicated

Common Labs

Pregnancy test TSH Prolactin CBC Ferritin (if anemic) STI screen (if sexually

active)

12 yo with abnormal uterine bleeding Prolonged bleeding 21 days

Menarche: 6 months ago

LMP: 3 weeks ago Prior menses: 45 days

Cycle length/range: 28-45 days

Duration of flow: 5-21 days Light/medium/heavy: variable Flooding: yes

Missing school/activities: yes

Treatment for menses: no

Anemia: no

Confidential Interview: negative

Exam: normal pubertal development

DIFFERENTIAL DIAGNOSIS Pregnancy!

Anovulation secondary to immature HPO axis

Endocrine Thyroid dysfunction

PCOS Poorly controlled GM Cushing disease Premature ovarian insufficiency Congenital Adrenal Hyperplasia

Acquired conditions Hypothalamic dysfunction related to stress Medications Female Athlete Triad Easing disorder

Tumors Ovarian Adrenal Prolactinoma

ANOVULATORY CYCLES: AUB-O

In absence of ovulation, corpus luteum does not develop

Progesterone is not secreted by the ovary

Continued proliferation of endometrium by unopposed estrogen

Fragile, vascular proliferative endometrium sheds irregularly

Menses has not started 3 years after thelarche

Menses has not started by 13 with No signs of puberty

Menses has not started by 14 with Signs of hirsutism

Concern for eating disorder/over exercising

Concern for outflow obstruction

Menses has not started by age 15

Are regular, occurring monthly, and then become markedly irregular

Occur more frequently than every 21 days or less frequently than every 45 days

Occur 90 days apart even for one cycle

Last >7 days

Require frequent pad/tampon changes (soaking more than 1 every 1–2 hours)

Work up CBC, ferritin

Management Expectant management Acute bleeding episode Provera (Medroxyprogesterone) 10mg po x 10 days Inhibits GnRH Transforms proliferative into secretory endometrium Bleeding usually occur 2-7 days after the progestin is finished

Long term menstrual regulation “Hormone Pills” - combination oral contraceptive pills Anemia/iron deficiency: recommend OCPs No anemia: expectant management, counsel regarding options

17 yo with irregular menstrual bleeding for 2 years Menarche: 10 yrs LMP: 4 months ago Prior menses: 2 month prior to that

Cycle length/range: 60-120 days Duration of flow: 2-18 days Light/medium/heavy: variable Flooding: yes

Missing school/activities: no Treatment for menses: no Anemia: no Confidential Interview: sexually active

Pertinent Exam Findings Obese Acanthosis nigricans Coarse hair Face Lower abdomen Back

DIFFERENTIAL DIAGNOSIS Pregnancy!

Anovulation secondary to immature HPO axis

Endocrine Thyroid dysfunction

PCOS Poorly controlled GM Cushing disease Premature ovarian insufficiency Congenital Adrenal Hyperplasia

Acquired conditions Hypothalamic dysfunction related to stress Medications Female Athlete Triad Easing disorder

Tumors Ovarian Adrenal Prolactinoma

Menses has not started 3 years after thelarche

Menses has not started by 13 with No signs of puberty

Menses has not started by 14 with Signs of hirsutism

Concern for eating disorder/over exercising

Concern for outflow obstruction

Menses has not started by age 15

Are regular, occurring monthly, and then become markedly irregular

Occur more frequently than every 21 days or less frequently than every 45 days

Occur 90 days apart even for one cycle

Last >7 days

Require frequent pad/tampon changes (soaking more than 1 every 1–2 hours)

Laboratory evaluation for androgen abnormalities HCG TSH Prolactin Testosterone Estradiol FSH/LH SHBG 17-Hydroxyprogesterone DHEA-S

Strong suspicion for PCOS HbA1C Lipid panel

Challenging diagnosis in adolescents

Androgen Excess Society diagnostic criteria Clinical or serum hyperandrogenism Ovulatory dysfunction

Importance of diagnosis & treatment Protection of endometrium Management of irregular menses Reduction in hirsutism and acne Decrease risk of diabetes Reduce cardiovascular risks

Combination estrogen/progestin OCPs 30mcg ethynyl estradiol Regulate menses Protects endometrium

Decreases adrenal androgen secretion Increases SHBG

Progestin only therapy Provera withdrawal bleed q 2-3 months Progesterone only pill Contraindication to estrogen

Levonorgesterol Intrauterine Device Endometrial protection

13 yo with heavy menstrual bleeding Menarche: 12 LMP: 4 weeks ago Cycle length/range: 28-32 days Duration of flow: 6-7 days Light/medium/heavy: very heavy, using 8-10 pads/day Flooding: yes, multiple episodes

Missing school/activities: no Treatment for menses: no Anemia: suspected, complains of fatigue and low energy

Menses has not started 3 years after thelarche

Menses has not started by 13 with No signs of puberty

Menses has not started by 14 with Signs of hirsutism

Concern for eating disorder/over exercising

Concern for outflow obstruction

Menses has not started by age 15

Are regular, occurring monthly, and then become markedly irregular

Occur more frequently than every 21 days or less frequently than every 45 days

Occur 90 days apart even for one cycle

Last >7 days

Require frequent pad/tampon changes (soaking more than 1 every 1–2 hours)

Pertinent history Maternal history of postpartum hemorrhage requiring transfusion

Labs Hemoglobin 8.3 Hematocrit 24% Ferritin 3 ng/dL

HEAVY MENSTRUAL BLEEDING DEFINED

Term “menorrhagia” has been retired

Bleeding that lasts longer than 7 days or results in the loss of >80mL of blood per cycle

Methods to predict blood loss >80mL: Low ferritin level (<20 ng/mL) Clots >1 inch in size Changing pad or tampon more more frequently than every hour Flooding Pictoral Bleeding Assessment Calendar Scores >100 are 80% sensitive and specific for the dx1

Higham et al. Br J Obstet Gynecol 1990

Initial Labs

Pregnancy test

TSH

Prolactin

CBC

Ferritin (if anemic)

STI screen (if sexually active)

Hemostasis Labs

PT/PTT

VWD Panel VWF Ag, VWF activity

(VWF:Rco) , FVIII During pill free week 3 sets 2+ weeks apart

Platelet aggregation studies

Fibrinogen

Thrombin time

Oral contraceptive pills to control HMB

Iron supplementation

Referral to hematology *Multidisciplinary Heme/Gyn Clinic*

TREATMENT OF ACUTE HEAVY MENSTRUAL BLEEDING

IV estrogen (Premarin)

OCP pill taper QID first day TID x 3 days BID x 14 days QD for at least one month Monophasic 30mcg ethinyl estradiol pill preferred

Progesterone – high dose Medroxyprogesterone PO or IM

GnRH analog: depo-leuprolide acetate (Lupron) Special situations Short term use, causes osteopenia

MAINTENANCE THERAPY Estrogen/Progesterone Combined oral contraceptive pills Consider extended cycle

Vaginal ring (NuvaRing) Transdermal patch (OrthoEvra)

Progesterone only Depo Provera

(medroxyprogesterone acetate) MicroNor/norethindrone Aygestin/norethindrone acetate Levonorgestrel intrauterine device Etonorgestrel subdermal implant

NONHORMONAL TREATMENTS NSAIDs

DDAVP Synthetic analog of vasopressin (ADH) Used for patients with Type 1 vWD

Antifibrinolytics Tranexamic acid (Lysteda) Use for 5 days maximum, during menses Has been shown to decrease PBAC scores and control heavy menstrual

bleeding in adolescents with bleeding disorders

Consider in conjunction with OCP

TREATMENT OF ANEMIA

Treat iron deficiency anemia aggressively!

4-6 mg/kg elemental Fe per day for 1 month 325mg Ferrous Sulfate = 65mg elemental Fe

Re-check CBC in a month, most are replete

Control heavy menstrual bleeding

Maintenance: Multivitamin w/ Fe Note: Gummy vitamins contain no Fe.

Contraindications

Combination OCPs

Clotting disorders History of DVT/PE

Migraine with aura or focal neurological

deficit Hypertension/vascular

disease

Progesterone Only OCPs

Thickens cervical mucus

Suppresses ovulation via negative feedback Decreased GnRH pulsatility Decreased pituitary

responsiveness Suppression of LH and FSH Inhibits mid-cycle LH surge

Decreased tubal motility

Endometrial atrophy and localized edema

General Menstrual Health

Efficacy* Dysmenorrhea Ovarian cancer

Safety Blood loss Endometrial cancer

Reversibility PMS Acne & hirsutism

Side effects Anovulatory bleeding

Endometriosis pain

Ovarian cysts Benign breast disease

Daily administration

Expense

Access

Storage & ready access

? Bone health ?

Estrogen Progesterone

Nausea Headaches Sore/enlarged breasts

Edema Abdominal bloating Menstrual irregularities

HTN

Normalize 3-6 months after

discontinuation

Cholestatic Jaundice

Rare

Reversible

Hyperkalemia

Drosperinone-containing

Hepatic neoplasm

Reversible

VTE

0.5:10,000 women < 20

year old

Increased relative risk

Low absolute risk

Incidence Relative Risk

Young Women 4-5 1

Pregnant Women 48-60 12

COC with 50mcg+ 24-60 6-10

COC less than 50mcg 12-20 3-4

Pregnancy

No increase birth defects

No additional prenatal tests

Myocardial Infarction

Young, healthy,

nonsmoker

No increased risk

Stroke

Young, healthy,

nonsmoker

No increased risk*

World Health Organization. Medical Eligibility Criteria for Contraceptive Use. 2016.

Risk Category

1 = no restriction for the use of the contraceptive method 2 = advantages of method generally outweigh the theoretical or proven risks 3 = theoretical or proven risks generally outweigh the advantages 4 = unacceptable health risk if the contraceptive is used

Contraceptive When to start Additional Contraception

Tests prior to initiation

Combination hormonal contraceptives

Anytime *Quick start *First-start *Sunday start

Use back-up method or abstain for 7 days (If >5 days after menses started)

Blood pressure

Progestin-only pill

Anytime use back-up method or abstain for 2 days (If >5 days after menses started)

None

If she has no symptoms or signs of pregnancy and meets any one of the following criteria:

is ≤7 days after the start of normal menses

has not had sexual intercourse since the start of last normal menses

has been correctly and consistently using a reliable method of contraception

is ≤7 days after spontaneous or induced abortion

is within 4 weeks postpartum

is fully or nearly fully breastfeeding (exclusively breastfeeding or the vast majority [≥85%] of feeds are breastfeeds),* amenorrheic, and <6 months postpartum

U.S. Selected Practice Recommendations for Contraceptive Use, 2013

Monthly cycling 21/7

Shortened pill-free interval

Extended cycle use

Estrogen

Progesterone

Ethinyl estradiol

20-50 micrograms

>35 micrograms rare

4th Generation: Drosperinone

Anti-androgenic properties

3rd generation: Desonorgestrel

Least androgenic

2nd generation: Levonorgestrel

More androgenic

1st generation: Norethindrone Irregular spotting

Monophasic

Multiphasic Biphasic Triphasic

Combination OCP general use (contraception, painful menses)

“Junel” “Loestrin” Norethindrone/ethinyl estradiol 1mg/20mcg

Heavy menstrual bleeding or PCOS “Lo-Ovral-28” or “Cryselle” Norgestrel/ethinyl estradiol 0.3mg/30mcg

LONG ACTING REVERSIBLE CONTRACEPTION IS RECOMMENDED

Gynecology Clinic Menstrual abnormalities Ovarian cysts/masses Vulvovaginal complaints Abnormalities of the female reproductive tract

Multidisciplinary Clinics Polycystic Ovarian Syndrome Dr. Rinku Mehra, Endocrinology Kristen Hami, Registered Dietician

Heavy Menstrual Bleeding (2017) Dr. Carly Varela, Hematology/Oncology

Ambulatory Surgery Center Outpatient procedures Located in PSV building

THANK YOU!

Rachel Casey, MD 703-876-2788

Rachel.Casey@inova.org Rcasey@psvcare.org