ic16 EE and Norethindrone + ic18 menstrual cycle disorders + menopause

Question 1

Definition of Amenorrhea

Classification?

Answer 1

no bleeding for 3 months

Primary: no menses by age 15

Secondary: no bleeding for 3 cycles (3 months)

Question 2

Who does Secondary Amenorrhea usually occur in?

Answer 2

< 25yo with history of menstrual irregularities

Competitive sports
Massive weight loss

Question 3

3 causes of Amenhorrea

Answer 3

1) Anatomical
Pregnancy
Uterine structure abnormalities

2) Endocrine disturbances

3) Ovarian insufficiency / failure

Question 4

Definition of Menorrhagia

Answer 4

Heavy bleeding

> 80ml per cycle OR bleeding > 7 days per cycle

Question 5

Pharmacological Treatment for Menorrhagia

Answer 5

Contraception desired:
1) COC / Progestin only (IUD, Oral, Injection)
- Estrogen-only NOT USED
- (recap) Progestin causes endometrial atrophy

No contraception desired:
1) NSAIDs

2) Tranexamic acid
Slow breakdown of blood clots

3) Cyclic progesterone

Question 6

Non-pharmacological treatment for Menorrhagia (2 points)

Answer 6

1) Endometrial ablation
Remove endometrial lining

2) Hysterectomy
Remove entire uterus

Question 7

What is Dysmenorrhea

Answer 7

Crampy pelvic pain with or just before menses

Question 8

MOA for Primary Dysmenorrhea and Secondary Dysmenorrhea

Answer 8

Primary:
Release Prostaglandins and Leukotrienes → vasoconstriction → Cramp

Secondary:
Endometriosis

Question 9

Pharmacological treatment for Dysmenorrhea (1st, 2nd, 3rd line)

Answer 9

NSAIDs (1st line)
Inhibit production of Prostaglandins
Pain relief

COC (2nd line)

Progestin IUD (Levonorgestrel), injections (3rd line)
Progestin causes thinning of endometrial / atrophy → Less prostaglandins produced → Lesser vasoconstriction → Less pain

Question 10

Cause of Polycystic Ovary Syndrome (PCOS)?

Answer 10

Ovaries producing more androgens (male hormones) → Cysts form in ovaries

Question 11

Symptoms of PCOS

Answer 11

Menstrual irregularities
Amenorrhea
Menorrhagia

Androgenic symptoms
Acne
Hirsutism
Metabolic disorder / Insulin resistance

Question 12

Treatment for PCOS (2 Points)

Answer 12

COC
Drospirenone (4th gen. cos antiandrogenic)

Metformin
Counter insulin resistance by increasing glucose uptake of muscle cells (secondary MOA)

Question 13

What happens during Perimenopause?

How to detect Perimenopause?

Answer 13

Estrogen production starts to decrease → causing menses to become unpredictable

Can test FSH level
FSH high if Estrogen is reduced

Question 14

Symptoms of Menopause (4 points)

Answer 14

1) Vasomotor symptoms (most common)
Hot flushes
Night sweats
Fast, irregular HR
Cold sweats, perspiration

2) Genitourinary syndrome (GSM)
Genital dryness
Burning, irritation, pain
Lubrication difficulty
Impaired libido, painful intercourse
Dysuria
Urinary urgency
Recurrent UTI

3) Psychological
Depression, anxiety
Mood swings

4) Bone fragility
Lower estrogen → More bone loss
↑ risk of osteoporosis, fractures, joint pain

Question 15

Non-pharm treatment for Menopausal symptoms

When should non-pharm be used?

Answer 15

1) Mild Vasomotor
Lower room temp
Less spicy food, caffeine, hot drinks
More exercise
Isoflavones, Black cohosh

2) Mild Vulvovaginal
Non hormonal vaginal lubricants, moisturisers

Should be used only if VMS or GSM symptoms are mild

Question 16

Pharm treatment for Menopausal symptoms (3 points)

Answer 16

Menopausal Hormone Therapy (MHT)

Antidepressants

Gabapentin

Question 17

2 types of MHT, and when should they be used?

Answer 17

Estrogen only
use only for patient without uterus

Estrogen + Progesterone
use if patient has intact uterus

Question 18

When should Estrogen-only be given?

When should Progestin-only be given?

Answer 18

Estrogen-only given for:
- Menopause (MHT) patients without intact uterus to supplement the low Estrogen and reduce symptoms
- Amenhorrhea

Progestin-only given for
- Menorrhagia (heavy bleeding)
- cannot tolerate N/V of estrogen
- breastfeeding
- VTE, migraine w aura

Question 19

Purpose of Progestin in MHT?

Answer 19

To prevent overgrowth of endometrium and reduce risk of endometrial cancer

Question 20

Goal of MHT vs Goal of COC?

Answer 20

MHT: Supplement endogenous estrogen to alleviate symptoms
→ hence use lower dose of estrogen

COC: Suppress HPO axis to avoid ovulation
→ hence use higher dose of estrogen

Question 21

Types of Estrogen only MHT (3 points)

Which are used for Vasomotor symptoms, which are used for Genitourinary symptoms?

Answer 21

1) Systemic oral tablets
for both

2) Systemic gel / patch
for both

3) Local vaginal pessary, creams
only for Genitourinary symptoms, NOT for Vasomotor symptoms (cos no systemic absorption)

Question 22

What is the difference between Continuous-cyclic and Continuous-combined? (bold and underline)

Answer 22

Continuous cyclic:
Progestin taken for 10-14 days
Progestin added on 1st or 15th day
Withdrawal bleeding occurs when progestin is stopped

Suitable for:
Perimenopausal women, where menstrual cycle becomes irregular

Continuous-combined:
Estrogen + Progestin taken everyday
No withdrawal bleeding
Breakthrough bleeding may occur initially

Suitable for:
Post menopausal women, since they are not experiencing anymore periods

Question 23

Role of Progestins in Menopausal Hormone Therapy

Answer 23

Reduce risk of endometrial cancer (AKA counters Estrogen by causing endometrial atrophy, wont overgrow)

Progestins used are mostly 1st and 2nd generation

Question 24

Counselling points for patients on MHT

What kind of monitoring is needed (2 points)

Answer 24

Takes 2-3 months to see improvement in symptoms
Let patient understand risks and benefits of MHT, and the need for monitoring for breast cancer and bleeding

Annual mammography
Monitor for breast cancer

Endometrial surveillance
Any bleeding or bleeding heavier than normal

Question 25

Similarities between Norethisterone / Norethindrone and Ethinyl Estradiol (Distribution and Metabolism)

Answer 25

Highly bound to albumin

Undergo phase 2 glucuronidation and sulfation

Question 26

Why does EE have high half life (13-27hrs)?

Answer 26

After sulfation, EE sulfate can undergo enterohepatic circulation

Question 27

Why can VTE still occur in Norethindrone?

Answer 27

Norethindrone can be converted to EE via metabolism in the liver, resulting in estrogen adverse effects eg. VTE