Menopause and HRT

Question 1

Menopause average onset

Answer 1

51

Question 2

Who goes through menopause early?

Answer 2

Smokers
Hysterectomized
49

Question 3

Perimenopause symptoms

Answer 3

Cycle irregularity
Vasomotor symptoms (hot flashes, night sweats)
-psychological symptoms (mood, anxiety)
-Sleep disturbances
-Sexual issues (vaginal dryness, dyspareunia
-10-15 fold increase in FSH
-4-5 fold increase LH
-90% decrease in estrogen

Question 4

Women’s health initiative (WHI)

Hormone replacement finding

Answer 4

Combined hormone intervention halted!
Increased BC, CHD, stroke, and PE
-Estrogen only halted 2 yrs later

Question 5

WHI dietary modification

Answer 5

Small decrease in fat accumulation

Small decrease in CHD, stroke and CVD

Question 6

WHI

Calcium / vitD supplementation

Answer 6

-1g/d Ca, 400 IU vitD
-No change in fractures
-small increase in BMD
Increased risk of kidney stones

Question 7

WHI Adverse events interpretation

Answer 7

Increased risk of 4 in 1000 (0.4%)

• relative risk is noticeable, but absolute risk is so low.
• Eg, a 400% increase sounds scary but when talking about 1 in 1000 to begin with it doesn’t mean much.

Question 8

WHI and window of opportunity for HRT

Answer 8

The window of opportunity for the maximal beneficial effect of HT on total mortality and CHD appears to be:
when HT is initiated within 6 years of menopause and/or before age 60, and continued for 5 years or more

Question 9

HRT for hysterectomized patients

Why?

Answer 9

Estrogen only.

Progesterone is used to protect against uterine/endometrial cancer

Question 10

1. Continuous cyclic E-P regimen

Answer 10

• E daily
• P last 12-14 d of 28 d ccle
• Withdawal bleeding in 90% pt after termination of prog
• Oral: 0.625 mg CEE + 5/10 mg MPA
• Transderm: 50 ug E2 + 0.14/0.25 mg norethindrone acetate

Question 11

2. Continuous Combined E-P regimen

Answer 11

• E+P continuously
• Oral: 0.625 mg CEE + 5/10 mg MPA
• Transderm: 50 ug E2 + 0.14/0.25 mg norethindrone acetate

-Results in endometrial atrophy and absence of bleeding
-Initially causes spotting/bleeding
(resolves in 6-12 mo, can increase E or decrease P, less likely 2 yr out from menopause)

Question 12

3. Continuous long cycle E-P regimen

Answer 12

• E daily
• P every other month for 12-14 d
• Bleeding may be heavier and last longer than continuous cyclic regimen

Question 13

4. Intermittent combined (continuous pulsed or pulsed P) regimen

Answer 13

• 3 days E followed by 3 days E+P; repeated without interuption
• Decreases incidence of bleeding
• Allows lower P dose, decreased ADR

Question 14

Quarterly Progestin Regimen

Answer 14

MPA for 14 d every 3 mo

higher incidence of endometrial hyperplasia

Question 15

Low dose therapy

Answer 15

0. 45 mg CEE + 1.5 mg MPA
   - symptom relief and BMD can be maintained
   - May have lower long term risk

Question 16

ADRs of progestogens

Answer 16

Irritability, depression, HA, sleep disturbance, bloating: “premenstrual symptoms”

Question 17

Micronized Progesterone

Answer 17

100-200 mg/d

less bleeding, less effect on blood lipids

Question 18

Levonorgestrel IUD (Mirena,Skyla)

Answer 18

HRT is offlabel use

-high intra-uterine but low systemic P levels, atrophic endometrium

Question 19

Drospirenone (Yasmin, Yaz)

Answer 19

• Progestogenic, anti-androgenic, anti-mineralocorticoid effects
• Decreased hyperplasia, no hyperkalemia

Question 20

How do women get increased Testosterone levels?

Answer 20

Fall in SHBG after menopause increases free T

Question 21

What is the major source of post menopause testosterone?

Answer 21

Ovary