10: Oral Contraceptives, Menopause, HRT

Question 1

What is menopause?

Answer 1

Permanent cessation of menstruation
Loss of ovarian follicular activity

Avg. age 51 (45-55)

Question 2

What is the climacteric period?

Answer 2

Run-up to menopause, period of transition

Question 3

Symptoms of menopause

Answer 3

Hot flushes
Urogential atrophy, dyspareunia
Sleep disturbance
Depression
Loss of libido
Joint pain

Question 4

What changes occur to the HPG axis during menopause?

Answer 4

No ovarian activity -> no oestradiol/inhibin B -> no negative feedback onto hypothalamus

So increased GnRH -> Increased FSH/LH

Question 5

Complications of menopause

Answer 5

Osteoporosis due to oestrogen deficiency - loss of bone matrix, 10-fold increased risk of bone fracture

CVD disease - same risk as men by age of 70 (men normally higher risk)

Question 6

Indications for HRT in menopause?

Answer 6

To control vasomotor symptoms (hot flushes)

Question 7

Why give both oestrogen AND progesterone in HRT?

Answer 7

Oestrogen causes endometrial proliferation -> risk of endometrial carcinoma

So for women with uterus, give with progesterone to prevent endometrial hyperplasia

Women with previous hysterectomy = E only

Question 8

What are the ways in which you can give HRT?

Answer 8

1. Cyclical: E (everyday) + P (12-14 days)

2. Continuous combined

Question 9

What are the different oestrogen preparations?

Answer 9

Oral
Transdermal patch
Intravaginal

Question 10

Pharmacokinetics of oestrogens?

Answer 10

Estradiol is well absorbed BUT high first pass metabolism -> low bioavailability

Estrone sulphate = conjugated oestrogen

Ethinyl estradiol = semi-synthetic oestrogen. Ethinyl group protects from FPM

Transdermal patch -> reduced FPM

Question 11

Side effects of HRT

Answer 11

Breast cancer
CHD
DVT
Stroke

BUT risk of complications is VERY LOW in women in postmenopausal in 50s

Question 12

WHI trials showed increased risk of CHD events in women taking HRT. Mean age was 63yrs.

Why would risk of heart disease from taking HRTs be higher in women in their 60s compared to 50s?

Answer 12

Oestrogen lowers lipids in endothelium of vessels, so protective. BUT it also has pro-thombotic/inflammatory effects.

Baseline risk of atherosclerosis higher in 60yr old women compared to 50s.

So if you gave HRT to younger post-menopausal women, the protective effects of oestrogen would be more prevalent.

If you gave HRT to women in 60s with established atherosclerosis, you would get increased risk of CHD

TIMING OF EXPOSURE is important

Question 13

What are the effects of oestrogen and progesterone on postmenopausal women 50-59yrs old?

Answer 13

Oestrogen: IMPROVES lipid profile and endothelial function

Addition of synthetic progestins (progesterone) NEGATES this effects

Question 14

What are the effects of oestrogen and progesterone on postmenopausal women >60yrs old?

Answer 14

If you already have atherosclerosis, you are more susceptible to prothrombotic/proinflammatory effects of oestrogen

Question 15

Give 2 other drugs used for menopause

Answer 15

Tibolone = Synthetic prohormone
Oestrogenic, progestogenic and weak androgenic actions. Reduces fracture risk BUT increased risk of stroke

Raloxifene = Selective Estrogen Receptor Modulator (SERM).
Oestrogenic in BONE - reduced risk of vertebral fractures
ANTI-oestrogenic in breast/uterus - reduces breast cancer risk
Does NOT reduce vasomotor symptoms.
INCREASED risk of stroke + VTE

Tamoxifen = Anti-oestrogenic on breast
Used to treat oestrogen-dependent breast tumours & metastatic breast cancers

Question 16

What is premature ovarian insufficiency? Causes?

Answer 16

Menopause occurs before age of 40
1% of women

Causes: Autoimmune, surgery, chemo, radiation

Question 17

What is combined oral contraceptive?

Answer 17

Oestrogen (Ethinyl estradiol) + progestogen
Suppresses ovulation
E+P -> negative feedback onto hypo/pituitary
P -> thickens cervical mucus

Take for 21 days (or 12 weeks), stop for 7 days

Question 18

When do you indicate progesteron-only contraceptives?

Answer 18

When oestrogen is contra-indicated:
Smokers, >35yrs, migraine with aura

Must be taken at same time each day
Short half-life/DOA

Long-acting preparations may be given via intra-uterine system

Question 19

What are the different emergency (post-coital) contraceptives?

Answer 19

1. Copper IUD (up to 7 days)
   - Intrauterine
   - Exclude pregnancy first
   - Affects sperm viability + function
   - Preferred for obese/overweight patients
2. Ulipristal (up to 120 hours)
   - Anti-progestin
   - Delays ovulation + impairs implantation
3. Levonorgestrel (within 72 hours)