Menopause, HRT & Oral Contraceptives

Question 1

What is menopause? When does it occur?

Answer 1

Permanent cessation of menstruation (amenorrhoea >12 months) and loss of ovarian follicular activity

Average age 51 (range 45-55)

Question 2

What is the term given to the transition period into menopause?

Answer 2

Climacteric period

Normal => oligomenorrhoea => amenorrhoea

Question 3

State some symptoms of menopause

Answer 3

• Hot flushes (head, neck, upper chest)
• Urogenital Atrophy which leads to dyspareunia (difficult or painful sexual intercourse)
• Sleep disturbance
• Decreased libido
• Depression
• Joint pain
• Symptoms usually diminish/disappear with time.

Question 4

What do the ovaries produce that has a negative feedback effect? How does this feedback change in menopause? What effect does this have?

Answer 4

Oestradiol and inhibin B

Loss of ovarian follicular activity => decreased production of oestradiol and inhibin => less negative feedback => High LH and FSH

Question 5

State and explain the main complications of menopause

Answer 5

Osteoporosis: loss of the protective effect of oestrogen on bone = loss of bone matrix

Cardiovascular disease: women are protected against cardiovascular disease before menopause

Question 6

What is the risk of giving oestrogen as part of HRT, and how is this risk prevented?

Answer 6

Causes endometrial hyperplasia, which increases the risk of endometrial carcinoma.

You give progestogens as well to block this effect on the endometrium.

Question 7

In which subset of patients would you give oestrogen only as part of HRT?

Answer 7

Patients who have had a hysterectomy (no uterus so there is no endometrium)

Question 8

Describe the 2 different formulations of HRT.

Answer 8

Cyclical = take oestradiol every day, and then for the last 12-14 days you take progesterone

Combined continuous = take a little oestrogen and progesterone every day

Question 9

State 4 different types of oestrogen preparations

Answer 9

1. Oral estradiol (1mg)
2. Oral conjugated equine oestrogen e.g. Estrone sulphate (0.625 mg)
3. Transdermal (patch) oestradiol (50 microgram/day)
4. Intravaginal

Question 10

Describe the absorption and metabolism of oestradiol, stating why oral doses are higher

Answer 10

Oestradiol is absorbed well but is heavily metabolised in the liver so the bioavailability is very low.
This means that in oral preparations, you must give a high dose of oestradiol.

Question 11

Name a semi-synthetic oestrogen that’s used in oral contraceptives

Answer 11

Ethinyl oestradiol 
(The ethinyl group protects the drug from hepatic first pass metabolism)

Question 12

What is the difference between the types and dose of oestrogen given in HRT compared to the oral contraceptive?

Answer 12

In HRT you are just giving a little bit of oestrogen to prevent the symptoms of menopause.

In contraception, you are trying to suppress the HPG axis so you give a more potent type of oestrogen.

Question 13

*State some side-effect/risks of HRT

Answer 13

Breast cancer
Coronary heart disease
Deep Vein thrombosis
Stroke
Gallstones

*Note: absolute risk of complications for healthy symptomatic postmenopausal women in their 50s taking HRT for five years is very low

Question 14

What influences the risk of coronary heart disease following postmenopausal HRT?

Answer 14

Timing of exposure
- No excess risk in younger menopausal women (50-59)
- In older women (>60), susceptible to prothrombotic &
proinflammatory effects of oestrogen

Question 15

Name a synthetic prohormone that has oestrogenic, progestogenic and weak androgenic effects.

Answer 15

Tibolone

Question 16

State the effects of using tibolone

Answer 16

It reduces the risk of fracture

It increases the risk of stroke

Question 17

What is raloxifene and what does it do?

Answer 17

It is a selective oestrogen receptor modulator (SERM)

• In bone it has oestrogenic effects and reduces the risk of fracture
• In breast and uterus it has anti-oestrogenic effects and reduces the risk of breast cancer

Question 18

What are the problems with raloxifene?

Answer 18

• It does not reduce vasomotor symptoms (hot flushes)

- It is associated with an increased risk of fatal stroke and venous thromboembolism

Question 19

What is tamoxifen, and what is it used for?

Answer 19

It is an anti-oestrogenic on breast tissue.

Used to treat oestrogen-dependent breast tumours & metastatic breast cancers

Question 20

What is Premature Ovarian Insufficiency? List some causes

Answer 20

Menopause before the age of 40

Autoimmune
Surgery
Chemotherapy
Radiation

Question 21

What type of oestrogen and progestogen is used in the combined oral contraceptive pill?

Answer 21

Oestrogen - ethinyl oestradiol

Progestogen - levonorgestrel or norethisterone

Question 22

State the purpose of oral contraceptives, and how is this achieved? When do you take the pill?

Answer 22

Suppress ovulation

• Oestrogen + progestogen has negative feedback actions at hypothalamus/pituitary
• Progestogen thickens cervical mucus preventing sperm entry into the uterus

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

Question 23

When would you use the progesterone-only pill?

Answer 23

If oestrogen is contraindicated – this is if there is an increased risk of thrombosis (oestrogen has pro-coagulant effects)

Question 24

What is an important point to remember about when to take the progesterone-only pill?

Answer 24

Must be taken at the same time each day

• Short half-life
• Short duration of action

Question 25

How may long acting preparations of the progesterone-only pill may be given?

Answer 25

Via an intra-uterine system (device called Mirena)

• Provides long term contraception

Question 26

What 3 things can you use for emergency (post-coital) contraception?

Answer 26

Copper intrauterine contraceptive device that affects sperm viability and function, and inhibits fertilisation (Effectiveness not reduced in overweight/obese women)

Levonorgestral (within 72 hours after intercourse)

Ulipristal (within 120 hours after intercourse):

• Has anti-progestin activity
• Delays ovulation by as much as 5 days
• Impairs implantation

Question 27

In younger women (50-59), synthetic progestins have what effect on the oestrogen they are combined with?

Answer 27

Oestrogen has beneficial effects on lipid profile &

endothelial function but synthetic progestins negate these effects.