Oral Contraceptives, Menopause and HRT

Question 1

What is menopause?

Answer 1

Permanent cessation of menstruation - amenorrhoea for more than 12 months - from the loss of ovarian follicular activity

NOTE: usually happens between 45-55 yrs

Question 2

What is the term given to the period of transition just beforemenopause? Describe this period of transition.

Answer 2

Climacteric period

You go from having normal regular cycles and then it becomes a little irregular (oligomenorrhoea) and then it progresses to amenorrhoea.

Question 3

State some symptoms of menopause.

Answer 3

Hot flushes  
Urogenital Atrophy (leads to dyspareunia – difficult or painful sexual intercourse) 
Sleep disturbance  
Decreased libido  
Depression  
Joint pain

Question 4

What do the ovaries produce that feeds back on the HPG axis?

Answer 4

Oestradiol and Inhibin B

Question 5

How does this feedback change in menopause?

Answer 5

There is a loss of ovarian follicular activity so you get a decreased production of oestradiol and inhibin

This means that there is less negative feedback on the HPG axis

Question 6

What would you expect the LH and FSH levels of a menopausal woman to be?

Answer 6

High – because of the loss of oestrogen and inhibin production

Question 7

What are the main complications of menopause?

Answer 7

Osteoporosis (the protective effect of oestrogen on bone is lost)

Cardiovascular disease (women are protected against cardiovascular disease before menopause)

Question 8

What are the risks of giving oestrogen as part of HRT?

Answer 8

Endometrial hyperplasia, which increases the risk of endometrial carcinoma (also increases risk of breast cancer)

Question 9

How is this effect of oestrogen prevented?

Endometrial hyperplasia, which increases the risk of endometrial carcinoma

Answer 9

You give progesterone as well as oestrogen

The progesterone blocks this effect of oestrogen on the endometrium and, hence, prevents endometrial hyperplasia

Question 10

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

Answer 10

Patients who have had a hysterectomy

There is no uterus so there is no endometrium to stimulate with oestrogen

Question 11

Describe the 2 different formulations of HRT.

Answer 11

Cyclical – take oestradiol every day and then 12-14 days in you take progesterone

Combined continuous – take a little oestrogen and progesterone every day

Question 12

State 4 different types of oestrogen preparations.

Answer 12

Oral oestradiol (1 mg) - larger dose as 1st pass metabolism

Oral conjugated equine oestradiol (0.625 mg)

Transdermal oestradiol (50 mcg/day)

Intravaginal

Question 13

Describe the absorption and metabolism of oestradiol.

Answer 13

Oestradiol is absorbed well but it is heavily metabolised in the liver (first pass) so the bioavailability is very low.

This means that in oral preparations, you must give a high dose of oestradiol.

Question 14

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

Answer 14

Ethinyl oestradiol

The ethinyl group protects the drug from hepatic first pass metabolism.

Question 15

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

Answer 15

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 16

State some side-effect/risks of HRT.

Answer 16

Breast cancer

Venous thromboembolism

Stroke

Gallstones

Question 17

How does HRT affect cardiovascular disease risk?

Answer 17

There is an increased risk of coronary heart disease

The timing of exposure is important in terms of cardiovascular disease risk – older patients who are started on HRT have an increased risk of CHD but in younger women there was no increased risk

Question 18

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

Answer 18

Tibolone

Question 19

What is this drug used for and what are the risks?

Tibolone

Answer 19

It reduces the risk of fracture

It increases the risk of stroke

Question 20

What is raloxifene and how does it work?

Answer 20

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 21

What are the problems with raloxifene?

Answer 21

It is associated with an increased risk of fatal stroke and VTE

Question 22

What is tamoxifen?

Answer 22

Anti-oestrogenic on breast tissue

Question 23

What is tamoxifen used for?

Answer 23

Treatment of oestrogen-dependent breast tumours and metastatic breast cancers

Question 24

What is the term given for menopause before the age of 40?

Answer 24

Premature Ovarian Insufficiency

Question 25

What could POI be caused by?

Answer 25

Autoimmune
Surgery
Chemotherapy
Radiotherapy

Question 26

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

Answer 26

Ethinyl oestradiol

Question 27

What types of progestogen is used in the combined oral contraceptive pill?

Answer 27

Levonorgestral

Norethistrone

Question 28

What other effect do progestogens have that reduces the chance of conception?

Answer 28

It thickens cervical mucus meaning that it is more difficult for sperm to penetrate it

Question 29

When would you use the progesterone only pill?

Answer 29

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

Question 30

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

Answer 30

It must be taken at the same time every day

Question 31

What is the name given to the long-acting intra-uterine progesterone device?

Answer 31

Mirena

Question 32

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

Answer 32

Copper IUD (affects sperm viability and function and inhibits fertilisation)

Levonorgestral (within 72 hours – high dose progesterone)

Ulipristal (within 120 hours)
 Anti-progestin activity
 Delays ovulation by as much as 5 days
 Impairs implantation