Oral Contraceptives, Menopause and HRT

Question 1

What is menopause?

Answer 1

Permanent cessation of menstruation
Loss of ovarian follicular activity
Usually occurs 45-55 yrs

Question 2

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

Answer 2

Climacteric period

Periods irregular until they completely stop

Question 3

State 6 symptoms of menopause.

Answer 3

Hot flushes  
Urogenital Atrophy (leads to dyspareunia – painful sex) 
Sleep disturbance  
Decreased libido  
Depression  
Joint pain

Question 4

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

Answer 4

Oestradiol + Inhibin B

Question 5

How does feedback on the HPG axis change in menopause?

Answer 5

There is a loss of ovarian follicular activity, so production of oestradiol+ inhibin is reduced
Results in less negative feedback on the HPG axis
LH + FSH rise

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 + inhibin production

Question 7

What are the main complications of menopause?

Answer 7

Osteoporosis (protective effect of oestrogen on bone is lost, loss of bone matrix, 10-fold increased risk of fracture) 
Cardiovascular disease (women are protected against CVD 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

Question 9

How is the risk of endometrial cancer when taking oestrogen prevented?

Answer 9

Combine with progesterone

Progesterone 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 no endometrium to stimulate with oestrogen

Question 11

Describe the 2 different formulations of HRT.

Answer 11

Cyclical: take oestradiol every day + progesterone for the last 12-14 days
Combined continuous: take a little oestrogen + progesterone every day

Question 12

State 4 different types of oestrogen preparations.

Answer 12

Oral oestradiol (1 mg)
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 (1st pass) so bioavailability is very low.
Thus, in oral preparations, a high dose of oestradiol is required

Question 14

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

Answer 14

Ethinyl oestradiol

Ethinyl group protects the drug from hepatic 1st 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

HRT: giving a little bit of oestrogen to prevent symptoms of menopause.
Contraception: trying to suppress HPG axis so give a more potent type of oestrogen.

Question 16

State 5 side-effect/risks of HRT.

Answer 16

Breast cancer 
Coronary heart disease 
Deep vein thrombosis
Stroke  
Gallstones

Question 17

How does HRT affect cardiovascular disease risk?

Answer 17

Increased risk of CHD
Dependent on timing of exposure– older patients who are started on HRT have an increased risk of CHD but in younger women there is no increased risk

Question 18

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

Answer 18

Tibolone

Question 19

What is Tibolone used for and what are the risks?

Answer 19

Reduces risk of fracture

Increases risk of stroke

Question 20

What is raloxifene and how does it work?

Answer 20

It is a selective oestrogen receptor modulator (SERM)
Oestrogenic effects in bone: reduces risk of fracture
Anti-oestrogenic effects in breast + uterus: reduces risk of breast cancer

Question 21

What are the problems with raloxifene?

Answer 21

It is associated with an increased risk of fatal stroke + VTE
Does not reduce vasomotor symptoms

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 + 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 are 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

Thickens cervical mucus making it more difficult for sperm to penetrate

Question 29

When would you use the progesterone only pill?

Answer 29

If oestrogen is contraindicated –if there is an increased risk of thrombosis (oestrogen has pro-coagulant effects)
E.g. smoker, >35 yrs old, migraine with aura

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 due to its short half life + short duration of action

Question 31

What 3 things can you use for emergency contraception?

Answer 31

Copper IUD (up to 5 days): affects sperm viability + function + inhibits fertilisation)
Levonorgestral (within 72 hrs): high dose progesterone
Ulipristal (within 120 hrs): Anti-progestin activity, Delays ovulation by as much as 5 days, Impairs implantation

Question 32

What is the purpose of hormone replacement therapy?

Answer 32

Control vasomotor symptoms (hot flushes)

Question 33

What is the action of combined oral contraceptive pills?

Answer 33

Suppress ovulation via negative feedback actions of E + P at hypothalamus/ pituitary

Question 34

How is the pill taken?

Answer 34

Take for 21 days or 12 weeks

Stop for 7 days