Endocrinology 10 - Contraceptives, HRTs and SERMs

Question 1

What is menopause?

Answer 1

• Permanent cessation of menstruation
• Loss of ovarian follicular activity
• Average age 51 (range 45-55)

Question 2

List the symptoms of menopause

Answer 2

• Hot flushes (head, neck, upper chest)
• Urogenital atropy and dyspareunia (painful sex)
• Sleep disturbance
• Depression
• Joint pain
• Decreased libido

Question 3

What are the complications of menopause?

Answer 3

• Osteoporosis due to oestrogen deficiency (10 fold increased risk of fracture)
• Cardiovascular disease (same risk as men by age of 70, before menopause women are at lower risk)

Question 4

What are uses of HRT?

Answer 4

Control vasomotor symptoms of menopause (hot flushes)

Question 5

What are the two options for HRT administration

Answer 5

• Cyclical - oestrogen every day, progesterone 12-14 days

- Continuous combined

Question 6

Compare the different forms of oestrogen.

Answer 6

Oestrodiol

• Low bioavailability (due to first pass metabolism)
• Well absorbed
• Normal human oestrogen form

Estrone sulphate
- Conjugated oestrogen

Ethinyl estradiol

• Semi synthetic
• Ethinyl group protects from first pass metabolism

All can be administered as transdermal skin patches

Question 7

List the possible side effects of HRT

Answer 7

• Breast cancer
• Coronary heart disease
• Deep vein thrombosis
• Stroke
• Gallstones
• Absolute risk is very low

Question 8

What are the effects of oestrogen?

Answer 8

• In younger people oestrogen has beneficial effects on lipid profile and endothelial function
• In 60+ women with atherosclerosis, oestrogen will increase susceptibility to prothrombotic and proinflammatory effects. Therefore oestrogen increases risk of CHD in these women.

Question 9

What is tibolone?

Answer 9

• Synthetic prohormone
• Oestrogenic, progestogenic and weak androgenic
• Reduces fracture risk
• Increased stroke risk
• Might increase risk of breast cancer

Question 10

What is Raloxifene?

Answer 10

• Selective oEstrogen Receptor Modulator (SERM)
• Reduces risk of vertebral fractures
• Antioestrogenic in breast and uterus
• Reduces breast cancer risk
• Increased risk of VTE and stroke

Question 11

What is tamoxifen?

Answer 11

• Anti-oestrogenic on breast tissue

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

Question 12

What is premature ovarian insufficiency and what are its causes?

Answer 12

• Menopause before the age of 40 (1% of women)

- Can be caused by autoimmunity, surgery, chemotherapy or radiation

Question 13

What are combined oral contraceptives?

Answer 13

• Contain oestrogen (ethinyl oestradiol) and progestogen (levonorgestrel or norethisterone)
• Suppress ovulation (negative feedback actions and thickens mucous)
• Taken for 21 days with a 7 day break

Question 14

What are progesterone only contraceptives

Answer 14

• Used when oestrogens are contra-indicated (smoker, migraine with aura, over 35 years old)
• Taken at the same time every day (short half life and duration of action)
• May be given via inta-uterine system (long acting preparations)

Question 15

List the emergency post-coital contraceptions

Answer 15

• Copper IUD (exclude pregnancy first, affects sperm viability and function, can be used 5 days after unprotected intercourse)
• Levonorgesterel (72 hours)
• Ulipristal (120 hours after intercourse, anti-progestin, delays ovulation by 5 days and impairs implantation)

Question 16

How is menopause diagnosed?

Answer 16

• Measure LH, FSH and oestradiol

- Oestrodiol will be low, LH and FSH will be high due to loss of negative feedback

Question 17

Why does HRT contain both oestrogen and progesterone?

Answer 17

• Oestrogen causes endometrial proliferation, and therefore there is a risk of endometrial carcinoma
• Progesterone protects against increased risk of endometrial cancer
• If the patient has had a hysterectomy there is no need for progesterone

Question 18

Compare the risks of oestrogen alone to the combined oestrogen and progesterone when given to postmenopausal women 50-59 years of age

Answer 18

• Oestrogen alone is protective
• Increased breast cancer risk with combined E+P
• Synthetic progestins negate the effects of oestrogen

Question 19

What do selective oestrogen receptor modulators do?

Answer 19

• Have good effects in bones (oestrogenic effects)

- In the breast they are anti-oestrogenic, reducing breast cancer risk

Question 20

List the possible oestrogen preparations used in HRT

Answer 20

• Oral estradiol
• Oral conjugated equine (horse urine) oestrogen
• Transdermal patch oestradiol
• Intravaginal

Question 21

Define climacteric

Answer 21

The period of time where periods become irregular, and fertility starts to reduce (transition period before menopause)