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Year 2 - LCRS - Endocrinology > Contraceptives, HRT and SERMs > Flashcards

Contraceptives, HRT and SERMs Flashcards

21.10.2019

1
Q

What is menopause?

A
  • permanent cessation of menstruation

- loss of ovarian follicular activity

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2
Q

What is the average age menopause occurs in?

A
  • 51

- between 45-55

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3
Q

Climacteric

A
  • period of transition period
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4
Q

Symptoms of menopause

A
  • hot flushes (head, neck, upper chest)
  • urogenital atrophy & dyspareunia
  • sleep disturbance
  • loss of libido
  • joint pain

-> symptoms usually diminish/disappear with time

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5
Q

Dyspareunia

A

painful sex

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6
Q

What is the normal HPG axis?

A
  • pulsatile GnRH from the hypothalamus
  • stimulates release of LH and FSH from the anterior pituitary
  • stimulates oestradiol / inhibin production and secretion in the ovaries
  • oestradiol and inhibin negatively feed back to the hypothalamus and AP
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7
Q

How is the HPG axis different in menopause?

A

Loss of ovarian follicular activity (depletion?) leads to:

  • no oestradiol and inhibin production -> low oestradiol
  • no negative feedback -> high LH and FSH
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8
Q

What are some complications of menopause?

A
  • osteoporosis (oestrogen deficiency, loss of bine matrix, 10x increased risk of fracture)
  • Cardiovascular disease (protected before menopause, same risk as men at age 70)
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9
Q

What is an important effect of HRT?

A
  • controls vasomotor symptoms (hot flushes)
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10
Q

What are the effects of oestrogen in HRT?

A
  • causes proliferation of the endometrium

- risk of endometrial carcinoma

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11
Q

What are the effects of progestogens in HRT?

A
  • protect from increased risk of endometrial cancer
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12
Q

Which women would oestrogen-only HRT be recommended for?

A
  • women post hysterectomy (basically no risk of endometrial cancer)
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13
Q

Why is E+P HRT generally prescribed?

A
  • to prevent endometrial hyperplasia
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14
Q

What are the two main HRT formulations?

A
  • Cyclical: E (every day) + P (12-14 days) (add P for 12-14d)
  • Continuous combined
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15
Q

What are the different ways of administering oestrogen preparations?

A
  • Oral estradiol (1mg)
  • Oral conjugated equine oestrogen (0.625 mg)
  • Transdermal (patch) oestradiol (50 microgram/day)
  • Intravaginal
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16
Q

Oestrogens - pharmacology

A
  • very well absorbed
  • low bioavailability due to 1. pass metabolism
  • groups can be added e.g. ethinyl estradiol or estrone sulphate
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17
Q

Estrone sulfate

A

“conjugated” oestrogen

18
Q

Ethinyl estradiol

A
  • The ethinyl group protects the molecule from first pass metabolism
  • semi-synthetic oestrogen
  • found in oral contraceptive pills
19
Q

How can most oestrogen preparations be administered?

A
  • orally

- via transdermal skin patches

20
Q

What are the side effects of HRT?

A
  • Breast cancer
  • Coronary heart disease
  • Deep Vein thrombosis
  • Stroke
  • Gallstones
21
Q

Absolute risk of HRT?

A

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

22
Q

HRT and risk of CHD

A
  • timing of exposure is important!!
  • no excess CVD risk in younger menopausal women
  • in younger women oestrogen is protective
  • in older women with established atherosclerosis it is
23
Q

Why does O only decrease but E+P increase the risk of CHD?

A
  • synthetic progestins negate the protective effects of oestrogen
24
Q

What are the effects of oestrogen on CHD?

A
  • beneficial effects on lipid profile & endothelial function
25
Q

Why is oestrogen harmful with regards to CHD in women >60 years of age?

A
  • they probably have atherosclerosis

- are susceptible to prothrombotic & proinflammatory effects of oestrogen

26
Q

Tibolone

A
  • Synthetic prohormone
  • Oestrogenic, progestogenic & weak androgenic actions
  • Reduces fracture risk
  • Increased risk of stroke (RR: 2.2)
  • ? increased risk of Breast Ca
27
Q

SERM

A

selective oestrogen receptor modulator

e.g. Raloxifene

28
Q

Raloxifene

A
  • Oestrogenic in bone: reduces risk of vertebral fractures
  • Anti-oestrogenic in breast & uterus: reduces breast cancer risk
  • Does not reduced vasomotor symptoms
  • increased risk of VTE & fatal stroke
29
Q

Tamoxifen

A
  • anti-oestrogenic in breast tissue

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

30
Q

Premature ovarian insufficiency

A

Menopause occurring before the age of 40

31
Q

What fraction of women are affected by premature ovarian insufficiency?

A

1%

32
Q

What are the causes of premature ovarian insufficiency?

A
  • chemotherapy
  • radiation
  • surgery
  • autoimmune
33
Q

What is in the combined oral contraceptive pill?

A

Oestrogen (ethinyl oestradiol) + Progestogen (e.g. levonorgestrel or norethisterone)

34
Q

How does the oral contraceptive pill work?

A
  • Suppress ovulation:
  • E&P: negative feedback actions at hypothalamus/pituitary
  • P thickens cervical mucus
35
Q

Administration of COCP

A

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

36
Q

When would you give a progesterone only contraceptive pill?

A
  • in smokers
  • > 35 years of age
  • migraine with aura
  • people with increased risk of thrombosis?
37
Q

Administration of progesterone only oral contraceptive pill

A

Must be taken at the same time each day

  • Short half-life
  • Short duration of action

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

38
Q

Name examples of emergency (post coital) contraception

A
  • copper IUD
  • levonorgestrel
  • Ulipristal
39
Q

Copper IUD

A
  • exclude pregnancy first
  • affects sperm viability and function
  • Effectiveness not reduced in overweight/obese women
  • 5 (up to 7) days after unprotected intercourse
40
Q

Levonorgestrel

A
  • efficiency reduces with time so take ASAP after unprotected sex
  • within 72 hours!!
41
Q

Ulipristal

A
  • up to 120h after intercourse
  • Anti-progestin activity
  • delay ovulation by as much as 5 days
  • Impairs implantation

Year 2 - LCRS - Endocrinology (18 decks)

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