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

Menopause, Contraceptives, HRT and SERMs Flashcards

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 of a patient experiencing menopause?

A

51 (45-55)

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3
Q

What is the climacteric period?

A

The climacteric period is a period leading up to the menopause where the patient experiences irregular periods

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4
Q

What are symptoms of menopause?

A
  • Hot flushes (head, neck, upper chest)
  • Urogenital atrophy and dyspareunia (painful sex, as a result of urogenital atrophy, very dry)
  • Sleep disturbance
  • Depression
  • Decreased libido
  • Joint pain
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5
Q

What happens to the symptoms of menopause, are they alleviated over time or with treatment?

A

Symptoms usually diminish/disappear over time

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6
Q

Describe and draw on paper the hypothalamo-pituitary-gonadal axis (HPG axis) in women.

A
  • Hypothalamus releases GnRH
  • GnRH stimulates pituitary to produce LH/FSH
  • LH/FSH stimulates ovaries to produce oestradiol and inhibin B
  • Oestradiol and inhibin B exert negative feedback on pituitary and hypothalamus release of LH/FSH and GnRH
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7
Q

How does the HPG axis differ during menopause?

A

Oestradiol and inhibin B production is stopped thus LH/FSH levels rise (GnRH rises as well)

No negative feedback now so production is no longer inhibited

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8
Q

What are the 2 main complications of menopause and what are their main features?

A

Osteoporosis

  • Oestrogen deficiency
  • Loss of bone matrix
  • 10-fold increased risk of fracture

Cardiovascular disease

  • Protected against CVD before the menopause due to oestrogen effects
  • Have the same risk as men by the age of 70 (risk rises with age)
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9
Q

What is the main reason HRT can be prescribed?

A

If the patient has disabling symptoms e.g. severe hot flushes

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10
Q

Why are oestrogen and progestogens given together in HRT?

A

Oestrogen causes:

  • endometrial proliferation
  • increases risk of endometrial carcinoma

Progestogens act to prevent endometrial hyperplasia
- thus preventing the potentially negative effects of the oestrogen alone from manifesting

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11
Q

What is the patient history that allows you to just give oestrogen replacement without progestogens?

A

If they have had a hysterectomy

- not worried about the possibility of endometrial cancer

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12
Q

What are the two types of HRT you can give?

A

Cyclical

Continuous combined

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13
Q

What is the rotation of hormone dose in cyclical HRT?

A

Oestrogen every day

Progestogens for 12-14 days

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14
Q

What are the 4 types of oestrogen replacement preparations?

A
  • Oral oestradiol
  • Oral conjugated equine oestrogen
  • Transdermal (patch) oestradiol
  • Intravaginal
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15
Q

How well is oestradiol is absorbed, what is its bioavailability and why?

A
  • Oestradiol is very well absorbed

- Low bioavailability because undergoes extensive first pass metabolism in the liver

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16
Q

What is an example of a ‘conjugated’ oestrogen replacement form?

A

Estrone sulphate

17
Q

What is ethinyl estradiol?

A

Ethinyl estradiol is a semi-synthetic oestrogen

- the ethinyl group protects the molecule from first pass metabolism, increases the bioavailability

18
Q

What administration method can most oestrogens by administered by?

A

Transdermal skin patch

19
Q

What negative effects does oestrogen have

A

Pro-thrombotic effects
Pro-inflammatory effects

Seen in older women because they have greater atherosclerosis whereas in younger women there is nowhere near the same degree of atheroma

20
Q

What are the side effects of HRT?

A
  • Breast cancer
  • Coronary heart disease
  • Deep vein thrombosis
  • Stroke
  • Gallstones

BCD are the main ones to remember

21
Q

How high is the absolute risk of complications for healthy symptomatic postmenopausal women in their 50s taking HRT for five years?

A

Very low absolute risk

22
Q

Who published a trial indicating HRT increases risk of of coronary heart diseae, what was the mean age, what is important in interpreting these results and what is the actual risk in younger menopausal women?

A

Women’s Health Initiative trials (WHI)

  • 19 additional events a year per 10000 women
  • mean age 63
  • Timing of exposure is important
  • No excess risk in women <10 years since menopause or 50-59 years
23
Q

What is the general trend of increase in risk in breast cancer, CHD, DVT, stroke after taking HRT for 5 years?

A

Additional cases per 1000 women

  • Breast cancer - 3
  • CHD - 2.5
  • DVT - 5
  • Stroke - 2.5
24
Q

What are the positive and negative effects in younger and older women (>60 yrs)?

A

Beneficial effects on lipid profile and endothelial function
- Synthetic progestins administered with the oestrogen negates the beneficial effects of the oestrogen

Older women (>60)

  • Atherosclerosis (or degree of)
  • susceptible to pro-thrombotic and pro-inflammatory effects of oestrogen
25
Q

What is Tibolone, what effects does it have, what beneficial effect does it have and what negative effects does it have?

A

Tibolone:

  • is a synthetic prohormone
  • has oestrogenic, progestogenic and weak androgenic actions
  • reduces fracture risk

Negatives

  • increased risk of stroke
  • possible increased risk of breast cancer
26
Q

What does SERM stand for?

A

Selective oEstrogen Receptor Modulator

- has different effects depending on the tissue in which the receptor it acts on is found

27
Q

What is Raloxifene, what effects does it have and where, and what are its negative effects?

A

SERM drug

  • Oestrogenic effects in bone, reduces risk of vertebral fractures
  • Anti-oestrogenic in breast and uterus, reduces cancer risk

Negative

  • does not reduce vasomotor symptoms (hot flushes/night sweats etc)
  • increased risk of VTE (venous thromboembolism) and fatal stroke
28
Q

What is tamoxifen, what effects does it have and where, and what is it used to treat?

A

Another SERM drug

  • Anti-oestrogenic on breast tissue
  • Used to treat oestrogen-dependent breast tumours and metastatic breast cancers
29
Q

What are the general “take-home messages” for HRT?

A

HRT is oestrogen + progesterone

  • prescribed
  • not used as first-line treatment for osteoporosis as we have other good treatments with fewer side effects
  • readily used in patients <60
  • not used in patients with history of ischaemic heart disease, coronary disease, DVT etc
  • not used in patients >60
30
Q

What is premature ovarian insufficiency, what % of women does it occur in, and what are the 4 areas of cause?

A

Menopause occurring before the age of 40
- 1% women

Causes

  • Autoimmune
  • Surgery
  • Chemotherapy
  • Radiation
31
Q

What two ingredients are found in the combined oral contraceptive pill?

A

Oestrogen (ethinyl oestradiol)

Progestogen (e.g. levonorgestrel or norethisterone)

32
Q

What are the aims and effects of the combined pill?

A

Both oestrogen and progestogens have negative feedback action at hypothalamus and pituitary

  • Progestogens ticken cervical mucus
  • Prevent conception/pregnancy is main goal
33
Q

What is the standard course of taking the pill?

A

21 days (or 12 weeks) taking pill then 7 days not taking it

34
Q

When is a progesterone-only contraceptive used?

A

When oestrogens contra-indicated

  • smoker
  • > 35 yrs old
  • migraine with aura
35
Q

When must the pill be taken from day to day and why is it so strict?

A

Must be taken at the same time every day

- short half-life and short duration of action so very little room for error in taking it

36
Q

How can long-acting preparations of progesterone-only contraceptive be administered?

A

Intra-uterine system

- Coil (Mirena coil)

37
Q

What are the 3 emergency (post-coital) contraceptive options?

A

Copper IUD (intrauterine contraceptive device)

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

Levonorgestrel (within 72 hours)

Ulipristal (up to 120 hours after intercourse)

  • anti-progestin activity
  • delay ovulation by as much as 5 days
  • impairs implantation

All in general

38
Q

Which emergency contraceptive is preferred in overweight/obese women and why?

A

Copper IUD

  • effectiveness unaffected by weight/body mass
  • other methods ARE affected by weight/body mass

LCRS Year 2 - Endocrinology (21 decks)

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