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Y2 LCRS1 Endocrinology > Oral Contraceptives, Menopause and HRT > Flashcards

Oral Contraceptives, Menopause and HRT Flashcards

1
Q

What is menopause?

A

Permanent cessation of menstruation - amenorrhoea for more than 12 months
Loss of ovarian follicular activity
NOTE: usually happens between 45-55 yrs (avg age 51)

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2
Q

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

A

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

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3
Q

State some symptoms of menopause.

A 
Hot flushes  
Urogenital Atrophy (leads to dyspareunia – difficult or painful sexual intercourse)

Sleep disturbance
Decreased libido
Depression
Joint pain

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4
Q

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

A

Oestradiol and Inhibin B

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5
Q

How does this feedback change in menopause?

A

There is a loss of ovarian follicular activity –> decreased production of oestradiol and inhibin
–> less negative feedback on the HPG axis

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6
Q

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

A

High – because of the loss of oestrogen and inhibin production

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7
Q

What are the main complications of menopause?

A

Osteoporosis - oestrogen deficiency –> loss of bone matrix –> 10 fold increased risk of fracture
Cardiovascular disease - oestrogen protects women from CVD before menopause; women have the same risk of CVD as men by age 70

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8
Q

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

A

Endometrial proliferation –> increases the risk of endometrial carcinoma

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9
Q

How is the risks of giving pure oestrogen in HRT be prevented?

A

You give progesterone as well as oestrogen

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

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10
Q

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

A

Patients who have had a hysterectomy

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

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11
Q

Describe the 2 different formulations of HRT.

A
  1. Cyclical – take oestradiol every day and then for the last 12-14 days you take progesterone
  2. Combined continuous – take a little oestrogen and progesterone every day
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12
Q

State 4 different types of oestrogen preparations.

A

Oral oestradiol (1 mg)
Oral conjugated equine oestradiol (0.625 mg)
Transdermal oestradiol (50 mcg/day)
Intravaginal

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13
Q

Describe the absorption and metabolism of oestradiol.

A

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.

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14
Q

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

A

Ethinyl oestradiol

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

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15
Q

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

A

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.

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16
Q

State some side-effect/risks of HRT.

A 
Breast cancer  
Coronary heart disease
Deep vein thrombosis 
Stroke  
Gallstones

BCD

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17
Q

How does HRT affect cardiovascular disease risk?

A

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

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18
Q

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

A

Tibolone

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19
Q

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

A

It reduces the risk of fracture
It increases the risk of stroke
Possible increased risk of breast cancer

20
Q

What is raloxifene and how does it work?

A

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
21
Q

What are the problems with raloxifene?

A

It is associated with an increased risk of fatal stroke and VTE
It also DOES NOT reduce vasomotor symptoms

22
Q

What is tamoxifen?

A

Anti-oestrogenic on breast tissue

23
Q

What is tamoxifen used for?

A

Treatment of oestrogen-dependent breast tumours and metastatic breast cancers

24
Q

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

A

Premature Ovarian Insufficiency

Affects 1%

25
Q

What could POI be caused by?

A

Autoimmune
Surgery
Chemotherapy
Radiotherapy

26
Q

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

A

Ethinyl oestradiol

27
Q

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

A

Levonorgestral

Norethistrone

28
Q

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

A

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

29
Q

When would you use the progesterone only pill?

A

If oestrogen is contraindicated – smoker, >35 years old, migraines with aura, history of CVD (oestrogen has pro-coagulant effects)

30
Q

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

A

It must be taken at the same time every day

31
Q

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

A

Mirena

32
Q

What 3 things can you use for emergency (post-coital) contraception? What is the time frame?

A

Copper IUD (affects sperm viability and function and inhibits fertilisation)(up to 7 days after unprotected sex)
Levonorgestral (within 72 hours – high dose progesterone)
Ulipristal (within 120 hours)
= Anti-progestin activity
= Delays ovulation by as much as 5 days
= Impairs implantation

33
Q

Why is hormone replacement therapy given to menopausal women?

A

To control the vasomotor symptoms (hot flushes)

34
Q

Name 3 different types of oestrogens which can be given.

A

Oestradiol - well absorbed but low bioavailability due to first pass metabolism
Esterone sulphate - “conjugated” oestrogen
Ethinyl estradiol - seimi-synthetic oestrogen (ethinyl group protects the molecule from first pass metabolism)

35
Q

How can oestrogen preparations be administered.

A

Transdermal skin patches

36
Q

Why should oestrogen not be prescribed as first line treatment to older women?

A

They have more atherosclerosis

Susceptible to prothrombotic and proinflammatory effects of oestrogen

37
Q

Name three HRT drugs.

A

Raloxifene
Tibolone
Tamoxifen

38
Q

What does the combined contraceptive pill contain?

A

Oestrogen (ethinyl oestradiol)+

Progestogen (e.g. LEVONOrgestrel or norethisterone)

39
Q

How long is the combined pill taken for?

A

21 days (or 12 weeks) and stop for 7 days.

40
Q

Why must the progesterone only pill be taken at the same time each day?

A

It has a short half-life
Short duration of action

Long preparations can be given via intra-uterine system

41
Q

What are the advanatages of teh copper IUD?

A

Affects sperm viability and function
Effectiveness not reduced in overweight/obese women
5-7days after unprotected intercourse.

42
Q

True or False? Norethisterone:

  • is a progestogen
  • is a derivative of testosterone
  • is an oestrogen
  • is the principal component in the post-coital “emergency” contraceptive
  • is orally active
A 
True
True
False
False
True
43
Q

True or False? Ethinyl estradiol:

  • is orally active
  • stimulates proliferation of the endometrium
  • increases circulating triglycerides and high density lipoproteins
  • down-regulates progesterone receptors
  • thickens cervical mucus
A 
True
True
True
False
False

Response Feedback: Steroids (unlike peptides) are orally active, as they survive the GI tract. Plain oestradiol (17 beta) would not be active as it would be rapidly first pass metabolised. However having the ethinyl group on position 17 protects the molecule from first pass metabolism, which is why this is the principle component of many oral contraceptive

44
Q

Progestogen only contraceptives:

  • are superior in their contraceptive effects to the combined oral contraceptives
  • may be taken orally
  • may be administered by deep intramuscular injection
  • are contraindicated in nursing mothers
  • are preferable to estrogen-containing contraceptives in women with a history of deep vein thrombosis
A 
False
True
True
False
True
45
Q

The menopause:

  • does not affect the development of ovarian follicles
  • can be confirmed by detecting raised levels of LH in the circulation
  • can be associated with osteoporosis
  • is associated with increased protection from cardiovascular disease
  • is associated with a decline in serum oestrogens
A 
False
True
True
False
True
46
Q

Hormone replacement therapy:

  • Is not necessary for premature menopause
  • Can relieve symptoms associated with the menopause
  • Reduces the risk of hip fracture in post-menopausal women
  • Could be associated with a small increase in breast cancer risk
  • Needs to be continued through the patient’s lifetime to be effective
A 
False
True
True
True
False
47
Q

A 51 year old woman is suffering from Oligomenorrhoea and hot flushes that are diagnosed as the early stages of the menopause. She has previously had two children and no gynaecological surgery:

  • This is quite early to start the menopause
  • If she desires HRT oestrogen should be given alone
  • If she took HRT it would lower her risk of fracturing the neck of her femur
  • HRT is associated with an increased risk of cholecystitis
  • Her gonadotrophin levels are probably reduced
A 
False
False
True
True
False

Response Feedback:

  1. 51 years is the average age of menopause
  2. she must use oestrogen and progesterone to protect her endometrium from carcinoma
  3. Oestrogen reduces the risk of osteoporosis
  4. HRT increases the risk of cardiovascular disease
  5. they will be increased in the early stages of menopause due to reduced feedback of oestrogen

Y2 LCRS1 Endocrinology (18 decks)

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