Endo 10: HRT, menopause and oral contraceptives Flashcards

1
Q

Define menopause

A
  • Permanent cessation of menstruation
  • Loss of ovarian follicular activity

CLIMACTERIRIC= period of transition

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2
Q

Average age of menopause

A

51 (45-55)

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3
Q

Complications of menopause (note that these are NOT symptoms!)

A

Osteoporosis, due to oestrogen deficiency, loss of bone structure and 10X more risk of fracture (oestrogen is an anabolic hormone)

CVD- protected until menopause, after have the same risk as men by age 70

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4
Q

Menopause symptoms

A
  • Hot flushes (head, neck, upper chest)
  • Urogenital atrophy & dyspareunia (=painful sexual intercourse )
  • Sleep disturbance
  • Depression
  • Decreased libido
  • Joint pain

Diminish with time

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5
Q

What is the problem with only giving oestrogen

What is usually given in HRT

When could oestrogen only be given in HRT

A

Causes endometrial proliferation

Risk of endometrial carcinoma

HRT: oestrogen and progesterone (reduces endometrial hyperplasia)

Oestrogen only in hysterectomy

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6
Q

Outline the hormonal changes in menopause

A

Cessation of ovarian function, less oestradiol and inhibin B produced, so less negative feedback on pituitary and hypothalamus so increase GnRH and thus LH and FSH

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7
Q

Where is inhibin B produced

A

FSH stimulates the secretion of inhibin from the granulosa cells of the ovarian follicles in the ovaries. In turn, inhibin suppresses FSH

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8
Q

What is the point of HRT

A

To control the vasomotor symptoms (flushes)

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9
Q

What will patients usually be given if they have not had a hysterectomy at menopause

A

Eostrogen and progesterone (to prevent endometrial hyperplasia)….

Remember, in endometrial cycle, oestrogen causes the PROLIFERATIVE stage, and progesterone causes the SECRETORY stage

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10
Q

Differentiate cyclic and continuous combined HRT formulations

A
Continous combined (both e and p continuously) 
Cyclic- oestrogen every day and p every 12-14 days
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11
Q

Different oestrogen preparations for HRT

A

Oral estradiol
Oral conjugated equine oestrogen
Transdermal patch
Intravaginal

patch dose much lower than others

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12
Q

What does ‘conjugated’ oestrogen mean

A

Oestrogen conjugated to sulphur

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13
Q

What is bioavailability of oestrogen

A

Low (good absorption but high 1st pass metabolism)

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14
Q

Special feature of ethinyl oestradiol

A

Ethinyl group protect molecule from first pass metaolsim

ALSO A CONTRACEPTIVE

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15
Q

Side effects of HRT

A

Think BCD:
Breast cancer
Coronary heart disease
Deep vein thrombosis

Stroke
Gall stones

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16
Q

Risk of taking HRT for 5 years for woman in 50s for CHD

A

VERY LOW,

Risk increases for women over 60 because they have atherosclerosis already. In these patients…. more CHD events

Be mindful of risk factors still

17
Q

Differentiate the use of ethinyl oestradiol in contraception vs in menopause

A

In HRT you are giving bit of oestrogen to reduce symptoms,

In contraception you give to suppress HPG axis so you get less FSH and LH

18
Q

Outline tibolone

A

Used for HRT (not contraception)

Tib sounds like fib, and this is a fib as it’s

Not an oestrogen,

It has oestrogenic, progestogenic and androgenic effects

Reduces fracture

Increases stroke (2.2X), possible breast cancer

19
Q

Outline ramoxifen

A

It is a SERM

Selective estrogenic receptor modulator….

In bone it is oestrogenic (so increases bone strength)

In breast and uterus anti-oestrogenic so reduces breast cancer risk

But increases stroke risk and VTE

20
Q

How does tamoxifen work what is it used to treat

A

Antioestrogenic on breast… used to treat oestrogen dependent breast tumours and metastatic breast cancer

(T for tits, treats breast cancer)

21
Q

What is premature ovarian insufficiency

A

Menopause before aged 40…. 1% of women

22
Q

Causes of premature ovarian insufficiency

A

Autoimmune
Chemotherapy
Radiation
Surgery

23
Q

How is combined oral contraceptive given (i.e how do they use)

A

Take for 21 days stop for 7

24
Q

What is in combined oral contraceptiopon

A

Eostrogen (ethinyl oestradiol) and progestogen (levonorgestrel or norethisterone)

Remember that it’s ethinyl oestradiol as this doesn’t undergo extensive first pass metabolism

25
Q

How do combined oral contraceptives work

A

SUPPRESS OVULATION:

Giving high oestrogen and progestogens will have negative feedback to reduce FSH and LH release.

Progesterone will also thicken the cervical mucus so less likely for sperm to get to the egg

26
Q

When to give progestogen only contraceptive and why

A

When oestrogen contraindicated: smoker, over 35, migraine with aura

Because, even though they are not over 60, they are going to have massively increased risk factors for atherosclerosis already and oestrogen will increase this (it’s pro-inflammatory/prothrombotic in the case of atherosclerosis)

27
Q

How are progesterone only contraceptives taken

A

Same time every day (they have short half life, short duration of action)
or
Intrauterine for long acting prep (mirena coil)

28
Q

What are the conditions for giving copper IUD.

How does it work

Is its effectiveness reduced in overweight or obese women

How long after sexual ntercourse is it effective for

A

This is emergency contracpetion (POST COITAL)….. intrauterine contraceptive device….

exclude other pregnancy first

it affects sperm viability and function

Effectiveness not reduced in overweight/obese women
5 (up to 7) days after unprotected intercourse

e.g MIRENA

29
Q

Other than copper IUD, 2 other emergency contraceptives and when to take.

What is the problem with these

A

Levonorgestrel (within 72 hrs)- progestogen

Ulipristal (up to 120hrs)

Associated with reduced effectiveness in overweight patients

30
Q

How does ulipristal work

A

anti-progestin activity?????

Delay ovulation by 5 days
impair implanation

31
Q

How do the effects of oestrogen differ with age

A

In younger women ,taking oestrogen in HRT:
- has beneficial effects on lipid profile &endothelial function

Older women above 60 on HRT,
-Already have higher levels of atherosclerosis
-Susceptible to prothrombotic &
proinflammatory effects of oestrogen

32
Q

For younger women on HRT, why do they not see the beneficial effects of oestrogen when taking HRT

A

Because of the endometrial hyperplasia associated with HRT, they must it with progestins

The synthetic progestins negate the beneficial effects of oestrogen on CHD

33
Q

Outline the safety of HRT

A

Timing of exposure is important
No excess risk in younger menopausal women

Women < 10 years since menopause or 50-59 years: no excess risk

Older women (>60):
Atherosclerosis
Susceptible to prothrombotic &
proinflammatory effects of oestrogen

34
Q

Just the overall thing about oestrogen and progesterone

A

FOR HRT:

Don’t want to give oestrogen alone due to endometrial proliferation and cancer

Don’t want to give in over 60s because these already have atherosclerosis and oestrogen will be proinflammatory/pro-thrombotic in this case

In youner women (i.e. 50, or within 10 years of menopause), the atherosclerosis is not so bad. In younger people, oestrogen has positive effects on lipid profile and endothelial function. BUT the progestins negate these effects.

FOR CONTRACEPTION:
Again always give oestrogen with progesterone (combined) due to endometrial cancer risk

In women over 35 who have smoking/overweight etc. they are porbably going to be having higher atherosclerosis so giving oestrogen will be pro-inflammatory/pro-thrombotic in this case.

So you give progesterone only

Note…. in HRT, you are giving small dose of oestrogen (and progesterone to reduce proliferation risk) to reduce symptoms of flushing etc.

In contraception you are giving higher dose oesterogen/progesterone to negatively feedback on the pituitary/hypothalamus to be reducing LH and FSH and prevent pregnancy