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Endocrinology year 2 > Menopause, HRT and oral contraceptive > Flashcards

Menopause, HRT and oral contraceptive Flashcards

1
Q

Why can’t we measure GnRH

A

It’s not in the peripheral circulation

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2
Q

What is a common symptom of menopause

A

Sleep Disturbance

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3
Q

What may be some of the patient worries regarding HRT and menopause

A 
Bones- damaging effects of menopause on the bone (loss of bone density)
Breast cancer (side effects of HRT)
‘Blood clots in the leg’
Stroke
‘Heart attack’- CVS effects of HRT
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4
Q

Define menopause

A

Permanent cessation of menstruation
Loss of ovarian follicular activity
They stop making estradiol

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5
Q

What are the key features of menopause

A

Average age 51 (range 45-55)

Climacteric: period of transition period- periods become irregular until they eventually stop.

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6
Q

How do some women view menopause

A

This is a natural process of life.

The body at the beginning will get a bit mad.

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7
Q

Describe the eventual transition to menopause

A

Climacteric period

You go from having normal regular cycles and then it becomes a little irregular (oligomenorrhoea) and then it progresses to amenorrhoea.
Permanent cessation of menstruation - amenorrhoea for more than 12 months

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8
Q

State the symptoms of menopause

A 
Hot flushes (head, neck, upper chest)
Urogenital atrophy & dyspareunia (pain having sexual intercourse)

Sleep disturbance
Depression
Decreased libido
Joint pain

Symptoms usually diminish/disappear with time.

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9
Q

What do the ovaries produce that has feedback on the HPG axis

A

Oestradiol and Inhibin B

Negative feedback at the level of the anterior pituitary and the hypothalamus.

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10
Q

Describe the hormonal changes in menopause

A

The ovaries no longer produce estradiol and inhibin B
Hence, less negative feedback on the anterior pituitary and the hypothalamus
High GnRH, high LH and high FSH.

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11
Q

Describe how oesteoporosis is a key complication of menopause

A

Oestrogen deficiency
Loss of bone matrix
10-fold increased risk of fracture
§ Loss of 1-3% of bone mass/year and have 10x increase risk of fracture.

Lose anabolic effects of oestrogen on bone (via osteoblasts).

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12
Q

Describe cardiovascular disease as a key complication of menopause

A

protected against CVD before the menopause

have the same risk as men by the age of 70

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13
Q

What is the key aim of HRT

A

Control vasomotor symptoms (hot flushes) - which are very problematic for paitents- major disruption to their life.

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14
Q

Summarise the basis of HRT that should be given to post-menopausal women

A

Oestrogen (E):
endometrial proliferation
risk of endometrial carcinoma

Progestogens (P)- sheds endometrial lining- thus reducing the risk of endometrial cancer

HRT: E + P to prevent endometrial hyperplasia

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15
Q

Describe the basis of HRT is the woman has had a hysterectomy

A

(If hysterectomy: E only)

No endometrium, thus no risk of endometrial cancer.

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16
Q

Describe two common HRT formulations

A

can be cyclical, with oestrogen daily and progesterone every two weeks, or continuous combined

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17
Q

Describe the different oestrogen preparations

A

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

18
Q

Describe the absorption and metabolism of estradiol

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 oestradio

19
Q

Describe some different preparations of estradiol

A

Estrone sulphate (‘conjugated’ oestrogen)

Ethinyl estradiol :a semi-synthetic oestrogen
The ethinyl group protects the molecule from first pass metabolism- core part or oral contraceptives.

20
Q

What can most oestrogens be administered as

A

Most oestrogens can also be administered via transdermal skin patches

21
Q

State some of the side effects of HRT

A 
Breast cancer
Coronary heart disease
Deep Vein thrombosis
Stroke
Gallstones
22
Q

What is the key difference between the doses of oestrogen given in HRT and the doses in oral contraceptives

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.

23
Q

What is important to remember regarding the absolute risk of HRT complications

A

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

24
Q

What are the take home messages form the WHI trials

A

Increased risk of CHD events!
19 additional events/yr per 10,000 women

Mean age: 63 years

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

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

25
Q

Describe and explain the results from the WHI trials

A 
Additional cases per 1000 women (compared to oestrogen alone)
taking combined  (E+P) HRT for 5 years:

Breast cancer (invasive): 3
CHD: 2.5
DVT: 5
Stroke: 2.5

However both are protective against all cause mortality.

When you are young:
Oestrogen:
beneficial effects on lipid profile &
endothelial function

Synthetic progestins:
Negate these effects of estrogen

Over 60
 Atherosclerosis
 Susceptible to prothrombotic &amp; 
proinflammatory effects of oestrogen
Hence the increased risk of CHD in this study.
26
Q

Describe tiobolone

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

Which property of oestrogen receptors do SERMs exploit

A

They have different structures at different sites in the body- allowing SERMs to have agonistic effects at some sites, but antagonistic effects at other sites.

28
Q

Describe raloxifene

A

Selective oestrogen receptor modulator
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

What is tamoxifen

A

Anti-oestrogenic on breast tissue

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

But Oestrogenic effects on bone

30
Q

Summarise premature ovarian insufficiency

A

Menopause occurring before the age of 40
1% of women

Autoimmune
Surgery
Chemotherapy
Radiation

The last 3 are iatrogenic

31
Q

When is raloxifene used

A

Used for treatment & prevention of postmenopausal osteoporosis

32
Q

Describe the absorption and metabolism of progestogerones

A

Progesterone is poorly absorbed and rapidly metabolised in the liver.
Progesterone can be given by intramuscular injection as a depot preparation.
A variety of orally active synthetic progestogens are available e.g. norethisterone.

33
Q

Describe combined oral contraceptives

A

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

Suppress ovulation:
E&P: negative feedback actions at hypothalamus/pituitary
P thickens cervical mucus (makes it harder for sperm to fertilise the egg)

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

34
Q

Describe the key features of combined oral contraceptives

A

Combination of an oestrogen (ethinyl oestradiol) and a progestogen (e.g. levonorgestrel or norethisterone) provides synergistic pharmacology to suppress ovulation via multiple mechanisms:
E upregulates P receptors.
E counteracts the androgenic effects of synthetic P

35
Q

What is the effect of oestrogen on weight

A

Increased weight (water retention and fat deposition)

36
Q

When is the progesterone only contraceptive indicated

A

When oestrogens contra-indicated
smoker, > 35 yrs old, migraine with aura
e.g. CVS problems, history of thrombosis, prior to major surgery, during lactation (oestrogen should be low during lactation).

37
Q

When should progesterone only contraceptives be given

A

Must be taken at the same time each day
Short half-life
Short duration of action

38
Q

Describe some longer-lasting preparations of progesterones

A

Long acting preparations may be given by deep intramuscular injection (e.g. medroxyprogesterone acetate/Depot-Provera) or via an intra-uterine system (Mirena)
Oral (‘POP’) preparations -progersterone only pill

39
Q

Describe the morning after pill

A

Combined E & P or P only (levonorgestrel)
2 doses 12 hours apart, beginning as soon as possible within 72 hours of intercourse; single one-step double strength tablet also available.
May cause nausea and vomiting

40
Q

Describe copper IUD as emergency contraception

A

Copper IUD (intrauterine contraceptive device)
exclude pregnancy first
affects sperm viability and function- thus preventing fertilisation
Effectiveness not reduced in overweight/obese women
5 (up to 7) days after unprotected intercourse

41
Q

Describe urilipristal as emergency contraception

A

(up to 120 hours after intercourse)
Anti-progestin activity
delay ovulation by as much as 5 days
Impairs implantation

Endocrinology year 2 (13 decks)

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