Menopause Flashcards
What do the ovaries produce in reproductive years?
Estradiol, testosterone and androstenedione
What do the ovaries produce postmenopausally?
Androstenedione and testosterone (androgens then being converted by peripheral tissues into estrone)
What is the first and last hormone to be affected in menopause?
FIRST - FSH
LAST - oestradiol
How do circulating hormone levels differ in someone that is post-oopherectomy vs. postmenopausal?
People that have had a oopherectomy have far less testosterone and androstenedione
When should HRT be continued until?
At least until the natural average age of menopause (i.e. 51)
What proportion of older women have osteoporosis?
1 in 3
At what age is peak bone mass achieved?
25
What type of osteoporosis is more common in postmenopausal women?
Type 2
Type 2 affects men and women equally and in characterised by the loss of trabecular and cortical bone mass
What proportion of women will experience irregular bleeding within the first 3 months of using HRT?
80%
An ET of what, in a woman bleeding in the progesterone phase of sequential HRT, would warrant further investigation?
> 7mm
Where sinister causes of bleeding whilst on HRT have been excluded, what should be done?
Increase or change the type of progesterone
What is the mechanism of action of bisphosphonates in the treatment of oestrogen deficiency osteoporosis?
- Bind to the hydroxyapatite binding sites at the bone surface inhibiting their breakdown
- Also inhibit osteoclast mediated bone resorption
- May inhibit apoptosis of osteoblasts and osteocytes
When should progestogen only methods of contraception be used until?
Age 55
or
Check FSH levels - if FSH levels >30IU/L, can stop using contraception in 12 months
What is the most common cause of PMB?
Atrophic endometritis and vaginitis - accounts for 60-80% of cases
What type of progestogen may reduce the risk of VTE?
Micronised progesterone
How does osteoporosis occur in someone NOT using HRT?
An imbalance between osteoclastic and osteoblastic activity
Lack of oestrogen results in increased osteoclast activity, and therefore increased bone resorption
How does the bone structure change in osteoporosis?
- Fewer trabeculae
- Thinning of cortical bone
- Widening of hervasian canals
How should a low FRAX score be managed?
Lifestyle advice + HRT
How should a intermediate FRAX score be managed?
DEXA scan
How should a high FRAX score be managed?
Offer treatment
What are the possible DEXA scores?
+1 - -1 = normal
-1 - -2.5 = osteopenia
< -2.5 = osteoporosis
What dose of calcium/vit D should be offered as part of lifestyle management in relation to bone health?
Calcium 1000mg + Vit D 1000 IU
What is the definition of menopause?
12 months after last period
What is the burden of menopause Sx?
75% experience menopausal Sx,
25% describe severe Sx, 1/3rd experience long-term Sx
What proportion of women experience genitourinary Sx during menopause?
50%
Over what period do menopausal Sx last?
Median duration= 7 years
20% of women = Sx up to 15 years
What is the average age of early peri-menopause?
47
What is the average age of late peri-menopause?
49
What are the most common menopausal Sx?
Hot flushes and night sweats - 70-80%
When >45 y/o, which diagnoses can be made without laboratory testing?
Perimenopause - based on vasomotor symptoms and irregular periods
Menopause - not had a period for at least 12 months and are not using hormonal contraception
Menopause - based on symptoms in women w/out a uterus
In whom may an FSH be used to aid diagnosis of menopause?
Women aged 40-45 y/o with menopausal Sx, INCLUDING a change in their menstrual cycle
Women <40 y/o in whom menopause (POI) is suspected
What proportion of women may experience menopause between the ages of 40-45?
5%
In whom should FSH NOT be used to diagnose menopause?
Women using CHC or high-dose progestogen
At what age is menopause considered premature/diagnosis of premature ovarian insufficiency?
<40 y/o
What is happening physiologically in the perimenopause?
Fewer functional follicles
Cycles often anovulatory as follicles not responsive enough to LH and FSH
This causes irregular periods
Less oestrogen from granulosa
Less progesterone – leads to increased GNRH, LH and FSH but more erratic
Decreased inhibin B – less negative feedback on pituitary
What proportion of cases of premature ovarian insufficiency are idiopathic?
85-90%
What proportion fo POI are genetic?
10-13%
What are the genetic causes of POI?
- Turner’s syndrome - test someone for if presenting at <30y/o with POI
- BRCA1
- Fragile X
How is POI diagnosed?
<40 y/o
AND
Menopausal symptoms, including no or infrequent periods
AND
x2 FSH >30 (>40 BMS) on two occasions, 4-6 weeks apart
What is the spontaneous conception rate with POI?
5%
What treatment options should be offered to women with POI (because of the osteoporosis or cardiovascular risk)?
Either HRT or a CHC, and continue until at least the age of natural menopause
What is the effect of menopause on the urogenital tract?
Oestrogen stimulates exfoliation of vaginal epithelial cells, causing increased levels of glycogen which theLactobacilliconvert to lactic acid. Creates an acidic environment with a pH of 3.5to 5.0, which the lactobacilli continue to thrive and protect from vaginal and urinary tract infections. Without it, the risk of infection increases
Lack of oestrogen also results in reduced vascularity = thinning/dryness/atrophy
When is the VTE risk highest after starting HRT?
First 12 months, and not with transdermal preparations
Is the risk of CVD/stroke increased with the use of HRT?
Not if started before the age of 60 y/o, a small increase if started at >60y/o
How many extra breast cancer cases are there as a result of HRT?
3-4 per 1000 extra
BG rate = 13/1000. Extra 20 cases for combined HRT for 5 years. Only 5 extra cases for oestrogen only HRT
What are the indications for transdermal HRT therapy?
Individual preference
Poor Sx control with oral
GI disorder affecting oral absorption
Previous or family Hx of VTE
BMI >30
Variable blood pressure control
Migraine
Current use of hepatic inducing enzymes medication
Gall bladder disease
What are the herbal remedies that may be used to relive vasomotor Sx (discussed by NICE)?
Isoflavones
Black cohosh
When does HRT have no effect on a woman’s cardiovascular risk?
When HRT is started in women aged <60 y/o
What are the 4 types of natural oestrogen?
Estrone - E1
Estradiol - E2
Estriol - E3
Esterol - E4
What are the characteristics of Estrone E1?
Present post-menopause
Produced by the adrenal glands and adipose tissue
10x less potent than E2
Used in conjugated equine estrogen
What are the characteristics of Estradiol E2?
Present in reproductive years
Produced by granulose cells in the ovaries
Most potent form of oestrogen
Used in oral and transdermal HRT
What are the characteristics of Estriol E3?
Present in pregnancy
Produced by the placenta
100x less potent than E2
Present in HRT creams
What are the characteristics of Esterol E4?
Present in pregnancy
Produced by the fetal liver during pregnancy
What are the different types of oral oestrogen?
- Conjugated equine - E1
- Estradiol 17 beta - E2
- Estradiol valerate - E2
What do oral oestrogens become and why?
All are metabolised to ESTRONE, as they go though first pass metabolism. Because estrone is much less potent, higher doses are required
What type of oestrogen can also be used as a patch/gel/spray?
Estradiol 17 beta
Why is estradiol in the form of patches/gels/sprays also absorbed as estradiol
Because it avoids 1st pass metabolism
What is the half-life of estradiol 17 beta?
Half life 10-16 hours
What is the half-life of estradiol valerate?
Half life 27 hours
What are the characteristics of equine estrogens?
- Synthetic
- Conjugated forms of oestrogen
- Becomes estrone sulfate and equilline sulfate
- More potent than the ‘natural oestrogens’
What is the half life of micronised progesterone?
Half life 17 hours
Maximum serum concentration in 2.2 hours
How should micronised progesterone be used?
Taken at night with food:
- Increases bioavailability
- S/E occur overnight rather than in day
- Also acts as a mild sedative
What type of progestogen….?
Ethinyodialdioacetate
C19 TESTOSTERONE
What type of progestogen….?
Norethisterone
C19 TESTOSTERONE
What type of progestogen….?
Norethynodrel
C19 TESTOSTERONE
What type of progestogen….?
Norgestimate
C19 TESTOSTERONE
What type of progestogen….?
Levonergestrel
C19 TESTOSTERONE
What type of progestogen….?
Desogestrel
C19 TESTOSTERONE
What type of progestogen….?
Etonogestrel
C19 TESTOSTERONE
What type of progestogen….?
Getsodene
C19 TESTOSTERONE
What type of progestogen….?
Dienogest
C19 TESTOSTERONE
What type of progestogen….?
Norelgestromin
C19 TESTOSTERONE
What type of progestogen….?
Nomestrol
C19 TESTOSTERONE
What type of progestogen….?
Medoxyprogesterone acetate
C21 PROGESTERONE
What type of progestogen….?
Chlormadinone acetate
C21 PROGESTERONE
What type of progestogen….?
Cyprotone acetate
C21 PROGESTERONE
What type of progestogen….?
Nestorone
C21 PROGESTERONE
When should HRT be reviewed?
On commencing or changing dose - at 3 months
Once established - annually
How long before testosterone for HRT likely to have an effect?
3-6 months
How should testosterone therapy be monitored in HRT?
- Testosterone level pre-treatment to ensure not in the upper range to start
- Re-test at 3-6 weeks
- Monitor every 6-12 months
What is the start dosing of testosterone for HRT?
5mg
What are the absolute contraindications to HRT?
Acute VTE
Hepatic disorders
Undiagnosed vaginal bleeding
What is the association of breast cancer with HRT?
Probably slightly increased after a minimum of 5 years’ use of combined HRT, over the age of 50—
additional 3-4 cases per 1,000 women
Risk associated with
Oestrogen alone is very much less
Mortality is not increased
What factors are associated with a higher risk of breast cancer compared to HRT?
Postmenopausal obesity or >/= 2 units alcohol per day
What sort of bleeding problems with HRT should be referred for secondary assessment?
Sequential HRT — if increase in heaviness or
duration of bleeding, or if bleeding irregular
Continuous combined — if bleeding >6/12 of therapy, or if occurs after
spell of amenorrhoea
What side effects occur as a result of estrogen?
- Fluid retention
- Breast tenderness
- Bloating
- Nausea / Dyspepsia
- Headaches
What side effects occur as a result of progestogen?
- Fluid retention
- Breast tenderness
- Headaches
- Mood swings
- PMT-like symptoms
For how many days per month should women receive progestogen on a sequential regime?
12-14 days
When should years of HRT exposure be counted from in those with POI?
From age of 50 - NOT when HRT started
When may women with BRCA mutations use HRT?
When they have had a prophylactic oophorectomy - here add-back HRT can be used for
Sx Mx until 50y/o as this has not been associated with an increased risk of
breast cancer Dx
After 50, lifestyle changes and non-hormonal alternatives should be used
In women whom have had breast cancer, and who are taking tamoxifen, which SSRIs should NOT be used?
Paroxetine and fluoxetine - risk of reduction in HRT efficacy
What are the pros/cons of gabapentin in menopause?
PROs - reduces hot flushes at 900mg/day in 50%; improved sleep
CONs - weight gain, dry mouth, dizziness, drowsiness
What are the pros/cons of pregabalin in menopause?
PROs - similar baseline improvement in hot flushes as gabapentin
CONs - similar S/Es as gabapentin, but less marked and so often better tolerated
What are the pros/cons of clonidine in menopause?
PROs - reduction (?how much) in hot flushes; may complement anti-HTN medication
CONs - not for use in those with hypotension; sleep disturbance in 50% pts
What are the pros/cons of SSRIs in menopause?
PROs - improvement in hot flushes - variable (greatest baseline improvement with paroxetine - 50-60%, maximal benefit with 10mg); improved with QoL as with SSRIs
CONs - initial S/Es such as nausea, dizziness, short-term aggravation of base-line anxiety and mood, sexual dysfunction
What are pros/cons of venlafaxine (SNRI)?
PROs - baseline improvement of 20-66%; improved QoL
CONs - often poorly tolerated at outset with
dizziness and sexual dysfunction
What should be tested for prior to initiating testosterone therapy as part of HRT?
Total testosterone level (to establish not in the upper range before even initiating therapy)
When should F/U testing take place in relation to total testosterone level, after having started testosterone therapy?
IDEALLY 3-6 weeks, but practically most NHS clinics will re: test at 2-3 months
Ongoing monitoring should continue 6-12 monthly
What is a more accurate representation of therapeutic response to testosterone - total testosterone; free androgen index or free testosterone?
Total testosterone
When may SHBG level be useful in assessing therapeutic response to testosterone therapy?
Where SHBG levels are high e.g. due to high dose oral estrogen therapy, especially conjugated estrogens. This may explain lack of therapeutic response to physiological
testosterone replacement, despite normal total testosterone levels
When SHBG levels are very low, this may explain why androgenic adverse effects with testosterone replacement have occurred, despite normal total testosterone levels
What is the average weight gain in the perimenopause?
1.5kg per year in the perimenopause, leading to 10kg gain by menopause
To what degree does visceral fat increase in the perimenopause / menopause?
Visceral fat going from 5-8% total body weight, to 10-15% total body weight
What type of HRT is recommended for women undergoing a surgical menopause for endometriosis?
Continued combined oestrogen/progesterone HRT to reduce the risk of stimulation and malignant transformation
of endometrial deposits
Changing to estrogen only at a later date due to a better safety profile can be considered but must
be balanced with the risk of reactivating disease
HRT should be reviewed and suspended if symptoms recur
