Menopause Flashcards
Sandrena gel
systemic HRT, E only
0.5mg/1mg
RF for earlier menopause
early menarche
smoking
Down’s
Developed country
nulliparity
high altitude
deprivation
RF for later menopause
being breastfed
higher cognitive ability
higher parity
Oocytes at:
20-28/40
birth
menarche
menopause
20-28/40- 5-6million
birth 2 million
menarche 400,000
menopause <1000
median duration of menopause
7 years, 5 is average
vasomotor symptoms
~75% women (70% western)
low E= narrow thermoneutral zone in hypothalamus
vaginal symptoms
~50% women
thin, reduced collagen to vaginal epithelium
high pH and low lactate
more infections
less secretions
CVD risk
Higher after menopause
may be reduced by 50% if HRT started within 10 years/>60yo
reduce atherosclerosis, CHD death
Osteoporosis
consider HRT if <60 and need treatment, especially if also having menopausal symptoms
reduced risk whilst taking which may persist but lessens after cessation
may be lower risk if taking longer
If higher peak in youth (ie 10% higher) 50% reduced risk later on
highest justbefore menopause
1 in 6 F - hip # (20% die in 1 month 30% 1 year, 50% lose independence)
Sleep changes
Reduced sleep will reduce cognition and memory
reduced by alcohol/medication use
Migraine
switch to less androgenic or micronised progestogen (or LNGIUD)
ccHRT
lowest dose of transdermal HRT (titrate slowly) as reduced fluctuations in levels
No increased stroke risk
peak of migraines is early 40s, worsened by E
Incontinence
urge incontinence precipitated by lower estradiol levels, worse if longer deficiency
give pv oestrogens- proliferation of urogenital tract
Assessment by age
> 45 history only (BMI and BP)
40-45 consider FSRH
<40 FSH x2 4-6 weeks apart
po oestrogens
do not check E2 levels
increased SHBG
prothrombotic first pass metabolism
increased risk stroke
-not noted in transdermal
menopause symptom questionnaires
Greene Climacteric Scale
Menopause Rating Scale
menopause-specific QoL
Testosterone availability
2/3 bound to SHBG
1/3 bound to albumin
~1% free
Free Androgen Index
110 x (total T / SHBG)
a guide to free testosterone
Other bloods to check in menopause care
FBC
Autoantibodies
T4/TSH
fasted glucose
catecholamine (phaeochromocytoma)
24hr urinary 5 hydroxyl.. acid (carcinoid syndrome)
Follow up after HRT
Every 3/12, 12/12 when settled
- effectiveness and side effects
-bleeding
-risk profile (with age/BMI)
-plan to stop or decrease
health promotion- breast/S/A/D/BMI
Lifestyle optimisation
BMI 18.5-24.9 (waist <76cm)
diet: increased protein, less red meatr, oily fish 2xweek, 25g fibre, mediterranean
150min exercise/week
Calcium and Vit D
<2 units/day
pelvic floor
screening
SPF
QRISK/JBS3
Lubricants
YES/SYLK
during intercourse or other times
Moisturisers
Replens/Regelle
Every 3 days, bioadhesive to vaginal walls
Ospemifene
SERM 60mg PO OD
reduce dryness and dyspareunia
Loss of desire
~40% women
Tibolone
Synthetic Steroid
estrogenic, progestogenic and androgenic properties
helps with- vasomotor, mood, libido
2.5mg PO OD
converted to active metabolites
increased bones mass- reduced vertebral but not hip #
Types of oestrogen
synthetic
natural
premarin
Synthetic
- Ethinylestradiol
-increased metabolic impact so not used in HRT
Natural
-estradiol, estrone and estriol
-soybeans/yams, closer to natural Es
Premarin
-conjugated oestrogen (50-65% estrone and equine)
How to choose progestogen
> 12/12 since LMP= continuous
OR - >5 years (protective effect of sequential lost), age 54 80% through
synthetic/plant derived
17 alpha hydroxyprogesterone derivatives
acetylated- MPA, megestrol A, cyproterone A
non-acetylated- dydrogesterone
19 nopregnone derivatives
acetylated- nomegesterol
nonacetylated- trimegestone
19- nortestosterone derivatives
ethylated:
estrones (NET/ethyndiol diacete)
gonanes (LNG/norgestel/DSG/norgestimate/gestodene)
non-ethylated
dienogest/DRSP
Bazedoxifene
SERM
Used with conjugated oestrogens
for progesterone intolerance
Oral HRT contains
predominantly oestrone- raised SHBG
Transdermal HRT contains
predominantly estradiol
- lower risk VTE/stroke/GB disease
-use if BMI >30
HRT implant- E
Estradiol
6 monthly
increased levels of estradiol so more likely for tachyphylaxis
how to manage subtotal hysterectomy
Give sequential HRT
If bleed- continue
If no bleed- continuous
how to manage ablation
combined continuous
?still endometrium present
how to manage endometriosis
give combined/tibolone for a few years
reduce risk of deposit growth
Initial doses
oral 1-2mg PO daily
patch 25-50mg 1 patch twice weekly
gel 1-2mg once daily (lenzetto start at 1 spray)
implant 25-50mg 6 monthly
conjugated 0.3-0.625mg
(bone sparing)
Cyclical progesterones
start on d1 cycle to reduce irregular bleeds
10-14/7 every 28/7
Long cycle progesterones
Every 3 months
-infrequent bleeds/side effects
-short term only
-increased risk of irreg bleeding
Oestrogenic side effects
breast tenderness (gamolenic acid/evening primrose)
bloating
nausea
cramps
headaches
dyspepsia (take po with food)
-try and persist 3/12
-reduce dose, change type/route
Progestogenic side effects
bloating
headache
acne
breast
mood
LAP/LBP
-change dose/type/route
-low cycle or 7/7 only
-LNGIUD/continuous low dose
-SERM
Mid life weight changes
Normal to gain 0.5kg/year
no evidence this increased with HRT, may change fat distribution
Stopping HRT
No reason to
makes sense to reduce and symptoms will reduce with time, consider at each review
Topical Oestrogens
Estradiol:
estring (7/5mcg ring for 3/12, max 2 year)
vagifem 910mcg OD 2/52, then twice weekly
cream 0.01% 1 applicator daily 1 month then twice weekly
Estriol:
Ovestin 0.1% daily until improvement then twice weekly
Blissel gel 50mcg daily for 3 weeks then twice weekly
Progesterone dosing
MPA 5mg OD or 10mg PO OD 14/7
Uterogestan 100mg OD or 200mg 14/7
can increased to 300 with higher doses
Testogel
1 sachet to clean inner thigh
should last 8 days
if nil improvement 6/12 or 5mg/d- stop
Testosterone in HRT
Taking HRT and low libido and low testosterone
off license, check level in 6-12/52
lack of evidence on long-term safety
potentially irreversible- voice, clitoromegaly, male pattern baldness
Neurokinin 3 receptor antagonist
Fezolinetant 45mg PO OD
For vasomotor symptoms- modulates activity at hypothalamic thermoregulatory centre
c/i in liver disease- now have to check LFTs before and during treatment
private px only
s/e- abdo pain, insomnia, diarrhea
Why micronised progesterones?
selective
reduced androgenic/mineralocorticoid/glucocorticoid activity
better safety profile
Cognition
increased risk dementia if HRT started >65 yo
do not give HRT just for dementia
increased risk if starting HRT early/POI
Colorectal Ca
?reduced risk if combined oral HRT- unclear mechanism
Breast Ca risk
small increase after 3 years
age 50-59 (over 5 years = extra 3 in 1000)
not seen if only E
85% with first degree relative with cancer
87% with cancer no first degree relativ
= risk recurrence if epithelial atypia/carcinoma in situ
most have no RF
Endometrial ca risk
small increase if combined sequentia; >5 years
reduced risk with ccHRT than no HRT
Vasomotor symptom control
Offer E as first line if nil c/i
Clonidine
SSRI/SNRI
Gaba
Clonidine
centrally acting alpha adrenoceptor agonist
flushing
50-75mcg BD
caution if on antihypertensives
ok with tamoxifen
s/e- dry mouth, sedation, nocturnal restlessness, dizziness, nausea
SSRI/SNRI
Venlafaxine(SNRI 37.5/75mg BD)/citalopram
fluoxetine no benefit
vasomotor only
s/e- GI, sexual, bone loss
avoid with tamoxifen- stops conversion to active metabolite so less effective
Estradiol levels
Check after 2/52 at least
normal- 200-300
>1000- reduce
Gabapentin
GABA analogue
900mg OD- reduces hot flushes by 50%
drowsy/dry mouth/dizzy
beta blockers
propranolol 80mg OD
anxiety/panic disorder/palpitations- good for autonomic symptoms not psychological
s/e- bradycardia, hypotension, GI, libido,
c/i in asthma
Psychological
Exercise- mood and sleep
Talking therapy- CBT, life coach, mindfulness
Phytooestrogens
isoflavones- legumes/red clover
lignans- flaxseed/bran
soy (increased in asian diet so reduced symptoms)
limited evidence, uncertain safety in breast Ca
Black Cohosh
?isoflavones effect by direct stimulation of E receptors
?evidence
c/i in liver disease, unsure in breast Ca
may help vasomotor
Bio identical meaning
same molecular structure as substance produced by the body
DHEA
levels reduce with age
?anti-ageing- skeleton/cognition/vagina/linbido
Osteoporosis diagnosis
T <-2.5
-1.0 to -2.5= osteopenia
C terminal peptide- marker of bone turnover
DXA/QUS
Osteoporosis prevention
Vit D, Calcium, Protein
BMI 19-25 with regular cycles (oestrogen protective)
30mins exercise most days
smoking, alcohol, steroids
>2 years HRT= reduced # risk
FRAX risk
low= sunlight, calcium in diet, exercise, smoking, alcohol
moderate= check BMD
high= treat without checking
Osteoporosis treatment
1000mg Calcium/day
400IU Vit D/day
-reduced vit d = low intestinal absorption of Calcium/phospate
Vit D normal range
Diet
- milk/dairy
-tinned salmon
-tofu
-brazil nutes
-boiled spinach
Sunlight- white person 20-30mins to forearms/face 2-3 times/week
normal= 70nmol/L
800-1000 units/day in diet
Bisphosphonates
alendronate- cheapest/1st line
take on empty stomach, upright 30mins after
oesophageal irritation not responsive to PPI
reduce osteoclast bone less- protective for 12 years
teratogenic
may increased ONJ/AF- holiday after 5 years to allow normal remodelling
Strontium
Vertebral/hip #, reduces bone resorption
s/e- diarhhoea, VTE, neuro symptoms, MI
r/v at 6-12/12 to assess CVD risk
Raloxifene
SERM
reduced vertebral # by 50% (estrogenic at bone receptors)
antioestrogenic at endometrium/breast receptors)
s/e- hot flush, cramps, arthralgia, lipids
Teriparitide
recombinant PTH
stimulates osteoblasts
peak at 6-9/12
Denosumab
bind to RANKL- reduce osteoclast function
s/e= immunosuppression
POI
<40 (>2 sds from mean) 1%
<30 0.1%
primary- chromosomal, genetic (Turner’s), fragile X, enzyme deficiency, AI disease
secondary- CT/RT, UAE, surgery, infection (TB/Mumps/malaria/VZV/SHigella)
TAH (even w/o oophorectomy)
85-90% idiopathic
17 alpha hydroxylase
HTN, hypokalemia, ovarian failure
HRT and Contraception POI
HRT until age 51 (better than CHC), nil increased Breast Ca risk
Contraception as 5-10% risk spontaneous
donor oocyte IVF- if spontaneous POI, IVF success rate is the same as normal population
Fibroids and HRT
shrink by up to 40% at menopause
HRT may increase volume
HMB in perimenopause- 90% amenorrheic with LNGIUD
can treat fibroids with UPA/GnRH whilst awaiting menopause
UPA- reduced volume by 50%
PCOS and HRT
chronic oestrogenic stimulation of endometrium
lack of ovulation- reduced progesterone secretion
increased risk hyperplasia, cancer, insulin/BMI
changes to cholesterol and androgens
- nil c/i to HRT but be aware of risk
Background CVD and HRT
may be beneficial if start HRT in 50s
not a c/i
HTN and HRT
may choose transdermal to reduce impact on RAAS
conjugated E can increase BP (will resolve if stopped)
cholesterol/lipids
may benefit from HRT
use statins
VTE risk with HRT
use micronised P (NET/MPA)
d/y haem if previous VTE- may anticoagulate before starting HRT
increased risk with raloxifene/high dose P
tibolone- increased stroke risk, unknown VTE risk
HRT and surgery
Do not stop transdermal
oral- small increased risk, no rationale for stopping, routine thromboprophlaxis
DM and HRT
Increased risk # and endometrial Ca
Thyroid problems and HRT
increased thyroxine can lead to raised SHBG/Testosterone/androgens
reduced clearance fo E2 and andorgens
increased conversion to estrone
oral E can increased TBG and reduce levothyroxine (may need to titrate dose)
Epilepsy
Enzyme inducer- transdermal HRT
may increased osteoporosis risk
BRCA carrier + oophorectomy
HRT until age 51
Previous Breast Ca
Can have vaginal E
c/i to systemic E
may be ok if receptor -ve/on tamoxifen (but 1/3 recurrence will be receptor positive)
discuss with breast team
Cancer rx and BMD
Tamoxifen increases
GnRH/aromatase decreases- DEXA
Amenorrheic with chemotherapy
increased risk based on age
>40 = >80%
30s 40-60%
<30 = 20%
unknown risk with monoclonal antibodies
Gynae Ca and HRT
Ovarian, Cervical, vaginal and vulval are not E dependent so can continue
avoid if endometrioid (or give combined)
Offer combined with cervical Ca if retained uterus
Endometrial Ca and HRT
limited evidence, nil known increased risk
Can theoretically offer combined after surgical rx
Melanoma/Colorectal Cancer and HRT
Melonoma may have some E receptors
consensus ok to given
HIV and HRT
Prefer transdermal as reduced GI s/e and VTE risk
BRCA
70% F breast Ca by age 80
<10% M with BRCA 2
BRCA 1 worse than 2
Ovarian Ca:
45% 1 20% 2
small increased risk prostate/pancreatic
Autosomal dominant
BRCA carrier surveillance
Annual breast MRI age 25 to 40
>40 MRI and mammography
Tamoxifen and topical oestrogen
Avoid
use acidic vaginal lbricants
BRCA, mastectomy and BSO
LNGIUD and transdermal HRT until normal age of menopause
Physiology of Menopause
-reduced sensitivity of ovary to LH/FSH (fewer binding sites as fewer follicles)
-increased anovulatory cycles
no Progesterone to stabilise endometrium-> E related breakthrough bleeding
-increased LH and FSH as no -ve feedback (reduced inhibin on FSH = much more raised than LH)
Symptoms of POI
oligo/amenorrhoea >4 months
40-50% vaginal atrophy
FSH >30/40 4-6 weeks apart
12-14% asymptomatic
Treatments of POI
HRT>COCP until ~51
Calcium, Vit D and exercise to protect bones
DEXA if indicated
reduced risk Breast Ca
Bleeding on HRT
1) examination, swabs, smear
2) If >6 months since started or >3 months since dose change
= TVS within 6 weeks
sHRT >7mm
cHRT >4mm
=pipelle/hysteroscopy
Endometrial assessment of HRT (Risk factors)
1 major or 3 minor= endometrial assessment
Major:
BMI >40
Lynch/Cowden
Nil Progesterone and uterus
Minor:
BMI >30
PCOS
DM
Change to bleeding on HRT- likelihood benign
50-60% normal
</= 30% polyp
Change to bleeding on HRT- likelihood sinister
PMB (nil rx)
11% hyperplasia
9% Ca
sHRT
2.5-16% hyperplasia
5% Ca
ccHRT
1-2% hyperplasia
1-2% Ca
When to do urgent TVS
> 7 day withdrawal bleed
very heavy bleed
4 weeks of light bleeding
2 minor risk factors
bleeding on cc after amenorrhoea
unscheduled bleeding on sHRT after light, regular cycles
How to manage HRT when bleeding
Can continue but ensure to write on histology form
if declines USS, wean off HRT
No bleeding- when to do pipelle
ET >10mm
Tailoring HRT when bleeding
reduced doses increase menorrhoea rates
Increase medroxyprogesterone to 200mg, or give pv (off licence)
oral>transdermal
> 4 years into LNGIUD- ?exchange
POI risks
lower risk of Breast Ca, E replacement does not increase this risk if <50 yo
VTE- uncertain, use transdermal if high BMI
POI route/dose
Nil consensus
Recommend 75-100mcg or 2mg gel/patch
aim to achieve physiological E2 levels (300-500)
Benefits of HRT
Improvement in vasomotor instability symptoms
Improvement in mood
Improvement of vaginal dryness
Improvement of urinary symptoms
Improved BMD / Reduction of osteoporosis risk
Reduction in cardiovascular disease
Reduction colorectal cancer risk
