1
Q
what are guidelines we follow for menopause
A
SOGC
Canadian Menopause Society
2
Q
what is the average age of menopause
A
51
3
Q
what is the age range for menopause
A
45-55
women spend 1/3 of their lives in a post-menopause state
4
Q
what happened to life expectancy for menopausal women throughout the years
A
has gone up
5
Q
what are the stages of menopause
A
pre menopause
perimenopause
menopause
post menopause
6
Q
what age range is pre menopause and what are the estrogen levels
A
reproductive years, aka before 35 at least
estrogen is high
no symptoms
7
Q
what age range is peri menopause and what are the estrogen levels
A
35/45-51
estrogen starts fluctuating but trending down
symptoms are severe!!
8
Q
what age range is menopause and what are the estrogen levels
A
51
estrogen is low
symptoms start dying down
9
Q
what age range is postmenopause and what are the estrogen levels
A
51+
symptoms died down
10
Q
what does menopause mean
A
meno - menstruation
pause - stop
11
Q
what is the definition of menopause
A
diagnosed by 1 year without a period due to natural causes (not induced)
after this one year of no period, then it is called post-menopause
12
Q
what is induced menopause
A
menopause following surgical remove of ovaries or ablation of ovaries through chemo or radiation
13
Q
what is early menopause
A
before 45 yo
14
Q
what is premature menopause
A
before 40 yo
premature ovarian insufficiency
15
Q
in MENOPAUSE what happens to the hormones
A
estrogen and progesterone are low
this means the negative feedback loop is gone, and FSH and LH remain high
16
Q
females are born with a finite number of…?
A
oocytes (eggs)
17
Q
what are eggs lost to?
A
ovulation
and atresia (dying off)
18
Q
how many eggs are left by menopause
A
300-400 (most are not effective anymore)
19
Q
does ovulation still occur during perimenopause
A
yes, but will be more erratic
20
Q
do COC cause menopause
A
no
MENOPAUSE HAPPENS NATURALLY
21
Q
do COC help with fertility
A
no
follicles will be lost no matter what, due to atresia
22
Q
what happens to the ovaries during menopause
A
decreased number of follicles
reduced response to FSH and LH
23
Q
what happens to the menstrual cycle during menopause transition
A
anovulatory cycles occur, making menstruation irregular
aka no egg gets released
24
Q
what is a metabolite of both estrone and estradiol
A
estriol
25
where does estrone come from
androstenedione
26
where does estradiol come from
testosterone
27
what is the most potent estrogen
estradiol
28
what is the least potent estrogen
estriol
29
what is the main endogenous hormone
estradiol
30
where is estradiol produced
ovaries
31
where is estriol produced
It is a metabolite of estradiol and estrone
highest levels are during pregnancy bc it is produce by the placenta
32
where is estrone produced
liver
33
estradiol can also be converted from?
estrone
34
after menopause, how does estradiol get produced (since now the ovaries aren't making estrogen that much)?
estrone is still produced by liver, and then estrone converts into estradiol
as opposed to the ovaries directly making estradiol, like in premenopause
35
what happens to testosterone levels in menopause
stay pretty much the same as before, but start to gradually decline
unlike estrogen which falls pretty fast
36
what are benefits of having estrogen in the body
breast milk production
controls cholesterol in liver and heart
prepares uterus for fetus
preserves bone strength
37
what are harmful effects of estrogen
increases breast and uterus cancer risk
38
what happens to estrogen and progesterone during PERIMENOPAUSE
higher and fluctuating estrogen levels
lower progesterone levels
39
what happens to estrogen and progesterone during POSTMENOPAUSE
low E + P
sustained high FSH and LH levels
40
should you do hormone tests during the menopause phase
NO
they are always fluctuating
41
how is testosterone made
25% from ovaries
25% adrenal
50% peripheral conversion from its precursor androstenedione
42
what are benefits of testosterone
maintains libido
general well-being
43
why does testosterone gradually decline, whereas estrogen drops fast
testosterone declines bc of aging
estrogen drops fast because of menopause
44
how much does testosterone drop by if menopause is induced
50%
45
what is the only androgen that gets produced by the adrenal gland, that isnt produced by ovaries
DHEA-S
46
what will DHEA-S lab work tell you
if testosterone insufficiency is coming from the adrenal glands or the ovaries
*if it's low, that means the adrenal glands aren't making enough testosterone
47
how is menopause diagnosed
cessation of period for 12 months
high FSH levels (>30)
48
how is perimenopause diagnosed
+/- symptoms!!!
+/- menstrual cycle changes
HAVE TO LOOK AT BOTH, bc a pt might have one or the other and either/or can both be used to diagnose
49
what should NOT be used to diagnose perimenopause
FSH levels
remember, at this time, it's fluctuating a lot
50
what are the symptoms of perimenopause
vasomotor symptoms (VMS)
--> night sweats, hot flashes
mood sx --> irritability, PMS, depression
hard to concentrate, brain fog
GSM --> vaginal dryness, dyspareunia frequent UTIs
insomnia, muscle pain, breast tenderness, headaches, heart palpitations, low libido, dry skin, hair changes
51
how long can VMS sx last
7-8 years (~4.5 years after menopause)
can even be longer than 10 years
52
is pregnancy still possible during perimenopause
yes
because you are still technically having a period, therefore can still ovulate
53
why are severe hot flashes that occur earlier in perimenopause bad?
can lead to negative CV outcomes later in life
- like a heart attack
negative effects on brain health
54
during early perimenopause, what happens to their period
comes more frequent
heavier/lighter/shorter/longer
55
during late perimenopause, what happens to their period
comes farther apart, might miss some
heavier/lighter/shorter/longer
56
should estrogen levels be used to determine severity of a hot flash/night sweat
no
57
why do VSM sx happen
KNDy neurons in the hypothalamus are in abundance when estrogen levels are low
these neurons are control thermoregulatory centres in the hypothalamus
58
what drug can be used off label to tx VSM sx
SSRIs
59
which agents are indicated for VSM sx because they inhibit KNDy neurons
fezolinetant - NK3R antagonist
elizenatant - NK1, 3R antagoist
60
what does GSM sx mean
genito-urinary syndrome of menopause
61
why do GSM sx occur
degeneration of connective tissue:
- collagen, elastin, smooth muscle
reduced vaginal blood flow and secretions because of thinner mucosa
vaginal shortening and narrowing
glycogen decreases
62
how is glycogen decreasing related to vaginal pH
glycogen is a substrate for lactobacilli, which make lactic acid in the vagina
when glycogen decreases, so does lactic acid, pH shifts from acidic to basic (pH goes up)
63
what are GSM sx examples
vaginal dryness
irritation/itching
painful intercourse
spotting after intercourse
recurrent UTIs
LUTs
low libido
64
which sx will get better after menopause
VSM
65
which sx will get WORSE after menopause
GSM
66
people who experience premature menopause should start estrogen therapy because...?
increased CV risk if they don't
estrogen is a protective barrier that reduces plaque buildup in arteries and prevents atherosclerosis
67
what happens to bone health during menopause
bone loss at a faster rate bc less estrogen
68
what are the effects of early/premature menopause
osteoporosis
CVD
cognitive impairment
early mortality
69
MENOPAUSE LECTURE 2
70
what are non-pharm options to tx menopause sx
cooling techniques
- dressing in layers, breathable fabrics, using a. fan, avoiding riggers, excessive alcohol, spicy foods
maintain healthy weight
stop smoking
exercise
yoga
71
what are complementary therapies for menopause sx
CBT
mindfulness
72
what is progestogen
both natural and synthetic progesterone
progesterone - natural
progestin - synthetic (like in CHC)
73
what are the benefits of MHT
sx improvement - VMS, sleep, mood, QofL, GSM (using vaginal estrogen tx)
prevention of osteoporosis
74
what are the risks of MHT
CVD - CHD, stroke, VTE
breast cancer
75
is MHT safe for most women?
yes
76
when should MHT be started?
women less than 60yo
OR
less than 10 years since their last menstrual period + experiencing sx
77
when should MHT be used for women who have early/premature menopause
up until the average age of menopause (51y)
eg. if they got menopause at 39, MHT should be continued until 51 (avg age)
78
which hormones are involved in MHT
systemic estrogen
- for VMS and sx
progestogen
- for endometrial protection, while using systemic estrogen
vaginal estrogen therapy
- GSM
79
do all women get the same MHT tx?
no
tx should be individualized to:
- sx
- Med conditions
- risk factors
- pt preferences
80
contraindications to MHT
estrogen:
- AUB
- hx/active breast cancer
- coronary heart disease
- hx/active VTE
- hx/active stroke
- thrombophilia
- active liver disease
- pregnancy
progestogen:
- AUB
- hx/active breast cancer
81
what is the Women's Health Initiative (WHI)
RCT to assess if MHT reduced CV morbidity and mortality
82
what were the two arms of the WHI
1. estrogen+progestin
2. estrogen only
83
which arm of the WHI stopped earlier
estrogen+progestin arm
84
what types of estrogen and progesterone were used in the WHI
conjugated estrogen
medroxyprogesterone
85
what were the absolute results of the E+P arm of the WHI
showed a minor increase in CHD, stroke, VTE, breast cancer
showed significant benefit in reducing colorectal cancer and hip fractures
86
why did the results of the E+P arm scare women
because the data displayed showed the RELATIVE risk of the harmful stuff, not the ABSOLUTE risk which was muchhhh lower
eg. relative risk of VTE was 113%, but absolute risk was actually just 18%
87
when looking at confidence intervals, which is the more important value to be looking at
adjusted confidence interval
and if it crosses 1, it is not statistically significant
88
what were the risk results of the estrogen only arm of the WHI
stroke
*still low*
89
what were the benefit results of the estrogen only arm of the WHI
reduced hip fractures
90
what kind of women participated in the WHI
mean age 63
women without menopausal sx
91
why should estrogen NOT be initiated AFTER menopause
it will start to have the opposite effect on CV health and will actually start to create plaque ruptures and possible MI
92
what is the timing hypothesis of starting MHT
if started early (less than 10 years after last period), estrogen preserves arteries and CV health
if started too late (after 60y), estrogen has opposite effect and increases CV risk
93
greatest risk of VTE with MHT is when?
within first year of using it
94
what route of estrogen therapy has a lower VTE risk
transdermal
*based on observational studies*
95
is transdermal MHT the same as transdermal CHC
NO
the estrogen in MHT is 4-5x less potent than CHC
96
individuals with comorbidites like HTN, smoking, obesity, diabetes should consider what type of MHT
transdermal estrogen
low dose estrogen
97
is family history of CVD events a c/I to MHT
NO!
only personal hx is a c/i
98
breast cancer was a risk in which arm of the WHI
estrogen + progestogen for more than 5 years using
99
which type of progestogen is linked to a lower risk in breast cancer
micronized progesterone
aka natural is better than synthetic
100
is family hx of breast cancer a c/I to MHT?
NO!
BUT, if pt has 2+ first degree relatives with hx of breast cancer, be very cautious, bc chances are the pt might get it as well
101
what are breast cancer risk factors that can be reduced with lifestyle?
alcohol >2 drinks/day
post-menopause obesity
1st child at age >30y
102
what are non-modifiable risk factors for breast cancer
early menarche
late menopause
strong family hx
high breast density
103
what were the WHI E+P arm results on cognition
no improvement with E+P
104
MENOPAUSE LECTURE 3
105
if a pt had a hysterectomy, do they need E+P?
only estrogen
106
what can be given to pts >60y, OR >10 years since menopause OR have c/I to MHT and high risk of CVD
non-hormonal rx options
107
what are the systemic MHT regimens for POSTMENOPAUSE
E+P continuous
E+P cyclic
E alone (hysterectomy)
108
is cyclic better than continuous?
no
continuous is actually easier to adhere to, and works the same, so most women will follow that regimen
109
what does cyclic E+P look like
estrogen continuous
but progestogen for the first 12-14 days of each month
this leads to a withdrawal bleed for the last 14 days of the month
indicated for: final menstrual period less than a year ago
110
what is the therapy for PERIMENOPAUSE
E+P cyclic
progesterone alone
low dose CHC or
estrogen + LNG-IUS
111
when should you consider CHC or estrogen+LNG-IUS for perimenopause
if irregular bleeding occurs
pt still wants contraceptive benefits
112
which estrogens are found in the human body
estradiol
estriol
estrone
113
which types of estrogens are used in MHT
conjugated estrogen
17B-estradiol
estrone
114
what formulations of MHT are available for estrogens
oral
transdermal patch or gel
vaginal creams, tablets, ovules
- for GSM
115
which types of progestogens are used in MHT
micronized progesterone aka Prometrium
synthetic progestins like:
medroxyprogesterone
norethindrone acetate
levonorgestrel
drospirenone
116
what formulations do progestogens for MHT come in
oral
transdermal patch (in combo with estrogen tho)
LNG-IUS (not approved by HC to be used with estrogen for menopause)
117
what is the equivalence of all the types of estrogen based on formulations
0.625mg CE = 1mg 17ß-estradiol (oral) = 5μg ethinyl estradiol =
50μg patch = 1 - 2 pumps Estrogel = 1 mg Divigel
118
what are the systemic routes of admin for estrogen
oral
transdermal
119
what are benefits of oral estrogen over transdermal
improve lipids by increasing HDL and decreasing LDL
120
what are risks of using oral estrogen
high first pass effect
increase TG
increase SHBG
increase thyroid binding globulin
increase CRP
fluctuations in hormones --> can lead to bad migraines
121
what are benefits of transdermal estrogen
no first pass effect
less hormone fluctuations
122
when to choose transdermal over oral estrogen
to avoid first pass in pts with:
- smoking
- high TGs
- HTN
- low libido
- gall bladder disease
- risk factors for VTE/CVD
for pts wanting consistent levels:
- pts with migraines
- shift workers
- pts with malabsorption issues
123
what are the transdermal estrogen products on the market
patches - estradot, climara
gel: Estrogel, divigel
124
what is the difference between estradot and climara
estradot - twice a week application + comes with more dose options
climara - once a week
125
what is the difference between Estrogel and divigel
estrogel - applied daily to the same area
divigel - applied daily to any area + more dose options
126
which types of estrogen are found in oral products
conjugated estrogen
or
17B-estradiol
127
which type of estrogen is in transdermals
17B-estradiol
128
when starting a pt on systemic estrogen (oral or transdermal), what is the dosing like
low to standard
0.5mg-1mg of oral 17B-estradiol
129
what is the starting dose of progestogen for systemic MHT - continuous
MPA - 2.5mg
micronized - 100mg daily
130
what is the starting dose of progestogen for systemic MHT - cyclic
MPA 5mg
micronized - 200mg for 12-14 days
131
what is the most common a/e of MHT
breakthrough bleeding
132
what are systemic estrogen related a/e of MHT
breast tenderness
fluid retention
headaches
nausea
133
what are vaginal estrogen related a/e
vaginal discharge
irritation
134
what are progestogen related a/e of MHT
breast tenderness
fluid retention
bloating
headaches
depression
PMS
fatigue
135
what s/e is specific to micronized progesterone
sleepiness
nightmares
136
when will a/e of MHT improve
within 2-4 weeks
137
how long will BTB occur
6-9 months after starting continuous E+P
138
when should a pt be referred in regards to BTB
if its been more than 12 months of BTB
139
what is tibolone (Tibella)
selective tissue estrogenic activity regulator (STEAR)
synthetic steroid, which converts into 3 metabolites that have: estrogenic, progestognenic and androgenic activity
140
dose of tibolone for MHT
2.5mg oral tablet daily
141
a/e of tibolone
fatigue
breast tenderness
fluid retention
stomach upset
nausea
increased appetite
142
what is an advantage of tibolone over E+P therapy?
less BTB
143
what are tissue-selective estrogen complexes (TSEC's)
estrogen + selective estrogen receptor modulator (SERM)
144
what is an example of a SERM that can be combined with a conjugated estrogen
bazedoxifene
145
what does bazedoxifene do
antagonist of estrogen receptors in the uterus and breast
agonist effects on bones
146
what is an example of a TSEC
Duavive - 0.45mg CE + 20mg bazedoxifene
147
why might a TSEC be preferred to E+P therapy
less BTB and less breast tenderness
148
what do progestogens tx in menopasue
VMS sx at higher doses
endometrial protection with estrogen
used if woman has c/I to estrogen
149
what are bioidentical hormones
chemically identical in molecular structure to a human hormone
150
what are examples of bioidentical hormones
estradiol
estrone
estriol
progesterone
testosterone
DHEA
151
what is the precursor to bioidentical estrogen hormones
soy
152
what is the precursor to bioidentical progesterone hormones
mexican yam
153
are compounded bioidentical hormones the same as "natural" hormones
no
not in the sense that the BH are naturally made or occurring
154
compounded estrogen products use which form of estrogen in combo with other estrogens
estriol
155
is compounded BHT safer than commercially available MHT
no
156
what is the potency of estriol
1/80 of estradiol
157
compounded progesterone creams should NOT be combined with...?
estrogen
158
MHT dosing is adjusted based on what?
symptoms
bc hormones are fluctuating in perimenopausal women, so they wouldn't be accurate measurements
159
when should MHT indicated be reassessed
every year or at regular intervals
160
when should MHT be d/c
no age limit
can keep going, even into 60s
it's an individual decision
161
what is the algorithm for treating VMS sx if last period was less than a year ago?
see slide 32
1. discuss increasing calcium + VitD
2. need for contraception?
yes --> low dose CHC or LNG-IUS + estrogen or MHT + condoms
yes (but c/I to estrogen) --> non hormonal rx options + POP OR IUDs
no --> E+P or TSEC or tibolone or non hormonal rx
no (but c/I to estrogen or >60 or >10 yrs since period or high CV risk) --> non hormonal rx
162
what is the algorithm for treating VMS sx if last period was more than a year ago?
see slide 32
1.VitD + calcium
2. nonpharm measures
3.
no c/I --> E+P or TSEC or tibolone or non hormonal rx
c/I to estrogen or >60 or >10 yrs since period or high CV risk) --> non hormonal rx
hysterectomy --> estrogen only or non hormonal therapy
163
what are non-hormonal options for VMS
gabapentin
antidepressants
clonidine
oxybutinin
164
what are non-hormonal options for GSM
oxybutinin (for overactive bladder)
165
what are non-hormonal options for sleep
gabapentin (sedating at high doses)
antidpressants
166
what are non-hormonal options for mood
gabapentin
antidepressants
167
transdermal estrogen is preferred when pt has..?
comorbidities
DM, HTN, high TG, elevated CV risk, VTE risk, smoking, obesity, migraines, malabsorption, gallstones
168
which non-hormonal option are NK receptor antagonist
fezolinetant (Veozah)
elinzanetant (Lynkuet)
169
what does fezolinetant do
targets KNDy neurons by blocking NK B from binding to the NK3 receptor on KNDy neuron
170
what does fezolinetant tx
VMS
improvement seen after 1 week
171
s/e of fezolinetant
headache
ab pain
nausea
liver injury - greatest risk within first 40 days
- rare
172
c/I to fezolinetant
if baseline ALT >2x normal
cirrhosis
CrCl <30
173
d/I with fezolinetant
CYP1A2 inhibitors
174
what should be monitored while on fezolinetant
baseline liver and bilirubin
- repeat every month for 3 months, then q3months after
175
when should fezolinetant be discontinued
if liver values are >5x normal
176
how does elinzanetant work
antagonist of both NK3 and NK1 receptors on KNDy neurons
177
s/e of elinzanetant
headache
ab pain
fatigue
GERD
somnolence (sleepy)
dizziness
178
is hepatic monitoring required with elinzanetant
NO
179
c/I to elinzanetant
strong CYP3A4 inhibitors
- if it's a moderate inhibitor, reduce dose of elinzanetant by half
CrCl <30
liver impairment
180
compare gabapentin, oxybutinin, clonidine, SSRIs to NK antagonists
NK ants are better at treating VMS
NK ants work faster at tx sx
181
what are non-hormonal OTC options for GSM
lubricants
moisturizers
182
what are hormonal therapies for GSM
vaginal estrogen
intravaginal DHEA
ospemifene
systemic estrogen
183
what are non-pharm options for GSM
regular sexual activity
dilators
pelvic floor therapy
laser
184
what are water based lubricants
feel more natural
shorter acting
185
what are silicone based lubricants
sticky
long lasting
186
what are oil based lubricants
natural based oils like olive/coconut
avoid with condoms
187
which non-hormonals have been shown to be as effective as vaginal estrogen
polycarbophil
hyaluronic acid
188
is progesterone needed for endometrial protection
no
estrogen is enough
189
what does vaginal estrogen prevent
recurrent UTIs
190
can vaginal products be used in combo with MHT
yes
191
what are examples of vaginal estrogen products
intravaginal cream
- CE (Premarin)
- estrone (Estragyn)
ring
- intravaginal sustained release
- change every 3 months
- Estring
tablets
- estradiol (Vagifem, Imvexxy)
192
what are new products for GSM
intravaginal DHEA
- prasterone aka Intrarosa
- inactive estrogen and androgen precursor
oral SERM
- ospemifene (Osphena)
193
s/e of prasterone
vaginal discharge
194
s/e of ospemifene
hot flashes
