Post-Menopausal Hormone Replacement Therapy
1) 52 y/o
post-menopausal female presents with hot flashes. They have gotten to the point of
interrupting her sleep. She a=
lso
has them several times a day. She has no significant personal or family medi=
cal history.
She takes no medications. She=
has
never had a hysterectomy. She wants something to “fix” her. What is her best option?
Estrogens markedly improve the frequency and severity = of vasomotor symptoms. The benefit is dose-related but even lower doses of estrogen are often effective. Generally estrogen replacement red= uces the frequency by 80-100%.
2) She wants =
to know
how soon she will notice a difference as she is miserable.
Relief is usually substantial within 4 weeks after sta=
rting
the standard dose of estrogen (1mg estradiol or .625 conjugated estrogen).<=
span
style=3D'mso-spacerun:yes'> Lower doses may not have maximal e=
ffects
for 8-12 weeks but are associated with lower rates of side effects (e.g. br=
east
tenderness, uterine bleeding).
3) She has he=
ard “stories”
about hormone replacement and wants to know what other treatments are avail=
able
and how effective they are in reducing her symptoms. What will you tell her?
&nbs= p; Estrogen &= nbsp; &nbs= p; 0.625 mg/d &n= bsp; 80-= 100% reduction in hot flashes
&nbs= p; Megestrol &= nbsp; 20 mg bid &= nbsp; &nbs= p; 50% reduction in hot flashes
&nbs= p; Venlafexine (SSRI) 75 mg/d &nb= sp; = 35% reduction in hot flashes
&nbs= p; Gabapentin &= nbsp; 300 mg/tid &= nbsp; &nbs= p; 30% reduction in hot flashes
&nbs= p; Clonidine &= nbsp; &nbs= p; 0.1 mg transdermal = ; 25% reduction in hot flashes
Citalopram, Sertraline, nor Methyldopa show benefit ov= er placebo.
4) Given that=
other options
are not as effective, she thinks she wants to start hormonal therapy. What =
short
term risks associated with HRT should you discuss with her (and document) so
that she can make an informed decision?
1) Thromboembolic event= s: 2-3 fold increase in risk
2) = CHD: &= nbsp; -Strong evidence from 2 RCT’s suggest increased risk CHD in first year (relat= ive harm 1.5).
&= nbsp; -World Health Initiative RCT (WHI) suggests persistent CHD risk (with absolute risk increasing with age)
CHD events caused per 10,000 women in 1 year &= nbsp; (CHD Absolute Risk)
|
|
Aged 55-64 yrs |
Aged 65-74 yrs |
Aged 75-84 yrs |
|
CHD events WHI |
6 |
9 |
12 |
3)St= roke: &= nbsp; -WHI suggests increased risk of stroke (with absolute risk increasing with age)<= /p>
Strokes caused per 10,000 women in 1 year (Stroke Absolute risk)
|
|
Aged 55-64 yrs |
Aged 65-74 yrs |
Aged 75-84 yrs |
|
Stroke events WHI |
4 |
9 |
19 |
&nbs= p; 4)Cholecystitis:= -Increased risk of gall bladder disease by about 40%
5) What are t=
he long
term risks associated with HRT should you discuss (and document) with her?
Breast Cancer:&= nbsp;
· Short term (< 5yrs) Estrogen use does not confer increased risk of breast cancer = ;
· Long term (>5 yrs) Estrogen use is associ= ated with increased risk of breast cancer (with absolute risk increasing with lo= nger duration of use and older age)
Invasive Breast Cancer cases caused per 10,000 women p= er yr (Absolute Risk)
|
|
Aged 55-64 yrs |
Aged 65-74 yrs |
Aged 75-84 yrs |
|
Breast cancer cases (>5 yrs use) Meta- Analys=
is |
7-11 |
10-15 |
11-17 |
|
Breast cancer cases (> 5yrs use) WHI |
8 |
11 |
12 |
Overall, the rate of adverse events with estrogen plus progestin is hi= gher than that with estrogen alone.
6) What do you
recommend?
· Advise the patient that there is a small but real risk for thromboembolic, CHD and stroke events.
· Advise her that HRT remains the single best option for treating “hot flashes”
· Because she still has an intact uterus, she should take progestin in addition to estrogen to decrease the risk of uteri= ne hyperplasia and cancer.
· Use the lowest dose that adequately controls symptoms.
7) How long s=
hould
you tell her she will need to continue HRT? What do you do about recurrent =
hot
flashes off HRT? Is there a
“best” way to discontinue HRT?
The duration is difficult to determine. It is reasonable to try discontinu= ing HRT every 6-12 months. If symptoms recur, restarting and then gradually tapering the dose or the number of days per week that hormones are used may= be helpful. Infrequently, vasomo= tor symptoms persist and require long term treatment. The data is as follows:
~ 50% of women will have no difficulty stopping HRT
~ 40% will have vasomotor symptoms that are mild and r= esolve over a few months
~ 10% will have recurrent symptoms that are severe and persistent
“Dose taper”
· Progressive taper over several months. ( Ex: 0.0625mg/d x 1 month, then 0.4 mg/d x 1 month, then 0.3 mg/d x 1 month, then stop)
“Day taper”
· Slowly decrease the number of days/week of H= RT use (Ex: 0.625 mg on Mon-Friday. Once tolerated for a month, decrease to 0.= 625 mg/d on Tuesday- Friday, etc)
8) The patien=
t stays
on HRT for several years and is finally able to tolerate now only mild hot
flashes without any medications. However,
she is complaining of vaginal itching and discomfort with intercourse. What are her options at this point=
?
Unlike hot flashes, vaginal symptoms generally persist= or worsen with aging. These symptoms can include dryness, discomfort, itching,= and dyspareunia.
Vaginal estrogens are highly effective with improvemen= t or relief reported by 80-100% of treated women. They are preferred over systemic estrogen for localized symptoms.
Her options include vaginal creams (premarin or estrac= e), vaginal tablet (vagifem), or vaginal ring (estring). Replens which is a vaginal moistur= izer has been found to be as effective as estrogen vaginal cream for the treatme= nt of vaginal symptoms.
9) Does she h=
ave to
take progestin with the vaginal estrogens since she still has a uterus?
No, at the recommended dose and frequency, the additio= n of progestin is not necessary to protect the uterus.
10) Are there=
any
formal guidelines for post-menopausal hormone therapy?
Yes, ACOG and FDA recommend HRT be used at the lowest =
dose
for the shortest possible time for the treatment of menopausal symptoms.