MENOPAUSE – NOVEMBER 7TH , 2002



MENOPAUSE – NOVEMBER 7TH , 2002

Note: Brown said there will likely be short answer questions on the final

Vaginal products available for HRT

-these are used to treat symptoms of urogenital aging which include

-vaginal dryness **

-pain on intercourse (dyspurunia)** ** main ones

-incontinence – minor relationship

-infections (increased chance of occurring)

-used when patient complains of vaginal symptoms

1. Estring

-it is a ring with core of estrogen

-inserted up into vagina and stays in for 3 months

-releases local amount of estrogen ( does not get absorbed into body

-local therapy only

-every 3 months it needs to be released

-imp to tell patients to actually remove the Estring before inserting another one

-usually does not fall out but if it does can put back in

-should not interfere with intercourse, but if needed can take out and put back in

2. VagiFem

-tablet that comes with an applicator

-inserted daily x 2weeks and then 2x weekly

-only provides local estrogen ( not absorbed into body

3. Premarin vag cream

-cream comes with applicator

-many doses used

-common dose used is 1g = 0.625 of CEE (Premarin)

-can insert as needed – no right dose for it (i.e. can use 1x/week, everyday, etc)

-the estrogen from this product can get absorbed

Progestin use in menopause

Why do you need to use Progestin in menopause?

-to prevent endometrial proliferation

Progestin products available

1. Provera

-contains MPA

2. Prometrium

-contains progesterone (P4)

3. Combination products

-contain norethindrone acetate (NETA) – called norcistrone in Europe

-don’t worry about doses because are fixed

a. Estracomb

-large patch

-package contains 4 single patches (of plain estrogen) and 4 double patches (made up of 2 smaller patches attached together containing both estrogen and progesterone)

-should wear single patches 1st for 2 weeks and then the double patches x 2 weeks

-the patches are changed 2x/week so this should one package should last for 4 weeks

-50 mcg patch with progesterone in it

-this is a cyclic regimen so if want a cyclic regimen and a transdermal product use this!

-can also use alternating patches

-for example one single followed by one double patch every week x 4 weeks

-works as continuous therapy

-therefore may or may not bleed while on this product

b. Estalis

-combination patch wit Estrogen (E) and Progesterone (P) in each patch

-this is a continuous regimen

-new product

c. FemHRT

-pill with E and P in it

-estrogen dose = 5 mcg (EE) = 0.625 mg of CEE

When should these products (a, b or c) be used?

-for compliance and when patients don’t want to take an Estraderm patch and separate pill of progestin

-simple way of taking both in one

Indications for progestin products

Provera (MPA) vs. Prometrium (P4)

-Study:

-used estrogen alone ( ( HDL

-if combine Prometrium and estrogen ( ( HDL (equivalent to above)

-if combine Provera and estrogen ( HDL only increased a little bit

-so if someone has low HDL would put them on an oral estrogen product (last week) and Prometrium

-low HDL in women < 1.2 mmol/L

-Prometrium is contained in peanut oil so if allergy should not be using this

-Prometrium also causes sedation

-progesterone itself has anesthetic properties at very high doses

-sleep studies with Prometrium show that it will enhance sleep and give pt good quality sleep

-so if patient does not sleep well, give them Prometrium

-effects will occur immediately

-if effect of sleep is too much for patient they should insert the pill vaginally as it will not cause sedation (use same dose/pill and insert in vagina)

In summary, use Prometrium when patient has:

-low HDL

-no allergy to peanuts

-difficulty sleeping

How do Provera, Prometrium, and NETA affect the endometrium?

-Provera changes the lining into a secretary uterus ( protection

-prometrium has profound antimitotic effect (at low doses)

-causes down regulation of estrogen receptors on the surface of the endometrium

-so there is no proliferation of the endometrium

-so when given, may not have a secretory change and may not get any bleeding

-dose dependent effect – i.e. at high doses it will cause secretary change

-protects endometrium from over proliferation

-at doses < 200 mg ( antimitotic

-at doses > 300 mg ( secretary changes

-norethindrone

-acts like Provera

-same effect on HDL cholesterol

-so if have low HDL cholesterol may not also want to have her on a combination product

Dosing Regimens

Dosing of Progestin

1. Cyclic regimen

-given for X days during the month

-usually given for days 12-14 of cycle every month

a. Provera ( 5 mg x 12 days

-may have seen as 10mg x 10 days

-evidence is showing that in progestin therapy length of days are more important then dose

-so ok to cut down dose to 5mg and extent period of time that it is given for

-if don’t get period are not getting enough stimulation of endometrium to allow for secretary changes

b. Prometrium ( 200 mg for 12 or 14 days of each month

-if taken in cyclic regimen need to monitor when getting period

-patient may not get period

-study showed that when used at 200mg dose 50% of patients by 6 months of therapy they had amenorrhea

-it is ok to either not have a period or to have it after day 10

-counsel patients that may or may not bleed after day 10 and this is normal

2. Continuous

-given everyday

a. Provera ( 2.5 mg daily

b. Prometrium ( 100 mg qhs

-tell patients that may have unpredictable spotting or bleeding for 1st 6-8 months

-if problem to patient change to cyclic therapy

-can also use 200mg of prometrium for the 1st year if want to absolutely avoid bleeding

Dosing of Estrogen

-can give days 1-21 but there is no rationale for using this

-when stop Estrogen, symptoms may come back

-so does not really make sense why do this… should use it continuously

To explain to patients…

-estrogen is like the fertilizer on lawn, making lining/endometrium grow

-progesterone is like lawnmower

-so if allow endometrium to build and then change to secretary lining with progestin will get a regular period and know when it will come

-so bleeding here should occur after the 10th day of progestin therapy

-i.e. if taking progestin day 1to12 of every month, she should not have bleeding before 10th day

-if bleeding occurs before 10th day, it is abnormal and needs to be investigated because may have mixed endometrium (i.e. not fully secretary) ( do ultrasound to check for hyperplasia

-if bleeding after 10th day of progestin therapy means that entire lining has become secretary and endometrium is healthy

-this may be confusing because patient may get bleeding while still taking the progesterone (i.e. on day 10 instead of at end of progestin therapy on day 12)

-when taking progestin continuously = cutting grass every night

-so in 1st 6-8 months may have unpredictable spotting or bleeding

-but if there is spotting or bleeding after 1 year it is abnormal ( ultrasound or biopsy

-given too low dose may also have spotting

-studies have shown that if give large dose (2x more) in 1st year of continuous regimen you decrease amount of unpredictable spotting or bleeding

Indications for HRT

1. vasomotor symptoms

2. urogenital symptoms

3. osteoporosis ?

-used to be gold standard but not used anymore

-worked to maintain bone density and thought that had advantages for CVD

-however, cardiovascular disease not prevented for HRT and have better agents available to prevent bone loss

-so no longer 1st line for osteoporosis – i.e. not sole indication for using HRT

Evidence for use of HRT

1. HERS study

-given CEE and MPA to women with heart disease

-in 1st year had increased CVD in HRT group vs. placebo group -by year 4 had increased CVD in placebo group vs. HRT

-so if on HRT and have CVD don’t stop therapy because will do better over time

-but if not on HRT and have CVD don’t start because in the 1st year will have an increased risk

2. Other study on monkeys

-showed that Provera blunts estrogen’s positive effect on cardiovascular and prometrium does not

-took monkeys and fed high fat diet

-given E alone ( plaques small

-given E + Provera ( plaques were big

-given E + prometrium ( plaques remained small

-Provera does not seem to be greatest in terms of cardiovascular effects…

3. Study on women with CVD

-put on treadmill to see exercise endurance before getting chest pain

-women were given SL tablets of estrogen vs placebo

-women with SL tablets were able to exercise longer

-so estrogen seems to act like a vasodilator

-given Estrace + Provera ( not exercise as long

-given Estrace + Prometrium ( were able to exercise longer

-looks like Provera blunts CV effects that estrogen has and Prometrium doesn’t

-so after these studies started using Prometrium and not Provera

4. WHI study

-looked at healthy women

-showed 8 more women per 10000 got CVD on HRT

-showed 7/10000 more cases of breast cancer

-showed 30/10000 more cases of VTE (this was expected)

-study done in combo of Premarin and Provera

-separate arm of study in women with hysterectomy taking Premarin only (no Provera needed)

-this part is still going on

-so far have not shown that they have ( cases of CVD or breast cancer

-debate now of whether this is a Provera or estrogen causing effect

-according to Brown: this is a valid study

Conclusion of studies…

-prime indication of HRT is for symptoms (usually last 5 years) and quality of life improvements

-in general practice are telling patients to come off HRT and if they have bad symptoms they can restart HRT, if tolerable symptoms they do not need to go back on HRT

-no set way to take someone off HRT

-tell patients to taper over 2 weeks to 1month but no limit, can use any dose (i.e. every other day, cut patch, etc)

-should taper estrogen and stop both together at end (don’t need to taper progesterone)

-when starting women on HRT use Prometrium and not Provera.. because WHI study only looked at Provera effects (i.e. nobody showed that Prometrium has negative effects)

-may also see increased trend to using transdermal estrogen and Prometrium combinations

Contraindications to HRT

1. Active liver disease

2. Active VTE (not just history)

3. Personal history of breast cancer

4. Undiagnosed vaginal bleeding

5. Migraines especially with aura

Testosterone replacement

-provides sense of well being

-also used for libido

-used in women who have had oophorectomy

-libido= sense of desire, wanting to have sex

-so if women has no desire to have sex then give testosterone, but if problem is that she can’t have orgasm she does have sexual desire and testosterone is not indicated

-viagra may have role in supplying blood to clitoris to get more pleasure and have orgasm

-if it hurts during intercourse ( need Estring

-so can have someone one testosterone, Estring and viagra working on 2 different parts of sexual response

-not safe to use testosterone if CI to estrogen or if have hx of breast cancer because testosterone can be converted to estrogen in body

-SE of testosterone

-facial hair growth

-acne

-too much libido

-change in voice

Testosterone products available

1. Climaterone

-once monthly injection

-has E and T

-start with ~ 0.5 cc

-estrogen component may not be enough on its own

-may need to add 0.5 Estrace or 0.3 Premarin or patch or gel to help with vasomotor symptoms

-can also use DelEstrogen ( depo form of estrogen given every month and given with Climaterone

-may still need prn Estrogen in addition to DelEstrogen and Climaterone to help with hot flashes

-have evidence that works in menopause

2. Andriol

-40 mg po table taken every other day

-testosterone only

-no evidence that works in menopause but still prescribed

3. Compounded testosterone

-used for clitoral atrophy

-placed on external genitalia

-not used for libido (i.e. may work but not indicated for this)

Treatment of vasomotor symptoms without HRT

1. Progestin only products

-obese women have excess estrogen and are at risk of CVD and may need progestin only therapy for protection

-MPA ( 10mg bid

-Prometrium ( 300 mg daily

2. Venlafaxine ( 75mg daily

3. Phytoestrogens

-evidence based medicine does not show that it works

-may be due to placebo effect

-soybeans

-red clover

-tofu

-beer

4. Black Cohosh

-primary herb used in Germany

-compared to Premarin 0.625 and shown to be equivalent

-works for hot flashes… but still unregulated

5. Clonidine ( > 1mg /day

-but lots of SE so not used much

6. Gabapentin ( 300 mg/d or greater

-in 7 cases reported to treat hot flashes

7. Evening Primrose oil

-no better than placebo (RCT trial)

8. Don Quai

-no better than placebo (RCT trial)

9. Vitamin E ( 800 IU / day

-shown in breast cancer survivals to decrease hot flashes

-clinically it ( one hot flash per day

-may work and harmless so could recommend

Treatment of urogenital symptoms without HRT

1. KY Lubricants

2. Astroglide

3. Gynemoistris

4. Moisturizers

-Replena

-non hormonal used 2-3 times / week

-equivalent to Premarin vag cream for dryness

-pulls moisture into vagina – so don’t just use before intercourse

5. Increased sexual activity

................
................

In order to avoid copyright disputes, this page is only a partial summary.

Google Online Preview   Download