Oral vs Transdermal Administration

Transdermal estrogen therapy is the choice in the

following patients:
1. High-risk women have VTE
2. Women with spontaneous hypertriglyceridemia
or estrogen-induced hypertriglyceridemia
3. Obeseitas women with metabolic metabolism

Transdermal estrogen therapy must be approved in

smokers, women with hypertension, and choices
for women with sexuality disorders
The Vaginal Administration of Estrogen
– Very Low-Dose Method
• Rapid absorption -> estrogen level in the
circulation rises -> after the vaginal mucosa is
mature, absorption decreases decrease occurs
+ 3-4 months
• Giving: 0.3 mg conjugated estrogen, 2-3 x / week
• The measurement of vaginal pH can be used
adequately for this treatment: acidic pH (<4.5)
correlates with the effects of good estrogen
• Giving vaginal creams> 6-12 months requires
observation of endometrium
The Vaginal Administration of Estrogen
– Standard Dose Method
• Vaginal ring that releases 50 or 100 mg of
estradiol acetate per day for a duration of 3
months
• The level of estradiol achieved in the blood is the
same as that achieved from oral or transdermal
administration
• The systemic levels obtained can effectively
suppress hot flush, and benefits for bone can also
be expected
• The use of a progestin can be used to protect
endometrium if the uterus is still presen
 Estradiol Implants
• Estradiol pellets are available at doses of 25,
50 and 75 mg for sub-cutaneous
administration twice a year
• Giving with a dose of 25 mg reaches levels in
the same blood as oral administration (40-60
pg / mL), but after several years the level of
use can be 2-3 x higher need to monitor
blood estradiol levels, if levels> 200 pg / mL ,
the giving interval is extended
 Percutaneus estrogen
• Transdermal estrogen can also be given with
gel or spray
• Like the pellet, blood estradiol levels need to
be monitored and maintained <100-200 pg /
mL
• Comparison data with other routes is not
available
 Monitoring Estrogen Dosage with
Estradiol Blood Levels
• Measuring blood estradiol levels is very useful
in certain patients, such as patients who have
asked to increase estrogen doses to deal with
their complaints target the target range: 40-
100 pg / mL, when very high blood estradiol
levels can be diagnosed psychosomatically
• FSH levels cannot be used to monitor estrogen
doses because FSH is regulated by other
factors besides estrogen
 Estrogen-Progestin Sequential and
Continuous Regimens
• The addition of progestin with a daily dose of estrogen provides a protective effect against
endometrial hyperplasia, and makes amenorrhea within 1 year after treatment in 80-90% of
patients
• In sequential regimens, estrogen is given daily and progestin for 2 weeks every month with a
progestin dose:
5 mg medroxyprogesterone acetate, or
0.7 mg norethindrone, or
1.0 mg norethindrone acetate, or
200 mg micronized progesterone
• In a daily combination regimen, progestins are combined with estrogen with a dose:
1.5 or 2.5 mg medroxyprogesterone acetate, or
0.35 mg norethindrone, or
0.5 or 1.0 mg norethindrone acetate (0.1 mg dose is available), or
100 mg micronized progesterone or
2 mg drospirenone or
2 mg dienogest.
• This hormone regimen is combined with calcium (500 mg) and vitamin D supplementation (1000-
2000 IU / day)
• Later the use of postmenopausal therapy was used with lower doses
before the standard dose for estrogen was 0.625 mg conjugated estrogen,
1-2 mg micronized estradiol, 1-2 mg estradiol valerate, or equivalent doses
of other estrogens such as 5 µg ethinyl estradiol
• Lower doses have been shown to be as effective as the previous standard
dose tadi conjugated estrogen with a dose of 0.3 or 0.45 mg is also
effective in obtaining bone density when combined with 1.5 mg MPA, and
a dose of 0.5 mg micronized estradiol also produces the same effect
• Doses of 0.45 / 1.5 mg and 0.3 / 1.5 mg of conjugated estrogen / MPA
combination can overcome vaginal atrophy and reduce hot flush and
improve sexual function as well as combination use with a dose of 0.625 /
2.5 mg, ethinyl combination estradiol and norethindrone acetate (2.5 µg /
0.5 mg) are also as effective as higher doses (5.0 µg / 1.0 mg) to treat hot
flush
• The advantages of this lower dose: less mastalgia, less breakthrough
bleeding, higher rate of cumulative amenorrhea, retain the favorable
changes in the lipid profie
 Progestational Side Effects
• Some side effects such as breast tendernsess, bloating, and
depression
• Mastalgia was found in 28.7% of women taking
combination estrogen-progestin therapy
• The question arises bisa can progestin administration be
further minimized to reduce these side effects? -> the risk
of bleeding and endometrial / endometrial hyperplasia is
higher due to the effect of unopposed estrogen
• an endometrial monitor is needed if you want to extend
this progestin administration cycle -> Annual endometrial
biopsy is recommended for estrogen users who get
intermittent progestins
• Some patients are very sensitive to MPA -> can be
overcome by replacing it with norethindrone
• In the sequential regimen, a dose of 0.7 mg
norethindrone (available on progestin only,
contraceptive oral minipil, each pill contains 0.35
mg norethindrone)
• In the combination daily regimen, the dose of
norethindrone 0.35 mg / day -> available
preparations containing a combination of
estradiol and norethindrone acetate
• The use of vaginal gel with very low doses can
effectively protect the endometrium giving 90
mg every 2 days giving changes to the secretory
endometrium
• The use of 4% preparations twice a week protects
the endometrium and is associated with
amenorrhea
• In sequential regimens, 4% preparations must be
given every day for at least 14 days per month
• Use of a transdermal estrogen-progestin
combination -> norethindrone acetate with a
daily dose of 0.140 or 0.250 mg, or
levonorgestrel with a daily dose of 0.007,
0.015, 0.030 and 0.040 mg / day; and in the
sequential regimen: 0.250 mg or
levonorgestrel 0.010 mg
 The Progestin Intrauterine Device
• IUS LNG-releasing contraception has been remade with
a smaller model (not yet available) which releases 10
µg levonorgestrel per 24 hours; but a larger LNG IUS
(Mirena) can also be used in postmenopausal women
• The presence of intruterine progestins effectively
protects the endometrium from hyperplasia and ca
• LNG IUS has the advantage of using with a duration of
10 years
• This method is an option to minimize (if not total) the
systemic effects of progestin
Treatment Options for Hot Flushes
• Treatment options for vasomotor symptoms
are hormone therapy, but there are a number
of women who cannot get this hormone
therapy
• Other therapeutic options used before this
only give a slight increase in vasomotor
complaints and some even cause adverse side
effects
• In recent years, selective serotinin reuptake
inhibitors (SSRIs) have been used and have a
significant effect on hot flush
• Medications that have been studied include
citalopram (Celexa), fluoxetine (Prozac), sertraline
(Zoloft), paroxetine (Paxil), and serotonin and
norepinephrine reuptake inhibitors, venlafaxine
(Effexor) and desvenlafaxine succinate (Pristiq)
• In addition, anti-seizure drugs, Gabapentin
(Neurontin) have also been shown to reduce
vasomotor complaints
• SSRIs are the best choice after hormone therapy,
although the reduction in hot flush achieved is not as
good as that obtained with estrogen therapy
• It is better to try with a low dose given that it can
reduce libido, and increase the dose slowly
• An additional benefit of SSRis is that it can also reduce
depression, anxiety, and sleep deprivation
• Paroxetine, fluoxetine, and sertraline are better
avoided in women treated with tamoxifen because
they are associated with a risk of death from breast
cancer