Questions about Estrogel for our HRT experts

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Questions about Estrogel for our HRT experts

Postby Amy Farrah Fowler » Tue Dec 05, 2017 8:38 pm

I have an extreme sensitivity to medical adhesive. Because of all the risks of oral estrogen, and not 100% trusting the safety of sublingual administration (how much is accidentally swallowed intact, for example?), I am considering switching to transdermal cream from my patches. I have some questions & concerns, and there are members here who've done quite a lot of research I hope they'll share with me here.

The patches always started to peel themselves off after a day or two (sometimes just a bit longer in colder weather), forcing me to apply pressure several times a day to get them to re-stick. After 1-2 days, I've had to resist the urge to scratch. I recently bought a box with a 6-month supply of Tegaderm transparent bandages larger than the patches, applied over them to keep them firmly attached longer. It usually works, but by day 2 I'm fighting an urge to scratch that's almost unbearable. The patches are still soaking wet underneath when I remove them; the raised welt left by the adhesive ring of the patch is now joined by a larger raised welt of irresistibly itchy skin that had been in direct contact with the Tegaderm. The affected area remains angrily red then pink up to a week. Sometimes I scratch until I break the skin.

I've historically ended up with serum estradiol levels as high as 156 pg/mL, but usually about 65-95 pg/mL, using a 7-day 100-mcg patch, changed twice a week because of my skin sensitivity (so I can relieve the spot under the patch sooner). My doctor was about to suggest, being post-op, it was time to reduce my dosage when I pointed out my serum level. He said, you're right, your level isn't very high. We can leave it.

The patch dispenses 100 mcg of estradiol over a 24-hour period every day it is worn. Out of that, I get a blood level under 100 pg/mL (but several times the level necessary to prevent bone density loss).

1 pump of an Estrogel bottle dispenses 75 mcg of estradiol. I don't know how much of it can sweat off or wash off once it's applied and has dried--particularly relevant with my half my forearms buried in dishwater for hours each day. I know the cream is magnitudes less convenient & more time-consuming than patches. But relief from the itching, scratching, welts, detachment & extra adhesive would be worth it--IF Medicaid will cover the gel as it has the patches, and in the past, the pills.

Is there a direct functional equivalence, mcg for mcg, of patches & cream? In substituting a 75-mcg daily pump for a 100-mcg patch every few days, might I need two pumps to meet or exceed the patch's effects?

Is there anything else I might need to know before discussing this change with my doctor?

And are there any studies or reports I should know of about sublingual administration (and how many mg a day would be equivalent to my patches) safety & efficacy, with any notes about accidental swallowing?
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Re: Questions about Estrogel for our HRT experts

Postby Kay » Wed Dec 06, 2017 12:35 pm

Amy Farrah Fowler wrote:Because of all the risks of oral estrogen, and not 100% trusting the safety of sublingual administration (how much is accidentally swallowed intact, for example?)


Several studies show oral estradiol to be quite safe in contrast to other forms of oral estrogen. I've taken high doses (12-14 mg daily) in the past, doctors weren't concerned. The effect on clotting is much less marked as well on blood pressure and stroke risk. Studies have even shown its (cardiovascular) benefits in women taking 2-4 mg oral estradiol daily.

I am considering switching to transdermal cream from my patches. I have some questions & concerns, and there are members here who've done quite a lot of research I hope they'll share with me here.


Cream doesn't absorb well and serum levels of E2 will be VERY low. Waste of money.

My doctor was about to suggest, being post-op, it was time to reduce my dosage


What's the difference post-op? Your T was suppressed pre-op too and just as low. Why would E suddenly be reduced post-op?

1 pump of an Estrogel bottle dispenses 75 mcg of estradiol. I don't know how much of it can sweat off or wash off once it's applied and has dried--particularly relevant with my half my forearms buried in dishwater for hours each day.


Studies have shown 4 pumps of Estrogel yield about 100-200 pg/ml estradiol. On 4 pumps, my levels 12 hours after application, were 200 pg/ml. I'm on 6 pumps right now.

Is there a direct functional equivalence, mcg for mcg, of patches & cream?


Go by feel, if you feel as good, if body responds the same. But a 100 mcg patch is usually equal to 2 mg oral estradiol equal to about 2-4 pumps of estrogel. You can start with 2 pumps a day, if not enough, 4 pumps.

And are there any studies or reports I should know of about sublingual administration (and how many mg a day would be equivalent to my patches) safety & efficacy, with any notes about accidental swallowing?


Just swallow. Or take same dose sublingually. Overthinking....bio-estradiol is quite safe. :)
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Re: Questions about Estrogel for our HRT experts

Postby Amy Farrah Fowler » Wed Dec 06, 2017 4:15 pm

Kay wrote:
Amy Farrah Fowler wrote:Because of all the risks of oral estrogen, and not 100% trusting the safety of sublingual administration (how much is accidentally swallowed intact, for example?)


Several studies show oral estradiol to be quite safe in contrast to other forms of oral estrogen. I've taken high doses (12-14 mg daily) in the past, doctors weren't concerned. The effect on clotting is much less marked as well on blood pressure and stroke risk. Studies have even shown its (cardiovascular) benefits in women taking 2-4 mg oral estradiol daily.


Can you provide any citations?

Kay wrote:
Amy Farrah Fowler wrote:My doctor was about to suggest, being post-op, it was time to reduce my dosage


What's the difference post-op? Your T was suppressed pre-op too and just as low. Why would E suddenly be reduced post-op?


E2 is usually prescribed at higher levels pre-op even with spiro, with the view that post-op, it has less T to overcome, and there is no reason to maintain riskier levels. I disagree to the extent that many clinics suggest 5-7 (even 10) years of feminization-level estradiol, regardless of how soon after starting one has an orchiectomy, and only then reduction to maintenance levels. The typical target is 150-200 pg/mL.

Pre-HRT, my testosterone was nearly 700 ng/dL, then early on in HRT, I managed to get it just under 30. Post-op, it's been 14-21. I still take 5 mg finasteride daily so far. My free T has dropped from 6 to 3 pg/mL.

Kay wrote:
Amy Farrah Fowler wrote:And are there any studies or reports I should know of about sublingual administration (and how many mg a day would be equivalent to my patches) safety & efficacy, with any notes about accidental swallowing?


Just swallow. Or take same dose sublingually. Overthinking....bio-estradiol is quite safe. :)


I know that nearly all studies showing health risks were done with conjugated estrogens or ethinyl estradiol, but considering every family member who's died has died of a clot, male or female, HRT status unknown (but some before menopause), most not far from my age, my morbid obesity, hypertension, diabetes, and heart arrhythmia all considered, and my nonsmoking status & anticoagulant med notwithstanding, I want to avoid the first-pass effect with the liver above all.
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Re: Questions about Estrogel for our HRT experts

Postby Kay » Thu Dec 07, 2017 10:51 am

Kay wrote:
Amy Farrah Fowler wrote:
Several studies show oral estradiol to be quite safe in contrast to other forms of oral estrogen. I've taken high doses (12-14 mg daily) in the past, doctors weren't concerned. The effect on clotting is much less marked as well on blood pressure and stroke risk. Studies have even shown its (cardiovascular) benefits in women taking 2-4 mg oral estradiol daily.


Can you provide any citations?


Of course. :)

Journal of Obstetrics and Gynaecology
Volume 14, 1994 - Issue 5


“The urinary metabolites of prostacyclin and of its counterpart, thromboxane, were determined in 40 postmenopausal women who had been treated with transdermal or oral oestrogen for 4 weeks. With oestradiol valerate administered by mouth there was an increase in prostacyclin metabolites. A decrease in thromboxane metabolites was observed only with transdermal oestradiol. Thus, both oral and transdermal oestrogen had positive effects on the prostacyclin thromboxane ratio. This may be one of the biochemical actions by which oestrogen has a beneficial effect on the cardiovascular system in postmenopausal women.

Circulation. 1987 Oct;76(4):753-8.

“We conclude that both oral and percutaneous treatment with estradiol may provide protection against the age-related increase in diastolic blood pressure observed in early postmenopausal women.”

Ann Clin Res. 1983;15 Suppl 38:1-121.
Blood pressure and hemodynamics in postmenopausal women during estradiol-17 beta substitution.


https://www.ncbi.nlm.nih.gov/pubmed/6367617

"Blood pressure, central hemodynamics and peripheral blood flow were measured at rest in 20 normotensive and 20 hypertensive postmenopausal women during cyclic placebo/estradiol-17 beta treatment. Micronized estradiol-17 beta was given in daily doses of 2 mg and 4 mg. Corresponding measurements were also performed during exercise in 10 borderline hypertensive subjects given estradiol-17 beta substitution in 2 mg daily doses for three months."

"Estradiol-17 beta substitution decreased the systolic and diastolic blood pressure in normotensive, hypertensive and borderline hypertensive postmenopausal women."

"Irrespective of the pretreatment blood pressure levels, heart rate decreased during estradiol-17 beta substitution"

"Estradiol-17 beta substitution caused an increase in the blood volume in all groups of postmenopausal women"

"Cardiac output increased in the normotensive test subjects but decreased in the hypertensive and borderline hypertensive subjects"

JAMA. 2009 August 19; 302(7): 774–780.

"We (...) conducted a randomized phase 2 trial in postmenopausal women with hormone receptor-positive, AI-resistant advanced disease to compare 30-mg estradiol daily (10 mg t.i.d.) with 6-mg daily (2-mg t.i.d.)"

“the mean [standard deviation] trough levels of estradiol at one month were 302 [519] pg/mL on the 6-mg arm and 2403 [2268] pg/mL on the 30-mg arm (P <.001)”

“The rate of thrombosis was low with one event on each arm of the study.”

Arm: 34 people in 6 mg oral; 32 people in 30 mg oral
Median age: in 6 mg, 54.7 yrs old ( 36.3-83.8 ); in 30 mg, 59.5 yrs old (39.4-77.7)

Clin Ther. 2009;31 Pt 2:2371-8.

"Twenty-two patients received estradiol 10 mg TID (30 mg total administered as 2-mg tablets) and the 2 most recently treated patients received estradiol 2 mg TID (6 mg/d), based on data recently presented by Ellis et al.11 All patients were encouraged to take enteric-coated aspirin 81 mg/d. The patients’ demographic and clinical characteristics are shown in Table I. All 26 patients were female (median age [at the time of estrogen therapy], 59 years; range, 42–92 years).”

"a patient who developed a venous thromboembolism that was thought to be study drug–related was treated with the lower dose of estradiol.”

SUMMARY OF TWO STUDIES: on 30 mg oral E2, 54 women aged 40-92 yrs old. Only 1 case of thromboembolism. Despite advanced age and cancer. Time of treatment: 6-22 months

Oncologist. 2014 Nov;19(11):1127-8.

“Patients were initially treated with 6 mg/day estradiol”

“Thirteen patients were evaluable for toxicity and response. No grade 3 or 4 toxicities were observed.”

Women aged 49–85 (median 68 yrs).

SUMMARY OF THREE STUDIES: on 6 mg oral E2, 49 women aged 36-92 yrs old. Only 2 cases of thromboembolism. Despite advanced age and cancer.

J Clin Endocrinol Metab. 2012 Dec;97(12):4422-8

“oral estradiol valerate, in combination with GnRH analogs to suppress testicular function if
the plasma testosterone level was not in the female range at a 4-mg dose of estrogen.”

Table 4

Out of 163 transsexual women on estradiol valerate, 0.6% incidence of thromboembolism.

Maturitas. 1980 Jul;2(2):95-100.

“The material consisted of 32 patients, 12 of whom were selected for control. All were cases approaching the menopause and had been subject to oophorectomia bilateralis and hysterectomia for myomas. All 20 investigation patients received estradiol valerianate orally 4 mg/day of 6 mth. During the course the serum estradiol level increased 5--6-fold from the postmenopausal levels. No significant changes occurred in the serum triglycerides and total cholesterol, whereas in the control group the triglycerides decreased. The proportional concentration of beta-lipoproteins decreased. There was also a slight decrease in the pre-beta-lipoproteins. The proportional concentration of beta-lipoproteins increased, as also serum high density lipoprotein (HDL) cholesterol. In the liver enzymes no changes occurred. Blood pressure increased in one patient. There were no other complications.”

(mean age 46.9 yrs old, range 35-53)

“During treatment no permanent changes were observed in serum ALAT- and y-GT-values”

Exp Clin Endocrinol Diabetes. 2005 Dec;113(10):586-92.

"Sixty male-to-female transsexuals were treated with monthly injections of gonadotropin-releasing hormone agonist (GnRHa) and oral oestradiol-17beta valerate for 2 years to achieve feminisation until SRS."

"Two side effects were documented. One, venous thrombosis, occurred in a patient with a homozygous MTHFR mutation. One patient was found to be suffering from symptomatic preexisting gallstones. No other complications were documented. Liver enzymes, lipids, and prolactin levels were unchanged."

The treatment included 6 mg oral estradiol valerate and 3.8 mg goserelin acetate every four weeks. The only DVT complication was seen in an individual with a pre-existing condition/genetic mutation, in a 62 yr old TS woman, oldest of the group. Out of 60 people.

Estradiol levels ranged from 325-1183 pmol/L, at 12-24 months.
Average age was 38.37 yrs old (SD 11.36).

BMJ. 2012 Oct 9;345:e6409.

"The women in the treated group with an intact uterus started treatment with 2 mg synthetic 17-β-estradiol for 12 days, 2 mg 17-β-estradiol plus 1 mg norethisterone acetate for 10 days, and 1 mg 17-β-estradiol for six days (Trisekvens; Novo Nordisk, Denmark). In women who had undergone hysterectomy, first line treatment was 2 mg 17-β-estradiol a day (Estrofem; Novo Nordisk, Denmark)."

“At inclusion the women on average were aged 50 and had been postmenopausal for seven months.”

After 10 years of randomised treatment, women receiving hormone replacement therapy early after menopause had a significantly reduced risk of mortality, heart failure, or myocardial infarction, without any apparent increase in risk of cancer, venous thromboembolism, or stroke.

Menopause. 2006 Jul-Aug;13(4):643-50.

“Oral E(2), with or without NETA, produced no net activation of coagulation but improved fibrinolysis.”

Fertil Steril. 1997 Sep;68(3):449-53.

« Compared with placebo, oral E2 replacement therapy resulted in a significant decrease in fibrinogen and apo B and a significant increase in plasminogen.”

Patient Prefer Adherence. 2013; 7: 607–619.

“Estradiol itself has a lower impact on estrogen-hepatic proteins, and is more readily metabolized by the liver”

Minerva Ginecol. 2014 Feb;66(1):91-102.

“Micronized estradiol (E2) and its estere valerate (EV), is more easily metabolized by the liver (…). This causes minimal metabolic impact”

Amy Farrah Fowler wrote:E2 is usually prescribed at higher levels pre-op even with spiro, with the view that post-op, it has less T to overcome


Wrong. There isn't less T post-op because spiro and other anti-androgens (+estrogen) strongly suppress T pre-op, even sometimes more strongly than post-op. Many transwomen actually report increased symptoms of masculinization (breast atrophy, increased oiliness/hair growth, etc.) post-op, myself included.

and there is no reason to maintain riskier levels.


On bio-identical estradiol, especially if taken non-orally, the risks are negligible and the benefits, several.

The typical target is 150-200 pg/mL.


Based on absolutely no science at all and an average in premenopausal women with a total disregard for:

- pregnancy levels in premenopausal women which would significantly change that average
- the fact that the average today seen in ciswomen may not be ideal after all since traditionally, women had many more pregnancies
- the fact that ciswomen are a radically different population insofar as: ciswomen developed and feminized with no prior exposition to high levels of androgens, at a time when growth hormone levels were much higher and many other factors were different (i.e. telomere length), and also might be more sensitive due to a different hormonal environment in-utero. The proof: breasts begin to significantly grow in girls at VERY low levels of E2 (before menarche), we know that at such low levels there would likely be absolutely no growth in transwomen since even at higher levels, results have been, in general, quite poor in contrast to ciswomen.
- estradiol levels fluctuate in time so blood tests are not reliable anyways

Also,

Lancet Diabetes Endocrinol. 2017 Apr;5(4):291-300.

“The precise concentration of oestradiol that results in adequate feminisation with the lowest risk of complications is not known.28”

Pre-HRT, my testosterone was nearly 700 ng/dL, then early on in HRT, I managed to get it just under 30. Post-op, it's been 14-21. I still take 5 mg finasteride daily so far. My free T has dropped from 6 to 3 pg/mL.


Your total and free T may have dropped post-op but you forget to realize that Spiro pre-op BLOCKS T so that a significant amount of T, even if slightly higher pre-op, was blocked by Spiro.

Amy Farrah Fowler wrote:I know that nearly all studies showing health risks were done with conjugated estrogens or ethinyl estradiol, but considering every family member who's died has died of a clot, male or female, HRT status unknown (but some before menopause), most not far from my age, my morbid obesity, hypertension, diabetes, and heart arrhythmia all considered, and my nonsmoking status & anticoagulant med notwithstanding, I want to avoid the first-pass effect with the liver above all.


I agree even if risk is low with oral E2, best to go with transdermal. :)
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Re: Questions about Estrogel for our HRT experts

Postby Michi » Fri Dec 08, 2017 7:50 pm

I found the Alvogen patches to be the best. I take them off when I take a shower and put them back on. They stick well for me. I've had my Mylan and some other brand I can't remember. They are available at Walmart, just in case you want to try something different, if a gel didn't work. I did ask the same question as you and got the answer you could probably search if you want to. I know they say they delivered over a week. But I don't believe that. When I first got them, I put them on my bicep and I could taste it.
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Re: Questions about Estrogel for our HRT experts

Postby Amy Farrah Fowler » Fri Dec 08, 2017 10:09 pm

Michi wrote:I found the Alvogen patches to be the best. I take them off when I take a shower and put them back on. They stick well for me. I've had my Mylan and some other brand I can't remember. They are available at Walmart, just in case you want to try something different, if a gel didn't work. I did ask the same question as you and got the answer you could probably search if you want to. I know they say they delivered over a week. But I don't believe that. When I first got them, I put them on my bicep and I could taste it.


I can only get whatever generics or brands are on Medicaid's preferred list formulary--or on its pre-approval list with sufficient justification. The only transdermal E2 on the preferred list is a generic for Climara. All the gels & creams are on the ask-us-first-and-we'll-see list.

Oral Estrace is also preferred (the sublingual option).
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