safety of vaginal estrogens?

[RobinP]

Sometimes I wonder how safe vaginal estrogens are? I worry that that residual drug application may contaminate other areas of the body, particularly the breast, if one is not extremely careful. Any comments on this potential estrogenic problem?

[Lani]

...
It is well known that atrophic vaginitis in postmenopausal women can be worsened or
induced by the use of aromatase inhibitors for the treatment of breast cancer. In fact, these drugs
exert their benefits on breast cancer by decreasing E2 biosynthesis, thus increasing the frequency
and severity of menopausal symptoms [28; 29]. In a recent study where seven breast cancer
patients treated with aromatase inhibitors received Vagifem (estradiol tablet) at a daily dose of 25
!g for 2 weeks and then, thereafter, twice weekly, serum estradiol (E2) rose from a median of 3
pmol/l to 72 pmol/l, at 2 weeks (range 3 to 232) [30]. Serum E2 levels generally decreased
thereafter to values of 40 pmol/l or less although values of 137 and 219 pmol/l were found at
weeks 7-10. A patient who received Premarin cream had serum E2 levels of 83 pmol/l at 2 weeks.
It should be mentioned that blood sampling for E2 measurement was done at time of patient’s
visit, a timing not likely to correspond to the highest levels of serum E2 after Vagifem
administration. It is thus more than likely that the values reported in [30] underestimate, up to an
unknown extent, the true elevation of serum E2 after Vagifem administration. The authors
concluded that the use of Vagifem with aromatase inhibitors is contraindicated. These findings
obtained in breast cancer women treated with aromatase inhibitors raise a serious issue about the
use of any vaginal estrogen preparation in postmenopausal women.
In previous studies with Vagifem, maximal and mean 24 h serum E2 concentrations were
measured at 180 ± 99 pmol/l and 84 pmol/l for the 25 !g dose while values of 81 ± 62 pmol/l and
40 pmol/l, respectively, were found for the 10 !g dose [30]. Other vaginal estrogen tablets and
creams have led to high or even higher serum estrogen levels [31-33].

[RobinP]

Thanks for the post. I see the level of serum estrogen increases, as I expected. I guess it is possible to to have estrogen cream accidentally placed on the breasts with contaminated hands after application, which I was trying to state in the first place. This dangerously could cause a situation of gynecomastia and hyperplasia, precursors of breast cancer.

[Donna]

Hi Robin and Lani,

I have both the Vagifem and Premarin cream in my medicine cabinet. Even though both my OB/GYN and my oncologist said they are safe and each recommended one over the other, I just didn't feel okay using them. It always sounded good while I was in the office, but when I got them home, something about taking them didn't seem right.

I pretty much follow my gut feeling on these things and I am gratified to find it backed up by science. I had stopped taking my bioidentical estrogen a couple of months before I was diagnosed just because all of the sudden it didn't feel right to use it anymore. Don't know why, but when I pay attention to my "gut" feelings, they usually pan out to be the right thing for me, sometimes despite recommendations to the contrary.

Now, if only I could get a "gut" feeling for the lottery :-)

Have a great day!

Donna

[AlaskaAngel]

Robin,

If a cream is used it should be applied only where intended. If the fingers are used there is some absorption even by the fingers, so immediately washing the hands with soap and water and minimal friction helps to minimize any stray absorption.

A.A.

[Becky]

My onc measured my estradiol level before starting Premarin cream and measures it at every visit. Absolutely no change whatsoever - even when I was using 1/2 g twice a week. Eventually I went to once a week and now it is every other Tuesday.

I was having so many bladder infections I couldn't tell anymore. When I wiped and there was blood, I'd look in the toilet and start my Cipro or Augmentin. Super frequent UTIs cause bladder cancer and this was more than a sex problem.

[MCS]

well there are several threads on this. even one started by me.

i am er negative and my estrogen levels are very low. i'm using vagifem but i feel like I playing russian rulette- what if my shot is the one that does affect my cancer.

so i'm going to use the remainder of the pack and i will not continue. I have no sex drive at all and no sex and this vagifem may help with the atrophy but who cares anyway if i'm not using it anyway!

I will have to explain this to the ob gym when I see him in 5 months. Oh lord!

love to all

maria

[dlaxague]

Hi Donna and everyone,

I respect "gut feelings" above all else. If your gut tells you otherwise, no amount of evidence or expert opinion can change that knowing of what's right for YOU. But connecting with gut or intuition or "small voice within" - there's the rub. It takes practice and distance from ego to achieve that connection.

Vaginal estrogen does get absorbed. Probably much better-absorbed from vaginal mucosa than from fingers that apply it so I'm not sure how important handwashing is. Skin is a wonderfully absorptive organ but the mucosa is even more-so. The vaginal estrogen that has shown the least systemic absorption is the Estring, but the consequence of that is that it's not the most effective at relieving symptoms, either.

Over time (a few days only), as the vaginal mucosa becomes more normal, more "fluffy", systemic absorption is less. Although they can measure minute systemic increases in estrogen (minooot, not 1/60th of an hour) from vaginal estrogen use, they cannot tell us that there is danger in that. Nor that there is no danger. All they know right now is that there is some small measurable change that happens systemically, and initially, when vaginal estrogen is used. Once again, not enough information on which to base our actions.

And regarding using vaginal estrogen to achieve "normal" intercourse - that is only one reason to use it. Another is to prevent cystitis (bladder infections). Long term, it may prevent or delay issues of incontinence and prolapse also.

So - we lack good research to tell us what is right. This kind of information will take awhile to accrue.

In any discussion of estrogen supplementation by any means, I am reminded of Susan Love's wonderings of long ago - noting that there is a big discrepancy between the level of benefit of hormone-limiting drugs (tamoxifen, AI's, faslodex) and the level of harm of using supplemental estrogen. Her thought was that this might because within the breast tissue itself, aromatase makes more estrogen than we can add with HRT and thus the effect of HRT is minimal (as shown by the big women's health (?-'can't at this moment remember the exact name) study). If she is right (and I think her theory is reasonable), then vaginal estrogen especially for those taking an AI or Tamoxifen would not significantly change the hormonal milieu within the breast. But we do not (yet) know this for sure.

Which brings us back to the gut (or intuition, or small voice within). To access that wisdom, we have to weed out the voices of ego, of fear, and of mind (which are all the same false voice). That weeding is of value regardless - thank you Donna, for the reminder to go for that voice, in whatever way suits us. Pray, meditate, sit in stillness, and get out of the way. Ask, but most importantly, listen.

Debbie Laxague

[R.B.]

General information on subject of topical hormone usage I came across whilst looking for something else
( PGE2 usage to induce birth )

Statistics on tamoxifen make thought provoking reading, and maybe more information would be helpful to those who have to weigh the competing pluses and minuses. - please see my previous posts.

http://www.library.nhs.uk/womenshealth/ViewResource.aspx?resID=237327&tabID=289

[AlaskaAngel]

http://pediatrics.aappublications.org/cgi/content/full/105/4/e55?ck=nck

[Hopeful]

Um, maybe this is stating the obvious, but I apply the cream with a Q-tip. None of it touches anything except the vaginal area.

Hopeful

[RobinP]

I think my question about contamination relates not just to application, which is an easy solution solver via hand washing,but to after application where one may touch the undergarments that may have contamination of Estrogen cream on it, cross contamination from partner's hands during intimacy, and etc. Yes, AA's article does explain how these creams can be dangerous to the breasts and that's why I'm concerned. Some think the estrogen micro environment of breasts has a bigger impact on causing bc than circulating blood estrogens.

[Hopeful]

My understanding is that it is unhealthful for men to have contact with the cream, therefore, not a good idea to be intimate with a partner on the day you use it or for a day or so afterwards. I am using a daub the size of my small fingernail on the end of a Q-tip at bedtime and there are no undergarments to be contaminated. I use panty-liners the next day and am careful what part of it I handle in removing it from my undergarment. If you went this route, you could also wear disposable gloves in handling the underclothing.

It is possible to avoid contamination if you exercise care and diligence.

Hopeful

[RobinP]

Well, is there any data to show the half life of estrogen cream, or how long it takes for it no longer to be evident where it was applied?

[AlaskaAngel]

A very good question for a qualified pharmacist, Robin. We can each ask one that we know, and see how well our answers match up!

Grin,

AlaskaAngel

[RobinP]

Hey, AA, I got to check out the PDR, as they usually give the half life of drugs. Anyway, I'll get back to you on this.

[dlaxague]

Two separate things are coming up here.

1. Caution in transmission of estrogen to others (studies about children of mothers using estrogen, sexual partners, etc).

2. Concerns about transmission of estrogen to the body that has just ingested the estrogen. Again, I'm not sure that having just applied estrogen to a mucous membrane (vaginally), we need to concern ourselves overmuch with touching any other area of our (own) body. It's kind of like trying to use a towel to get a dry spot on your windshield in the middle of a driving rainstorm. Although now I'm thinking - maybe a little stroking of the wrinkles about the eyes and mouth ... ? Do you think that would work (tic)? Am I the only one who noticed a pretty drastic increase in wrinkles and general sagginess, with AI use?

Seems to me that the answer, if you're that concerned about estrogen in your body, is not to put estrogen in your body in any way. I wish there were better answers to this whole issue of maintaining our bodies and our functions, without estrogen. But right now, they do not exist.

Debbie Laxague

[AlaskaAngel]

Hi Debbie. Are you saying that you have documentation supporting your contention that stray estrogen contact is of no additional physiologic concern in regard to breast cancer patients as long as they also use it vaginally?

A.A.

[dlaxague]

Hi Debbie. Are you saying that you have documentation supporting your contention that stray estrogen contact is of no additional physiologic concern in regard to breast cancer patients as long as they also use it vaginally?

No. I didn't realize that was the question. I thought that we were talking about the circumstance of possibly touching the applicator or suppository when applying vaginal estrogen, and then that finger absorbing estrogen and/or contacting some other body part that might absorb it.

I have no evidence either way. But if you're applying cream or suppository into a closed space lined with mucous membranes (vagina), I know that you are going to get higher systemic absorption from that than would be possible from any small residue left on your finger. Closed space and mucous membrane vs. open-to-air skin (hence prone to washing/rubbing/drying off) would seem no contest. Especially fingertips which seem more impervious (I don't know if that's true but it seems logical). We're talking about bits of residue from if you touched the applicator or the Estring and such, right? Not about taking the cream and intentionally smearing it around somewhere other than vaginally? The articles posted were, as nearly as I saw, not about vaginal estrogen creams anyway. The patches are INTENDED to be absorbed systemically and must have much higher doses than, say, estring, which is stated to provide the lowest dose of systemic absorption. My comment about wrinkles was labeled "tic" (tongue in cheek). I was joking. And I do wash my hands after inserting the Estring and using Estrace cream (tiny dollop).

Although again, I take it back to Susan Love's theory that supplemental estrogen (and she was talking of full-on HRT) made so little difference to risk because it's a drop-in-the-bucket to breast tissue that may be making its own estrogen via richly aromatase-enhanced cells.

And again again - measuring an increase in serum estrogen is not the same as proving that it's harmful. We are far from having good information to document risk OR safety.

Debbie

[RobinP]

AA, after thinking about it more, I think that it doesn't matter what the PDA says about the half life of estrogen because if the estrogen cream has not been absorbed, then it is still available as an active estrogen. I beginning to think that not only should estrogen be applied with an applicator or q-tip in only small amounts, but should be allowed to absorb into the vaginal tissues, then douched out after a period of so many hours after the vaginal mucosa has been rejuvenated with estrogen.

Estrogen is a double edged sword. On the one hand it is wonderful for bone health, skin, hair, libido, vaginal tone, urthra tone, etc. But on the negative side, it does have deleterious side effects, some effect caused even in small doses. I think that was what the article about gynecomastia in children and in men discussed. If even a small amount o estrogen cream on mammary tissue of a man or child can cause duct hyperplasia, the precursor of breast cancer, I'm sure it can in women too.

By the way, I find it interesting that the man, Dr. Pincus, who invented estrogen, many years ago, died of leukemia. It has been suggested that the chemicals, he spent years studying, caused his condition. I think he opened pandoria's box for himself and many.

No, I'm no posting all this to condemn those using vaginal estrogens or estrogens of any type, only to discuss and discover new insights to improve and sustain good health. I'm not telling anyone what they personally should do with estrogen cream. In the words of Margaret Sanger, the brainchild of birth control,"No Gods and No Masters" and that each woman be "the absolute mistress of her own body." Might l add, let each woman have the knowledge, seek the answers for her own mind to protect her own body from the substances that may harm, while allowing the substances that may heal.

[Hopeful]

Just an observation, here: if one of the purposes of using vaginal estrogen is to restore the body's own moisture through cellular health, douching is counterproductive.

Hopeful

[Becky]

Douching is a complete no-no to vaginal health in general because it disrupts normal vaginal flora and fauna and its natural lubrication.

It is the cause of many a bacterial or yeast infection.

Estrogen cream absorption on a thirsty vagina is immediate and great. The trick is lowering the amt of cream used to maintain health versus the amt you need to get healthy.

I went from 2X a week to once a week to now every other week. When tested 6 wks post first use, there was no difference in my estradiol reading vs pre using.

Don't douche for any reason ever!

[RobinP]

Thanks, Becky and Hopeful, being one who has never douched, I didn't realize the negatives aspects of it, and now after googling myself, I realize them. Boy oh boy, another rotten product offered to women- when does it end. You really got to educate yourself, read and read again.

Solution by Becky, thank you,"Estrogen cream absorption on a thirsty vagina is immediate and great. The trick is lowering the amt of cream used to maintain health versus the amt you need to get healthy." For those feeling they can control the cross contamination problem with this method, which seems plausable considering only a small amount is used and hopefully absorbed quickly, perhaps this is a good solution, probably with the best moisturizing results .Again, I'm not claiming any one solution is right for you. Just discussing all this to educate, open options, and let each decide for themself what is appropriate and acceptable.

Now another solution that I have found for those fearful of estrogn creams are natural herbal creams, Replens, vitamin E oil tablets squirted into the target area, soy/flaxseed preparations, etc.- though I don't know the effectiveness of these products, myself. However, a friend on another board swears by REPLENS being helpful. She's estrogen positive and is fearful of any extra estrogen on board. Perhaps using Replens and natural remedies between periodic estorgen cream use may be another solution to help reduce estrogen cream use for those concerned.See link below for mANY VAGINAL NATURAL REMEDIES. http://www.hisandherhealth.com/index.php?Itemid=84&id=317&option=com_content&task=view

[Hopeful]

Robin,

I started out with Replens at the suggestion of my gyn, but it is limited in what it can do for those thinning tissues. She admitted to me that estrogen treatment was the way to get them back into health. I have been following a similar course to Becky, starting out with a daub every three days that is now up to bi-monthly (I have to do it on fixed days or else I lose track). In addition, I supplement with Replens every three days. I have found using both to be the most useful.

When I started on Estrace, my gyn had me doing blood work once a week for a month. My base line for ER was below the lab detection level after 6 months on an AI. It went up somewhat after the first week, though never above the level for post-menopause, and came down in suceeding weeks, even as I continued to use it. It leveled out at the end being either below the lab detection level or just above it. My gyn and onc are very satisfied. The gyn explained that as the tissue became re-epitheilialized, it would more readily absorb the estrogen. At the last exam prior to my starting the cream, my gyn could not fully insert a speculum and doubted her ability to collect enough cells to do a pap smear. The exam was uncomfortable this time, but she was able to do it properly, visualize the cervix and do a proper cell collection. This medication is part of my current health plan now.

FWIW, my onc said that he believes the ER levels "bounce around" some on their own without the use of any of these creams, even while on AI's. He rolled his eyes at the weekly blood draws, but I did them anyway. The results gave me confidence to continue with both treatments.

Hopeful

[RobinP]

Excellent approach, HOPEFUL, thanks for sharing, I know it helps alot of us here on her2. ALSO, I appreciate what you posted earlier about methods used to help prevent cross contamination.

[Becky]

Another product that is helpful is RepHresh (by the same people who make Replens). This product is just like Replens but it is buffered and helps normalize vaginal pH. Atrophic vagina due to "menopause" is also acidic. Acidic conditions can also give rise to yeast or other infections so an atrophic vagina is a "twitchy" vagina. Besides the pH being off, there are less vaginal secretions to "wash" away pathogens. I was also subject to this (yeast) and yeast is difficult to get rid of sometimes because adding estrogen can further enhance things. Also, one can be allergic to formulation ingredients (in the estrogen cream/suppository/ring, the yeast infection cream, Replens etc). The usual suspect is usually the preservative but propylene glycol can be a culprit too. These conditions are enhanced by a raw, dry vagina.

If you also have bladder problems, then its worse because antibiotics bring on the yeast (or you can ping pong a bladder infection to a vaginal infection). It can be quite a balancing act to get it all right and be okay. Sometimes the estrogen cream isn't the find all cure and you really have to play around with alot of elements.

It took me almost 2 years to get it all right. I am always on the "edge" but I'm pretty balanced right now. Its helpful to have a great gyne who listens to you and works with you and an great onc too.

[Hopeful]

Becky,

At my last visit, my gyn asked me if I noticed "residue" from the Replens. I told her I did, and she said it was a common complaint. Is there a difference with RepHresh?

Hopeful

[Becky]

Dear Hopeful

When I use RepHresh, I can only use one tube once in awhile (because I am affected by being sensitive or allergic to a common component of these type products). However the gelling agent (Carbopol) is a powder in its natural form (as a chemist I was a formulator for personal care products and this is a common thickener as it forms a clear gel whereas others do not). So, when the product comes out and is on the outside of the vagina then dries up a bit, this could certainly happen (but I do not notice it as I only use 2 tubes a month - but using a tube every 3 days as recommended - one would end up noticing sooner or later). Another problem with Carbopol is that it can also be tacky which is why it usually isn't used in skincare products and only in haircare products (when used outside the body).

[dlaxague]

Dear Becky,

A chemist, huh? I'd never thought about what ELSE is in something like estrogen creams which is odd because I carefully read the labels of things like moisturizing lotion, wanting to avoid parabens. So there it is on my Estrace tube - a long list of chemicals including parabens. However I guess since they are under suspicion for the estrogen-like effects (I think?), their presence in an estrogen cream is less significant. Here's what ELSE is in Estrace:

propylene glycol, stearyl alcohol, white ceresin wax, mono-and di-glycerides, hypromellose, sodium lauryl sulfate, methylparaben, edetate disodium, and t-butylhydroquinone.

And we're putting that inside our bodies. As a chemist, do you see any red flags there, apart from the parabens? Do you think that some of these chemicals have not been sufficiently studied to know if they are safe? At least it's not like lotion, applied daily over large surfaces?

Debbie

[Becky]

Debbie

In parathesis behind each ingredient is what that ingredient does. For the record, estrogen (and all sex hormones) are highly lipophillic (fat loving and water hating). They are waxy substances that are synthesized in the body by further reacting cholesterol.


propylene glycol (humectant - keeps the cream moist and it also is a cosolubilizer), stearyl alcohol(emulsifier), white ceresin wax(emulsifier), mono-and di-glycerides(stabilizers for waterless systems), hypromellose(thickner), sodium lauryl sulfate (surfactant - pretty heavy duty anionic - I am surprised this is in there since there is no water in the formulation. This is the active ingredient in most shampoo), methylparaben(preservative), edetate disodium(chelate - binds heavy metals as it could degrade the estrogen), and t-butylhydroquinone(antioxidant but I am surprised they didn't use Vitamin E).


Premarin cream has no preservative (per se) it uses cetyl and benzyl alcohol that play double duty as preservatives and solubilizers. No chelate (usually metal contamination comes from water - iron, magnesium etc) but it still has the sodium lauyl sulfate and propylene glycol (as well as glycerine).

Damned if you do and damned if you don't! Party on.

[Hopeful]

Wow, Becky, thanks for both posts - very enlightening.

Hopeful

[AlaskaAngel]

When I resorted to using the Estring, it did work well at least for all the "outer" dryness problems outside the vagina, and helped slightly with the dryness in the vagina. Whenever I took it out to change it, if I didn't replace it with a new one right away, every time things went right back to being uncomfortably dry.

But the last time I used it (many months ago) and took it out to replace it, I went for over a month without the vaginal and perineal dryness recurring. However, within a few days of taking it out I still could feel the usual dryness problems elsewhere -- my eyes and ears were painfully dry again and the rest of my skin was very very dry. So I'm puzzled as to why that would happen.

A.A.