for those considering using or using estrogen containing vaginal creams or pills
 

Menopause. 2008 Sep 26. [Epub ahead of print]

Effect of one-week treatment with vaginal estrogen preparations on serum estrogen levels in postmenopausal women.

Labrie F, Cusan L, Gomez JL, Côté I, Bérubé R, Bélanger P, Martel C, Labrie C.
From the Oncology and Molecular Endocrinology Research Center, Laval University Hospital Research Center (CRCHUL) and Laval University, Quebec, Canada.
OBJECTIVE:: Approximately 50% of postmenopausal women suffer from vaginal atrophy, and a large proportion of them choose intravaginal estrogen preparations administered for local action to avoid systemic exposure to estrogens and its associated risk of breast and uterine cancer. The primary objective of this study was the evaluation of the systematic bioavailability of estradiol and estrone and the pharmacokinetics of two of the most frequently used intravaginal estrogen preparations, namely Vagifem and Premarin cream. DESIGN:: While immunobased assays could not previously provide accurate measurement of serum estrogen concentrations in postmenopausal women, we have used validated mass spectrometry assays to measure the pharmacokinetics of serum estradiol and estrone during the 24 hours following the seventh daily application of 25 microg estradiol (Vagifem) and 1 g (0.625 mg) conjugated estrogens (Premarin) cream in 10 postmenopausal women in each group. RESULTS:: Serum estradiol was increased on average by 5.4-fold from 3 to 17 pg/mL during the 24-hour period after daily administration of 25 mug estradiol or 1 g (0.625 mg) conjugated estrogens cream. Serum estrone, conversely, increased 150% with Vagifem and 500% with Premarin cream. CONCLUSIONS:: The present data using validated, accurate, and sensitive mass spectrometry assays of estrogens show that the Vagifem pill and Premarin cream, after 1 week of daily treatment, cause an approximately fivefold increase in serum estradiol in postmenopausal women, thus indicating that the effects are unlikely to be limited to the vagina and that systemic actions are expected after application of these intravaginal estrogen preparations.
PMID: 18820592 [PubMed - as supplied by publisher]

Thank you for posting this. I know that my onc and gyno were both not sure of the systemic effects. I would like to know if you have any information about whether or not a person with er/pr- should be concerned about estrogen for the primary tumor and also what chances we have of having a secondary cancer that is er/pr+?

If I read this right, I think I am really glad that we have stuck to Estrace...

Estrace - I use it too but "heard" this study differently
 

Brenda said: "If I read this right, I think I am really glad that we have stuck to Estrace..."

Hmm. I dunno. The only reason Estrace wasn't implicated was that they didn't study it. I'd assume that its absorption would be just as bad (or good, depending upon your perspective). I started with Estring which at that time had shown the smallest systemic absorption. But over the years that just wasn't cutting it and now I use a dab of Estrace.

However. This is just one study. There are other (older) studies that do not show much systemic change and what they show is typically still within normal menopausal ranges. I don't have those normal ranges at the tip of my fingers so cannot say if this studies "5-fold increase" took the levels above normal menopausal ranges.

Plus, I'm assuming that the dose used (1g of Premarin cream) is much larger than my dab - an applicator-ful I'd guess.

So I'm hedging, on my personal decision. I wish they'd do some large studies on menopausal breast cancer survivors. Since the majority are on hormone therapy, I'd like to see these results of serum levels for those on Tamoxifen, and especially on AI's. But the only thing that will really tell the tale is to do long term recurrence and survival studies. And that won't be in time to help us figure out the best thing for us, today.

Debbie Laxague

Dr. Love Recommends Only Using The Smallest Amount Of Vaginal Estrogen Cream To Combat Vaginal Atrophy And Assoc. Symptoms, Which May Have A Lot Less Serum Estrogen Level Impact.

As a Premarin cream user (down to 0.5g every other Wednesday), I want to comment that we don't know the vaginal atrophic state of the women in the study. If they started out fully atrophic, then their vaginal vault had no mature cells in the lining to prevent any absorption of estrogens into the bloodstream. Also, they were using the cream everyday at 1g (1g - 1.5g is the usual dose to be given daily via package directions. After relief, one should scale back to the smallest effective dose). So, they are measuring the estrogen uptake during the absolute worst time ever_ during true therapy to replenish local estrogen levels in order to get maturation of immature vaginal epithelial cells. Not a good study at all. Good only in that we know that even Estring causes a temporary rise in systemic estrogen for the same reason and then it scales back.

I have had my prior to use level taken and then my onc didn't want to remeasure until after 6 wks on Estring (started with this product) and my level was the same. At 9 months, I switched to the small dose of Premarin once a week to "maintain" and I eventually moved to the once every other week and I am fine. I don't worry about this issue at all due to a healthy vagina protecting me as well as such a reduced use.

Becky,

I agree with you - this does not seem to be a very well designed study. Also, the amounts of these preparations the participants used, plus the frequency of use, are not at all what bc patients are advised to do, so the applicability to our demographic is not a one-to-one correspondence.

My surgeon and gyn are very supportive of my use of Estrace under their supervision and as they direct, which is very similar to your usage. My rads onc would prefer I use e-string, but is not against local estrogen therapy in general.

Some parts of the body require some estrogen to function, and they are parts I, for one, want in good working order!

Hopeful

One more opinion
 

Having used the Estring for several years as a Stage I, and then dropping off it for various reasons, I agree with Hopeful and Becky that even though it is in some ways less convenient to use Estrace than the Estring, using Estrace does let one adjust the dose to fit the need better. I'm back on the Estring at present, but planning to get a prescription for Estrace. Also, I did find that the Estring ring itself ended up being somewhat uncomfortable for intercourse at times (it seemed to pull on the tissues sometimes with movements).

AlaskaAngel

Thanks Debbie, I actually thought of that after I posted, LOL. I must also clarify that on my recurrence we found I came back as ER negative, so we don't think I am in too much danger from a mild amount of systemic effect. That said, I also haven't been using it very regularly at all for about 6 months, mostly out of laziness.

CAn I just overshare and add my two cents....Becky did you say vaginal vault?lol. Okay - I'll admit I am immature when it comes to discussing the hoo-hoo and hee-hee areas. However-I did start on the vagina pill (vagifem) and had very happy results (the vault was easily unlocked) but had BAD BAD migraine (not tonight dear...I have a headache) headaches. So the onc had me switch to estrace cream - gave me the "little dab'il'do'ya" directions. Like Brenda I was LAZY about the dabbing and lo and behold I have another freakin' UTI. So I am on Keflex - like I need another drug in my life. But I still am reluctant to use the cream - not because of fear of cancer but because I can't seem to use any amount of hormones without getting hot flashes and headaches. I can deal with the flashing - I cannot deal with the headaches - they are big and bad. Please post any ideas for me. I am frustrated but want a working vault (well oiled). I also use replens et al.

Well, I am joining the club. There was some bleeding when I had a pap smear last Friday, so the doctor (a physician's assistant) gave me a prescription for Premarin. She said to apply a very small amount to the outer and the opening area 3 times weekly as needed. I saw her the beginning of last week because of UTI. And she found out I was overdue for the exam.

I remembered there were discussions about the subject. So I did a search by keyword. Just wanted to thank everyone who has been contributing to this board. It made a world of difference. (And special thanks to Joe, Christine, and our sponsors.)

Jackie,
Premarin cream contains horse estrogens which include estrone (E1), one of the estrogens that stimulate breast tissue. Estrace and some others contain estradiol (E2), which can also stimulate tumor growth. Estriol (E3) is available from compounding pharmacies as a 0.5% vaginal cream. It is HIGHLY effective for vaginal atrophy and dryness, and does NOT stimulate breast tissue in vivo or in vitro. (It also probably does not help bone density or blood lipids as the other estrogens can). But for BC patients and survivors, it is MUCH safer than estrone or estradiol. Why isn't it promoted? It isn't availabe as a patented drug so no drug company profit motives. Most physicians do not distinguish one "estrogen" from another, including those identical to the ones our ovaries make versus those that are synthetic and chemically just slightly different, which allows them to be patented as drugs.

Uh, oh - am I going to turn into a horse now? :)

Thanks for the cautioning. I've applied it just once so far. Will do some more research before continuing.

Since I am taking Tamoxifen, I wonder if the cancer drug has enough power to ward off any possible estrogen effect brought on by either the pills or cream for vaginal atrophy.

Certainly we don't want (or need) to take a chance to increase the probability of recurrence. Thanks again.