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ESTROGEN

Older Women on Estrogen at Increased Risk for Needing Gall Bladder or Appendix Removed

TORONTO, ON -- May 16, 2000 -- Women over the age of 65 who are prescribed estrogen are more likely to have gallbladder or appendix removal surgery. This finding is from a study led by Dr. Muhammad Mamdani, Associate Scientist with the Institute for Clinical Evaluative Sciences (ICES) and Assistant Professor in the Faculty of Pharmacy, University of Toronto.

The study, published in the May 16th issue of the Canadian Medical Association Journal (CMAJ), tracked approximately 800,000 Ontario women over a five year period. Women on estrogen replacement were compared to control groups of women on other medications for the unrelated conditions of heart and thyroid disease.

The women on estrogen replacement were almost twice as likely to have had their gallbladders removed than were the other groups of women. The same increased rate of risk was noted for appendix removal.

"There still continues to be controversy about the benefits and risks of estrogen use in postmenopausal women. Our study is consistent with recent findings about the risks of this therapy that have gone largely unrecognized to this point," says Dr. Mamdani. Other recent studies have demonstrated a relationship between estrogen replacement therapy and abdominal pain, osteoarthritis and asthma. "The increased rate of gallbladder and appendix removal can be viewed as a marker for the less well-known physiologic effects of estrogen."

"The literature has shown that women who take estrogen replacement therapy tend to be healthier than those that don't, however this study points out that estrogen therapy may contribute to conditions associated with systemic inflammation or pain," says Dr. Mamdani.

ICES is a non-profit health services research organization dedicated to conducting research that contributes to the equity, effectiveness, quality and efficiency of health care in the province of Ontario.

The following study showing that women who smoke are not likely to show improvements in stopping osteoporosis may offer supportive evidence that estrogen increases the body accumulation of cadmium from tobacco smoke and that this cadmium interferes with bone growth, possibly by competing with copper.

Smoking, Low Body Weight, Risk Factors for Poor HRT Response

A DGReview of :"Identification of Early Postmenopausal Women with No Bone Response to HRT: Results of a Five-Year Clinical Trial"
Osteoporosis International

04/07/2000
By Mark Greener


Women who smoke and those with low body weights are more likely than other women to show poor skeletal responses to HRT, a new study shows. However, certain biochemical measurements may help clinicians predict which women are likely to be poor responders.

The study examined 74 women treated with sequential 2 mg oestradiol valerate and 1 mg cyproterone acetate during their early postmenopausal period and 104 who took placebo. The authors defined a non-responder as a woman whose change in bone mineral density (BMD) over the five-year study was similar to or worse than that seen among placebo users.

Based on this definition, 11 per cent of HRT users had not improvement in their spine BMD. Moreover, 26 per cent showed no response at their femoral neck. Smoking and low body weight emerged as statistically significant risk factors predicting non-response.

After six months, HRT users who did not show a response at their hip expressed higher mean serum levels of follicle stimulating hormone (FSH) and a less marked rise in serum oestradiol levels compared to responders. Women who did not respond at their spine expressed lower mean changes in serum FSH and alkaline phosphatase levels than did responders.

The authors conclude, firstly, that smokers and women with low body weight are more likely to show a poor response to HRT at their hip and spine and, secondly, that measuring serum FSH, oestradiol and alkaline phosphatase levels during the first few months of treatment may help identify non-responders.

Hormone therapy raises thromboembolism risk for some women

05/04/2000
By Anne MacLennan

Postmenopausal therapy with estrogen plus progestin puts women with coronary heart disease at increased risk for venous thromboembolism, a multi-centre study has found.

Authors of the study underline the need for doctors to be alert to this new finding when considering risks and benefits of hormone therapy for postmenopausal patients.

Conducted at 20 clinical centres in the United States, the study included 2,763 postmenopausal women whose average age was 67 years. (All were younger than 80 years.) All of the women had coronary heart disease but no previous venous thromboembolism (VTE). None had had a hysterectomy.

Over an average of 4.1 years follow-up, 34 of the women in the hormone therapy group and 13 on placebo had VTE events.

Analysis showed risk of VTE was increased in women with lower-extremity fractures or cancer and for 90 days after in-patient surgery or non-surgical hospitalization. Risk decreased with aspirin or statin use.

The group on hormone therapy -- 1,380 women -- received 0.625 mg conjugated equine estrogens plus 2.5 mg medroxyprogesterone acetate, in one-tablet form. The other 1,383 women received look-alike placebo.

Outcome measures were documented deep venous thrombosis or pulmonary embolism.

Although oral contraceptive use is known to increase risk for VTE, this is one of few reports to date to document the effect of hormone therapy in women who are postmenopausal.


Annals of Internal Medicine, 2 May 2000.132:689-696.


I'm not very sure what the following study is about but was intrigued by the use of 125I-radioiodinated estrogens.  What this suggests to me is that iodine is a part of the estrogen molecule or becomes attached to it.  If this weren't true, then 125I couldn't be used as a radiotracer.  Because of the importance of iodine in the thyroid, I find this very interesting and will try to find out more about the iodine-estrogen connection.

 

 
Steroids 2000 Feb;65(2):74-84

(17alpha,20E/Z)-iodovinyl- and 16alpha-iodP618-homoestradiol derivatives: synthesis and evaluation for estrogen receptor imaging.

Ali H, Rousseau J, Lafreniere J, van Lier JE

Department of Nuclear Medicine and Radiobiology, Faculty of Medicine, Universite de Sherbrooke, Quebec, Canada.

Three new 125I-radioiodinated estrogens featuring a 13beta-ethyl instead of the natural 13beta-methyl group, i.e. 18-homoestradiols, were synthesized and evaluated as potential estrogen receptor imaging agents. The 16alpha-iodo-18-methylestradiol and the 125I-labeled analog were synthesized from the corresponding 16beta-bromo analog by the halogen-exchange method. The cis-bromohydrin precursor was obtained by bromination of an estrone enolacetate, followed by epimerization and reduction. The isomeric (17alpha,20E/Z)-iodovinyl-18-methylestradiols were prepared via the vinyltin intermediates. Treatment of 18-methyl-17alpha-ethynylestradiol with tri-n-butyltin hydride, in the presence of azobisisobutyronitrile as catalyst and heating at 90-100 degrees C afforded the (17alpha,20E)-tri-n-butylstannyl isomer as the major product. Changing the catalyst for triethyl borane, at room temperature, mainly gave the 20Z-isomer. The nca 125I-labeled analogs were obtained from their corresponding tin intermediates upon treatment with [125I]NaI in the presence of H2O2. The 16alpha-[125I]iodo- and isomeric (17alpha,20E/Z)-[125I]iodovinyl-18-methylestradiols were evaluated for estrogen receptor-mediated uterine uptake in immature female rats. Homologation of the C13-methyl group did improve the uterine uptake of the iodovinyl derivatives, but also increased blood retention, resulting in lower target uptake ratios. In the case of the 16alpha-iodo analog uterine retention decreased upon C13-homologation.

The following study suggests the existence of a copper-tin compound with is involved in estrogen metabolism.

Steroids 1994 Oct;59(10):590-6

Synthesis and radiochemistry of 2,4-disubstituted 17 alpha-iodovinylestradiols.

Cummins CH

Organic Chemicals and Polymers Laboratory, Central Research and Development, Dow Chemical Company, Midland, MI 48674.

This report details the preparation of three compounds which are structurally designed to have depressed metabolism and/or conjugation: 2,4-dibromo-, 2,4-dichloro-, and 2,4-dimethyl-17 alpha-iodovinylestradiol. Their synthesis includes the use of two novel transformations based upon tin chemistry: preparation of an intermediate 17 alpha-vinylstannanes via stannylcupration of a 17 alpha-ethynyl steroid, and preparation of the 2,4-dimethyl functionality via a palladium catalyzed coupling of 2,4-dibromoestrone acetate with tetramethyltin. The preparative radiochemistry of these three materials is also described.
From Dr. Mercola's site, www.mercola.com:

Premarin and Estrogens Decrease Thyroid Hormone in Women

Older women who are on both estrogen replacement and thyroid replacement therapy may need a boost to the thyroid portion of their regimen, new research suggests. Increased estrogen, according to one investigator, can lower thyroid levels in some women being treated for already-low concentrations of the hormone.

To be safe, women taking thyroid hormones should receive check-ups within a few months of starting estrogen replacement.

The study was funded by Knoll Pharmaceutical, which manufactures Synthroid™.

Thyroid hormone is used to treat hypothyroidism, a condition in which the body's levels of the hormone are too low. The thyroid gland acts like a barometer--churning out, as needed, hormones that help regulate a range of vital functions including

  • heart rate
  • blood pressure
  • body temperature
  • metabolism

An underactive or non-functioning gland produces little or no thyroid hormone, triggering symptoms such as

  • sluggishness
  • chills
  • constipation
  • weight gain

Increases in estrogen, such as those that occur in pregnancy, lead to dips in thyroid levels. Among women with normal thyroid function, the gland can compensate and produce more thyroid hormone. But this barometer does not work in women with hypothyroidism.

The author recommends that women receiving both types of hormone replacement have their thyroid levels checked within 12 weeks of starting on estrogen--particularly women who are on thyroid hormone as part of thyroid cancer treatment.

The New England Journal of Medicine June 7, 2001; 344: 1743-1749, 1784-1785

DR. MERCOLA'S COMMENT:

Several issues are relevant here.

First off, traditional medicine has some serious issues with their understanding of thyroid glandular replacements. Their reliance on synthetic alternatives has caused unnecessary incredible grief and suffering for millions of women.

So, even if the levels were monitored properly as suggested, most women would be given higher doses of an inferior hormone. Please note that the makers of Synthroid funded this article. They are currently in a heap of trouble as Synthroid may be pulled from the market in August.

Secondly, most postmenopausal women do NOT need estrogen. In my view the only women who should be placed on estrogen are those who have their ovaries removed. If a woman still has functioning ovaries her body has the potential to produce estrogen in sufficient quantities if other factors are normalized.

JAMA published a landmark article this week on this topic and I will post it next week.

As I said last year, if you still believe that estrogen is good for you, you have been brain washed by the traditional media. I would encourage you to review Dr. John Lee's excellent books on the topic. What Your Doctor May Not Tell You About Premenopause : Balance Your Hormones and Your Life from Thirty to Fifty

These companies will use every trick in the book to get women to take these drugs which actually cause cancer. They tried to say that estrogen reduced Alzheimer's, but a few years later the results showed that it does not. The long held notion that estrogen reduces heart disease is just plain untrue.

One of the classic arguments that traditional medicine offers to convince women to begin or stay on estrogen therapy is osteoporosis prevention, heart disease prevention, and more recently the hope of prevention of Alzheimer's.

With 4 huge studies already showing no benefit, this avenue does not seem promising, at least with the synthetic progestin and horse-derived estrogen used. Maybe a more appropriate regimen of natural hormone replacement would show better results.

From Dr. Mercola at mercola.com (March 2, 2002):

Hormone Replacement Therapy Linked to Breast Cancer

Adding to evidence that hormone replacement therapy (HRT) can potentially raise a woman's risk of breast cancer, a new US study links recent, long-term HRT with a heightened risk of the disease.

Researchers found that HRT with estrogen alone or estrogen-plus-progestin was associated with a 70% increase in breast cancer risk when the therapy was taken for 5 years within the 6 years preceding the cancer diagnosis.

The findings build on previous research showing a link between long-term HRT and breast cancer and help clear up the question of whether combination HRT and estrogen-only HRT carry similar risks.

In addition, the study of about 1,300 women found that HRT use had a particular link to lobular breast cancer, the form of the disease that begins in the breast's lobules. It is far less common than ductal breast cancer, which begins in the milk ducts.

Women who were recent, long-time users of HRT faced a three-fold risk of lobular cancer compared with women who never used HRT.

These women also had about a 50% increase in the risk of ductal cancer.

JAMA February 13, 2002;287:734-741

DR. MERCOLA'S COMMENT:

After all these years of estrogen hype it is becoming more and more clear to traditional medicine that the benefits of estrogen don't outweigh the risks.

Estrogen has long been proven to not help with heart disease nor prevent Alzheimer's.

So that leaves us with osteoporosis and hot flash relief.

It has been my experience that black cohosh works far more effectively for hot flash relief.

So that leaves us with osteoporosis. Well, a study published less than a year ago in JAMA showed that estrogen was not helpful to prevent against hip fractures.

Fortunately one can take vitamin D, K, omega three fats and plenty of vegetables and exercise to address osteoporosis.

One can only logically conclude that there is no reason for a woman to take hormone replacement therapy, unless her ovaries have been removed or she is interested in getting breast cancer.

It is important to make a distinction between women who have had their ovaries removed and those that have not. Those that have will likely benefit from low dose natural human estrogen replacement while those who still have ovaries will likely not.