Hormone Replacement Gets New Scrutiny Finding of Increased Risks Prompts Federal Effort By Marc KaufmanWashington Post Staff WriterWednesday, August 14, 2002; Page A01

Federal officials announced yesterday that they have begun a major reassessment of the risks and benefits of all combination hormone products containing estrogen used by post-menopausal women, one month after a large government study found potentially serious side effects from hormone replacement therapy.

The federal effort could change how popular drugs such as Prempro are advertised, prescribed and used, with new recommendations about who should take them, at what dosages and for how long.

The initiative, which will include several public forums this fall sponsored by the National Institutes of Health, the Food and Drug Administration and the Agency for Healthcare Research and Quality, will also try to guide future research on the suddenly more complex and controversial subject.

The move marks the first significant action by the federal government in response to the latest findings about hormone therapy. It is designed to address the widespread confusion that has caused anxious women to inundate doctors with questions about whether they should continue taking the powerful hormones.

"Somebody needed to take a leadership role, because there is chaos in the medical societies," said Wulf H. Utian, executive director of the North American Menopause Society, who has been invited to participate in the meetings. "It's time to clear the air and address the issues."

The brief announcement of the initiative came as the FDA separately pushed for immediate changes in the label and the package insert for the hormone combination sold as Prempro to reflect the risks confirmed by the Women's Health Initiative (WHI).

Part of that federally funded study was stopped three years early because of small but statistically significant increases in heart disease, breast cancer, stroke and blood clots among women taking Prempro, a combined estrogen-progestin drug. While the study used only Prempro, agency officials said they have new questions about other estrogen-progestin products on the market, as well.

In response to the immediate FDA concerns, officials at Wyeth Pharmaceuticals, maker of Prempro, said the company expects to submit new safety precaution information as early as this week that will take into account the WHI findings. The WHI study was testing the widely held hypothesis that hormone therapy reduced the risk for heart disease in particular and, so, was especially surprising.

"The FDA says it is our responsibility to get new information out there, and we agree," said Bruce Burlington, Wyeth's vice president for regulatory compliance. He said that many of the WHI findings on increased risks to women were already known and incorporated into the Prempro label but that "the risks were better quantified in WHI."

These initial steps can be taken without formal FDA approval. But officials said that they are aggressively reviewing hormone replacement therapy generally -- now used by 14 million menopausal and post-menopausal American women -- and that more wide-ranging changes can be expected.

As part of the effort, federal officials want to explore whether hormone therapies and their producers have encouraged women to believe menopause is a condition to be treated, rather than an inevitable and natural set of changes to be managed. The hormone therapy issue is being actively debated within medical societies, too, with the American College of Obstetricians and Gynecologists, the North American Menopause Society and others forming task forces on hormone replacement in response to the WHI findings.

Reflecting the FDA's discomfort with the way that hormone treatments have been widely presented as an antidote to menopause, the agency has told Wyeth to remove all references to "hormone replacement therapy" from its Prempro label. The "replacement" model, officials said, has never been accepted by the agency, which approved Prempro for specific symptoms of menopause and to prevent osteoporosis, a reduction in bone mass.

"The impact of the WHI findings [is] very far-reaching, and that fact is not lost on the FDA," said Florence Houn, a director at the FDA's Center for Drug Evaluation and Research. "As a public health agency, we need to step to the plate and reassess the risk-benefit conditions for labeling and risk management for patients."

Estrogen products have been used for decades and have helped millions of women handle the sometimes-severe symptoms of menopause, including hot flashes, night sweats, sexual discomfort and the increased risk of bone fractures.

For years, studies on heart disease, Alzheimer's, colon cancer and bone fractures also showed potential benefits to women taking hormone replacement long-term, and those findings were widely embraced by doctors and advertised by the drugmakers. The earlier positive findings on estrogen and heart disease, for instance, were considered strong enough by the American Heart Association to be included in its literature for women as recently as 1997.

But studies in the past several years began to raise doubts about the benefits and risks from long-term hormone therapy, and the large WHI study concluded that hormone therapy actually increased the risk of heart disease. That finding has required a quick pivot by medical authorities, individual doctors and, now, federal officials.

Further complicating the picture, the WHI study found that hormone therapy did help protect women against colon cancer and hip fractures. In addition, another arm of the WHI study did not find cardiovascular and cancer dangers with estrogen treatment alone (as opposed to the estrogen-progestin combination) when it was used by women who have had hysterectomies. That part of the study was allowed to continue.

The FDA expects to hold an expert advisory meeting this fall or winter to make recommendations about how hormone therapies should be used. Among the issues to be addressed are whether hormone treatment should be limited to several years, whether all hormone combinations containing estrogen carry the same risks, and whether estrogen-combination products require the kind of more prominent black box warnings that are used for drugs with potentially fatal side effects.

Although the WHI study did not find an increase in deaths from breast cancer, heart disease or stroke before it was stopped, the study did conclude that Prempro was associated with a greater risk of those diseases.

"Ultimately, the label that does get full FDA approval may well look quite different from what the company feels is needed for immediate strengthening," Houn said.

The FDA-approved label for a drug is key to how it is advertised, prescribed and used by patients. While doctors can write prescriptions off-label, companies can advertise to consumers and doctors only the uses approved by the FDA, and they must convey the side effects deemed serious by the agency.

Wyeth officials said that since the WHI study was discontinued, they have stopped direct-to-consumer advertising about hormone replacement but increased visits to doctors to explain the results.

© 2002 The Washington Post Companyhttp://www.washingtonpost.com/wp-dyn/artic...-2002Aug13.html

Mary ,<br> &nbsp; &nbsp; This piece was interesting since I was wondering<br>today why I haven't seen any recent ads with<br>celebrites hawking HRT. &nbsp;I remember the ads<br>stating to &quot;ask your doctor.&quot; &nbsp;I also know that the<br>first HRT I was given by my doctor was a sample of<br>Prempro, along with a prescription for the same.

I was surprised by this statement: total prescriptions of the entire Premarin franchise are down about 13% to 15%, while total prescriptions of Prempro are down 38% to 40%.  I thought it would be much more.  Guess those other women don't come to Power Surge!

Wyeth Doesn't Know Effect Of Hormone Therapy Sales Drop Thursday September 19, 1:13 pm ET

By Hollister H. Hovey, Of DOW JONES NEWSWIRES

NEW YORK -(Dow Jones)- Wyeth hasn't fully quantified the effect declining sales in its hormone replacement therapy franchise will have on its bottom line, an executive said Thursday.Speaking at the Bear Stearns Healthcare Conference in New York, Jack O'Connor, vice president and treasurer, declined to give any financial guidance for the company.

A recent study into the company's combination progestin-estrogen drug Prempro was halted after some women showed an increased risk of breast cancer after taking the drug long-term. Sales of the entire franchise, which includes single hormone therapies, plummeted after the study results came out, but have since plateaued

As of the week ending Aug. 30, total prescriptions of the entire Premarin franchise are down about 13% to 15%, while total prescriptions of Prempro are down 38% to 40%.

The National Institutes of Health will hold a workshop on Oct. 23 and 24 to discuss the findings of the study, called the Women's Health Initiative. The U.S. Food and Drug Administration has announced plans for an advisory panel open forum meeting, but no date has been set. Justin Victoria, vice president of investor relations, said he'd guess that it will occur sometime in November.

Wyeth in late August changed the label on the drugs in the franchise to represent the data from the trial, but the company expects further label changes after the NIH and FDA meetings.

The company doesn't foresee massive litigation surrounding Prempro, since the findings weren't really new risks and the product wasn't withdrawn. Of 12 suits filed against the company, three have already been dismissed.

-By Hollister H. Hovey, Dow Jones Newswires; 201-938-5287;

<<"The FDA says it is our responsibility to get new information out there, and we agree," said Bruce Burlington, Wyeth's vice president for regulatory compliance.>>

ha ha ha ha ha ha. Oh, sure they agree! That's why they sent out more than 100,000 letters to doctors and other practitioner (as reported in the press) telling them to try to convice their patients to stay on HRT. They must think women are extremely stupid.

I asked our pharmacist if she had noticed a big drop in Prempro refills since the results of the study were published. She said that surprisingly many women had decided to stay on their HRT.  She said that their doctors had told them that the decision was up to them and they could continue the Prempro if they felt better on it.  I am not a fan of  the synthetic hormones. In fact, it angers me that the greedy drug companies put profits over the welfare of  the public.  But it appears that some women do feel better on synthetic hormones and are willing to take the risk rather than feel like they did before starting HRT.

Government Offers Hormone Caution

.c The Associated Press

WASHINGTON (AP) - Women should not use estrogen and progestin supplements in hopes of preventing bone loss or other chronic ailments, the government said Tuesday.

Federal scientists broke the news in July that long-term use of the combination hormone therapy significantly increased women's risk of breast cancer, heart attacks and strokes.

The news caused dismay and confusion for millions of American women. Many used the combination not just in hopes of long-term health but to relieve short-term menopausal symptoms such as hot flashes and night sweats, and wondered how long they could safely use hormones for that purpose.

Now the independent panel charged by the U.S. government to set the nation's disease-prevention guidelines has weighed in, with recommendations not likely to settle the confusion.

The clear risks of routine estrogen-and-progestin use outweigh the few long-term benefits, such as bone strength, the U.S. Preventive Services Task Force said Tuesday. But when it comes to menopause symptom relief, the panel urged women to discuss their personal disease risks with their health provider in choosing whether to try hormones.

For example, most discussion of hormone therapy's risks has centered on long-term use, yet the risk of heart attack actually rises in the first year women swallow the pills, said task force co-chairwoman Dr. Janet Allan. A woman with high cholesterol or high blood pressure might make a different decision on using hormones for hot flashes than a healthier woman would.

"This is tough for women," Allan acknowledged.

The task force last examined hormone therapy in 1996, calling the evidence too paltry to decide if women should use it. But doctors' and patients' enthusiasm for hormones overrode that cautionary note, and an estimated 6 million women were taking the estrogen-progestin combination when the National Institutes of Health announced the bad news in July.

Millions more are thought to be taking estrogen alone, something reserved for women who have had their uterus removed. The task force said there's not enough evidence to know yet if estrogen-only therapy is any safer than combination therapy; a study of that question is continuing.

  10/15/02 18:20 EDT

Copyright 2002 The Associated Press.

http://www.washingtonpost.com/wp-dyn/artic...Doubts Grow About Post-Menopausal Hormone Use At NIH Conference, Emerging Skepticism That Combination Therapy Should Be Used to Prevent Disease By David BrownWashington Post Staff WriterSunday, October 27, 2002; Page A12

Three months after the unexpected end of a huge study of postmenopausal hormone use, a consensus is emerging that there is essentially no use for the drugs in the prevention of chronic ailments that come with age.

Although the hormones have both good and bad effects -- raising the risk for heart attack, breast cancer and blood clots while lowering it for osteoporosis and colon cancer -- their net effect is harmful in terms of disease prevention. They still have a role in the treatment of symptoms of menopause. But how large a role is a matter of dispute.

Those were among the conclusions that emerged from a two-day meeting held this week at the National Institutes of Health. The gathering was called to assess the immediate consequences of the hormone study results and talk about what new research may be needed.

"For the community of practitioners, the clear message is: If you're using hormones, try to limit it to short-term treatment for symptoms. It's not a prescription for life -- and that's a big, big change," said Florence Comite, a physician and founder of the women's clinic at Yale University, and one of about 500 medical researchers, clinicians and regulatory officials who attended.

When the results from the Women's Health Initiative hormone trial were released in early July, Comite had more than 100 patients taking combinations of estrogen and progestin, the two hormones that were studied. About one-third have stopped. "I think the dust has settled to some degree," she said.

Ronald K. Ross, a preventive medicine physician at the University of Southern California said he believes there is less confusion in the scientific community about the study results than the public might think. "Combination treatment [for disease prevention] is certainly out of the question," he said, summing it up.

Agreement on the study's implications, however, is far from universal.

Some people at the NIH workshop argued that hormone preparations different from those used in the study might have given different results. Some believe that the long-imagined cardiovascular benefit would have been seen if younger women had been enrolled, and if they'd started taking hormones as soon as they entered menopause. Some people think lower doses of the medicines won't cause harm. There was much talk about "individualizing" therapy for each woman -- a concept that appears to leave much room for the liberal prescription of hormones for long-term use.

"Is there a role for hormone therapy in prevention? Absolutely," said Frederick Naftolin, an obstetrician-gynecologist who is also affiliated with Yale. "Preventing bone loss, preserving skin, possibly in dementia. And I'm still not convinced there is no role in [preventing] cardiovascular disease."

This view appeared to be a distinct minority. A number of experts -- and authority figures -- went out of their way to say it was also an incorrect interpretation of study's results.

"It is clear that this combination hormone therapy should not be generally used for prevention purposes of chronic diseases," NIH's director, Elias A. Zerhouni, said in a statement published at the end of the workshop. Asked if this means that prescribing estrogen and progestin to a woman without symptoms is bad practice, he said: "Yes, it is bad practice."

Marcia L. Stefanick, a physiologist at Stanford University and one of the chief architects of the study, said she believes there is a real hazard in trying to find exceptions to the main findings.

"To say that the risks don't exceed the benefits -- unless you are focusing on menopausal symptoms -- is simply wrong," she said.

In what is probably the closest to an official position on the issue, the United States Preventive Services Task Force -- which provides advice to the Department of Health and Human Services -- next month will publish a guideline that "recommends against" combination hormone use for the prevention of disease in women.

In the mid-1980s, about 40 percent of postmenopausal women in America took hormone replacements at least for a while. The fraction who do today is unknown, although it is in the millions.

The main reason estrogen and progestin combinations are prescribed is to relieve hot flashes and other symptoms of menopause. The Women's Health Initiative study didn't examine that use -- or the benefit gained from the medicines' near-certain ability to relieve those symptoms. Instead, it looked at the claims that hormones, taken for years or decades, prevent disease, heart disease in particular.

The study randomly assigned nearly 17,000 women to take either a placebo or an estrogen-and-progestin combination. The participants' average age was 63, meaning that most were more than a decade beyond menopause, which occurs on average at age 51 in the United States.

Although designed to last eight years, the study was stopped after a little more than five because it was clear that the major anticipated benefit -- fewer heart attacks in hormone takers -- wasn't occurring. In fact, there were more heart attacks in women assigned to the drugs.

(A study of about 11,000 women who have had a hysterectomy -- the surgical removal of the uterus -- is continuing. They are assigned to take estrogen alone or a placebo. None is taking progestin.)

In the entire group, the number of bad events was small, and the absolute risk for any individual woman very low.

For example, at the rates seen over the course of the study, hormone use will cause an extra heart attack each year in about 1 in every 1,100 women taking the medicines; an extra stroke in 1 in 1,200; an extra blood clot of a serious nature in 1 in 600; and an extra case of breast cancer in 1 in 1,300. At the same time, hormone use will protect 1 in about every 2,000 women from a hip fracture she would otherwise have suffered; and 1 in 1,700 from a case of colon cancer.

A calculation presented at the meeting by Deborah Grady, a physician and epidemiologist at the University of California in San Francisco, suggested that given those numbers, essentially nobody is likely to benefit from preventive use of hormones.

For example, if women with family histories of colon cancer (which doubles their own risk) take hormones, the net effect still tips toward harm, with 1 in 700 users suffering an additional one of the bad events. For women with osteoporosis, it's 1 in 650. Only in women with osteoporosis who have already suffered a fracture do the risks and benefits balance out, according to Grady's calculation. But for them, she argued, there are many lower-risk interventions, such as exercise, smoking cessation, calcium and vitamin D supplements, and the anti-osteoporosis drugs called bisphosphonates.

Further analysis of the data is underway. But the investigators said the main trends were seen in all age groups and races, and that no subpopulations appear to benefit.

For example, for cardiovascular events (heart attack, stroke, clots) the risk was increased 67 percent in the youngest group of hormone users, those age 50 to 59 at the start of the study. For women 60 to 69, it was up 26 percent, and for the oldest women, those 70 to 79, it was up 18 percent. Breast cancer risk was up 23 percent, 22 percent and 42 percent, respectively, in those three age groups.

The potential wild card in hormone use is dementia.

Studies have shown that women with Alzheimer's disease are less likely to have taken hormones than women without Alzheimer's. That observation, however, doesn't mean hormones protected them. Only a randomized, controlled trial could determine that.

A subgroup of elderly women in the Women's Health Initiative study is being observed for the development of dementia. There is also a trial of two estrogenlike compounds (tamoxifen and raloxifene) underway.

A recent trial of estrogen in women who already have Alzheimer's found the hormone didn't help. However, if it turned out there was a preventive effect, that benefit might swamp the harms.

For example, out of 10,000 women who are older than 65 and have a close relative with Alzheimer's, 500 every year will develop dementia. That's far, far more than the 20 additional bad events per 10,000 women per year seen in the hormone users in the Women's Health Initiative study.

© 2002 The Washington Post Company

Well, I just went through Lasik for the second time yesterday, the first was in Feb of this year. I started Estratest in the fall of '96 and my astigmatism got so bad over the next 5 years, I couldn't wear my contacts anymore. I stopped the Estratest in May of this year and my newly preformed Lasik that had been very good at correcting my vision started to fail and my distance which had been corrected nicely wasn't so good anymore. Could there be a correlation between my former HRT and my vision problems? My pharmacist says absolutely, that any hormone/steroid that you take can cause changes in eyesight and the "steepening of the cornea". This is not a publicized side effect of HRT. I probably could have skipped the Lasik had I come off of the Estratest sooner.

Hiya, CSIM - welcome to PowerSurge.  That's not a particularly publicized side effect of HRT, but it's definitely listed in some of the paperwork that they give with the prescriptions.  I took Estrace (and Provera) for a while and I was very concerned that i might not be able to wear my contacts anymore.  That didn't happen to me, but I went off the HRT anyway.

Here's a copy of the prescribing info for Estratest H.S.  hidden near the end is this side effect... · intolerance to contact lenses;

esterified estrogens and methyltestosterone   Pronunciation: ess TARE uh fied ESS troe jenz and meth ill tess TOSS ter ownBrand: Estratest, Estratest H.S., Menogen, Menogen HS

What is the most important information I should know about esterified estrogens and methyltestosterone? •  Esterified estrogens increase the risk of developing a condition (endometrial hyperplasia) that may lead to cancer of the lining of the uterus. Taking progestins, another hormone drug, with esterified estrogens lowers the risk of developing this condition. Therefore, if your uterus has not been removed, your doctor may prescribe a progestin for you to take together with the estrogen. Visit your doctor regularly and report any unusual vaginal bleeding right away.   •  Have yearly physical exams and examine your breasts for lumps on a monthly basis. •  Notify your doctor if you experience vomiting, swelling of your arms or legs, hoarseness, deepening of your voice, male-pattern baldness, excessive hair growth, clitoral enlargement, or yellowing of your skin or eyes. •  Do not take esterified estrogens and methyltestosterone if you are pregnant.

What is esterified estrogens and methyltestosterone? •  Esterified estrogens are female sex hormones necessary for many processes in the body. •  Methyltestosterone is a naturally occurring androgen ("male" sex hormone) that is produced in the testes in men and, in small amounts, by the ovaries and the brain in women. •  The combination, esterified estrogens and methyltestosterone, is used to treat symptoms of menopause that have not responded to estrogen therapy alone. Most often, esterified estrogens and methyltestosterone is used to treat the symptoms of menopause in women who also have diminished libido (a declining interest in sexual activity). •  Esterified estrogens and methyltestosterone may also be used for purposes other than those listed in this medication guide.

Who should not take esterified estrogens and methyltestosterone? •  Do not take esterified estrogens and methyltestosterone without first talking to your doctor if you have      · a circulation, bleeding, or blood-clotting disorder;      · undiagnosed, abnormal vaginal bleeding; or      · any type of breast, uterine, or hormone-dependent cancer. •  Taking esterified estrogens and methyltestosterone may be dangerous in some cases if you have any of the conditions listed above. •  Before taking esterified estrogens and methyltestosterone, tell your doctor if you have      · high blood pressure, angina, or heart disease;      · high levels of cholesterol or triglycerides in your blood;      · liver disease;      · kidney disease;      · asthma;      · epilepsy;      · migraines;      · diabetes;      · depression;      · gallbladder disease;      · uterine fibroids; or      · had a hysterectomy (uterus removed). •  You may not be able to take esterified estrogens and methyltestosterone, or you may require a dosage adjustment or special monitoring during treatment if you have any of the conditions listed above. •  Esterified estrogens and methyltestosterone are in the FDA pregnancy category X. This means that esterified estrogens and methyltestosterone will cause birth defects in an unborn baby. Do not take this medication if you are pregnant or are planning a pregnancy. •  Esterified estrogens may pass into breast milk, decrease milk flow, and have other effects on milk composition. It is not known whether methyltestosterone will affect a nursing baby. Do not take esterified estrogens and methyltestosterone without first talking to your doctor if you are breast-feeding a baby.

How should I take esterified estrogens and methyltestosterone? •  Take this medication exactly as directed by your doctor. If you do not understand these directions, ask your pharmacist, nurse, or doctor to explain them to you. •  Take each dose with a full glass of water. •  Take esterified estrogens and methyltestosterone with food or milk if you find it causes stomach upset. •  Try to take this medication at the same time each day. You may be taking it every day, or every day for 3 weeks with 1 week off each month to mimic your body's natural cycle. Follow the directions on your prescription label. •  Have yearly physical exams and examine your breasts for lumps on a monthly basis. •  Store esterified estrogens and methyltestosterone at room temperature away from moisture and heat.

What happens if I miss a dose? •  Take the missed dose as soon as you remember. If it is almost time for your next dose, skip the dose you missed and take only your next regularly scheduled dose as directed. Do not take a double dose of this medication unless otherwise directed by your doctor.

What happens if I overdose? •  An overdose of this medication is unlikely to threaten life. Consult an emergency room or poison control center for advice. •  Symptoms of an overdose might include nausea, vomiting, and breakthrough bleeding.

What should I avoid while taking esterified estrogens and methyltestosterone? •  There are no restrictions on food, beverages, or activity while taking esterified estrogens and methyltestosterone unless your doctor directs otherwise.

What are the possible side effects of esterified estrogens and methyltestosterone? •  If you experience any of the following serious side effects, stop taking esterified estrogens and methyltestosterone and seek emergency medical attention or notify your doctor immediately:      · an allergic reaction (difficulty breathing; closing of your throat; swelling of your lips, tongue, or face; or hives);      · a blood clot (pain, redness, and swelling in an arm or leg; shortness of breath; chest pain; headache; blurred vision; or confusion);      · a lump in a breast;      · liver damage (yellowing of the skin or eyes, nausea, abdominal pain or discomfort, unusual bleeding or bruising, severe fatigue);      · vomiting; or      · hoarseness, deepening of your voice, male-pattern baldness, excessive hair growth, or clitoral enlargement (these changes may be irreversible).

•  Other, less serious side effects may be more likely to occur. Continue to take your medication and talk to your doctor if you experience      · decreased appetite or nausea;      · swollen breasts;      · acne or skin color changes;      · increased or decreased sex drive;      · migraine headaches or dizziness;      · water retention (swollen hands, feet, or ankles);      · intolerance to contact lenses;      · depression; or      · changes in your menstrual cycle or breakthrough bleeding. •  Esterified estrogens increase the risk of developing a condition (endometrial hyperplasia) that may lead to cancer of the lining of the uterus. Taking progestins, another hormone drug, with esterified estrogens lowers the risk of developing this condition. Therefore, if your uterus has not been removed, your doctor may prescribe a progestin for you to take together with the estrogen. Visit your doctor regularly and report any unusual vaginal bleeding right away.   •  It is unclear to what extent estrogen treatments may affect the risk of breast cancer. •  Side effects other than those listed here may also occur. Talk to your doctor about any side effect that seems unusual or that is especially bothersome.

What other drugs will affect esterified estrogens and methyltestosterone? •  Before taking esterified estrogens and methyltestosterone, tell your doctor if you are taking any of the following medicines:      · an anticoagulant (blood thinner) such as warfarin (Coumadin);      · a thyroid medication;      · insulin or another diabetes medicine such as glipizide (Glucotrol) or glyburide (Diabeta, Micronase);      · tamoxifen (Nolvadex);      · a tricyclic antidepressant such as amitriptyline (Elavil), doxepin (Sinequan), nortriptyline (Pamelor), imipramine (Tofranil), and others;      · didanosine (Videx);      · phenytoin (Dilantin) or ethotoin (Peganone);      · carbamazepine (Tegretol);      · phenobarbital (Solfoton, Luminal);      · primidone (Mysoline); or      · rifampin (Rifadin). •  A dosage adjustment or special monitoring may be required during treatment if you are taking any of the medicines listed above. •  Drugs other than those listed here may also interact with esterified estrogens and methyltestosterone. Talk to your doctor and pharmacist before taking any prescription or over-the-counter medicines.

Where can I get more information? •  Your pharmacist has additional information about esterified estrogens and methyltestosterone written for health professionals that you may read.  

--------------------------------------------------------------------------------Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

The information in this leaflet is not intended to cover all possible uses, directions, precautions, drug interactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse, or pharmacist. © Multum Information Services 2000. Version: 2.01. Revision date: 3/23/00.  

~~~~~~~~~~~~~Best of luck to you - keep us posted how you're doing

Did you hear that they are continuing the studies with the combined preparation on the effects on Alshiemer's and Osteoarithis?  (I know, I can't spell worth beans!)

Zelma

More bad news...

http://www.reuters.com/newsArticle.jhtml?t...storyID=1889596

Estrogen, UV Added to US Govt. List of Carcinogens Wed December 11, 2002 11:05 AM ET By Todd Zwillich

WASHINGTON (Reuters Health) - A new US government report has for the first time identified estrogen-containing drugs and ultraviolet light as cancer-causing agents, federal agencies announced Wednesday.

The report also lists wood dust, common in carpentry shops and saw mills, as a known cause of lung cancer. Fifteen other compounds, including industrial chemicals, dyes and one compound found in foods cooked at high temperatures, were also added to the list as probable human carcinogens.

The report, published every 2 years by the National Toxicology Program, contains little new information about the agents it lists. Instead, it is a collection of known experimental data that the government uses to keep a running catalog of cancer-causing agents.

Federal agencies and Congress use the list to guide regulations and legislation governing industrial and environmental health hazards.

Wednesday's additions expanded the list to 228 compounds either "known" or "reasonably anticipated" to cause cancer in humans. It does not make conclusions about the magnitude of cancer risk posed by any of the compounds or what types of people may be most vulnerable.

Steroidal estrogens were added to the list for the first time because of research data linking the compounds to an increased risk of cancer of the endometrium, or lining of the uterus. They have also been associated with a rise in breast cancer risk.

Steroidal estrogens are used in hormone replacement therapy for menopausal women, and physicians are supposed to weigh the risk of cancer against the benefits of the drugs.

Estrogen replacement therapy is also known to reduce the chances of ovarian cancer in women who take it.

Broad-spectrum ultraviolet light, found in natural sunlight and in light used in tanning beds, was also classified as a known carcinogen because of a strong connection with cancers of the skin, lips and eyes, according to the report.

The report also upgraded beryllium compounds, which are commonly used in ceramics shops, nuclear reactors and jewelry making, from a probable to a known carcinogen.

Can someone please tell me what "steroidal" estrogen is?  Is it the Vivelle Dot of estradoil I'm on?  I'm starting to panic...

Abigail, I'd never heard this particular term, but when I looked it up, I got this info. The Vivelle Dot is a non-steroidal estrogen, but it's still estrogen.

Welcome to Power Surge border=0 alt=smile.gif />

Medical Crossfire Vol. 3 No. 4, April 2001 A scientific advisory panel of the National Toxicology Program Board of Scientific Counselors recently recommended that steroidal estrogens be added to a list of agents known to be a cause of cancer.(1) Although there was no suggestion by the panel that medical use of estrogen be restricted, the panel’s vote of eight to one has sparked a debate in the medical community. To gain further insight into this issue, Medical Crossfire recently spoke with Rhoda H. Cobin, MD, FACE, who is Associate Clinical Professor of Medicine at Mt. Sinai School of Medicine in New York, and President Elect of the American Association of Clinical Endocrinologists.

Editor’s Note: The scientific advisory panel of the National Toxicology Program Board of Scientific Counselors did not respond to invitations to participate in this exchange.

Medical Crossfire: Should steroidal estrogens be listed as a known cause of cancer in humans?

Dr. Cobin: Absolutely not. If a substance is truly a carcinogen, then, in my opinion, that substance should not be used; if it is used, the greatest caution should be taken. In the case of estrogen, the well-known benefits of this therapy—in most but not all cases—far outweigh its risks. It is true that studies have documented an increased risk of cancer of the endometrium among users of unopposed estrogen.(2) However, it has also been shown that it is possible to reverse this increased risk by adding progesterone to the therapy regimen.(3) Thus the issue of endometrial cancer is avoided both in women who have had hysterectomies as well as in those patients managed with estrogen–progesterone combinations.

There is also reasonable evidence that in some, but not all, studies, the incidence of breast cancer may be minimally increased in women who use estrogen in the postmenopausal period. However, the relative risk for women on estrogen therapy as compared with those not on this therapy appears to be clinically insignificant. For example, a recent article by Santen and colleagues(4) found that the increased risk of breast cancer in women taking a steroidal estrogen and progesterone combination for menopause is 1 in 397, whereas the prevalent incidence of breast cancer is about 1 in 8 or 9.

Furthermore, I would agree with the hypothesis that most breast cancers probably arise from genetic mutations rather than simply growth stimulation. In the majority of women we do not know what cellular mutations may exist or what provokes these mutations. It is very unlikely, however, that estrogen actually induces mutations. On the other hand, there is fairly strong evidence that in the presence of carcinongenic mutations, estrogen acts as a growth stimulator of breast cancer cells.(5-11) Therefore, if a woman has breast cancer or has risk factors such as a family history of the disease, I think it would not be a wise idea to continue giving her estrogen. But saying that a particular woman should not be on estrogen is very different from calling it a carcinogen.

I find labeling steroidal estrogen a cancer-causing agent to be both inflammatory and condescending to physicians. Such a label will unnecessarily frighten women who might have benefited from estrogen into not using it. I know that if someone told me I was about to begin taking a pill that is a known carcinogen, I would certainly not take it. It is true that estrogen is not appropriate for all women. But to put a label of carcinogen on steroidal estrogen will prevent women who could benefit from estrogen therapy from even considering it.

Medical Crossfire: What impact will this action have on the dialogue between physicians and their patients?

Dr. Cobin: As I previously indicated, I think this action will be seriously detrimental to that dialogue. Carcinogen is such an inflammatory and frightening word that it will close patients’ minds to estrogen therapy even before they speak with their physicians. The result will be that opportunities to help women who may benefit from estrogen—whether it be for osteoporosis prevention, cardiac protection, or quality-of-life issues related to menopause such as hot flashes or vaginal dryness—will be lost. Women who hear that estrogen has been labeled a carcinogen will be unlikely to even entertain the thought of using this therapy.

Medical Crossfire: What recommendations do you have for primary-care physicians when speaking to their patients about estrogen?

Dr. Cobin: Whether the physician is a primary-care doctor, a gynecologist, or an endocrinologist, she should treat each woman as an individual and counsel her about the benefits and risks of estrogen therapy for her. For example, an encounter may begin with a physician acknowledging what she perceives to be the patient’s statistical risk of breast cancer (i.e., low, neutral, or high, based on the patient’s risk factors). This can then be followed by an explanation of what the perceived benefits of the therapy will be. During the encounter, physicians should also be sure to emphasize that the all-cause mortality of women taking estrogen is far lower than that of women who do not take it. The bottom line is that each woman needs to be counseled individually, and as physicians perform this counseling they need to place the risks and benefits of estrogen into perspective for the individual patient.

References

1. Advisory Panel on Federal Report on Carcinogens Makes Recommendations to NIEHS/NTP for New Listings. National Institute of Environment Health Sciences press release; December 15, 2000. Available at: www.niehs.nih.gov/oc/news/rocrslt.htm. Accessed February 14, 2001.

2. The Writing Group for the PEPI Trial. Effects of hormone replacement therapy on endometrial histology in postmenopausal women: the Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial. JAMA. 1996:275:370-375.

3. AACE medical guidelines for clinical practice for management of menopause, Endocrine Practice. 1999;5:354-366.

4. Santen RJ, Pinkerton J, McCartney C, et al. Risk of breast cancer with progestins in combination with estrogen as hormone replacement therapy. J Clin Endocrinol Metab. 2001;86:16-23.

5. Collaborative Group on the Hormonal Factors in Breast Cancer. Breast cancer and hormone replacement therapy: collaborative reanalysis of data from 51 epidemiological studies of 52,705 women with breast cancer and 108,411 women without breast cancer. Lancet. 1997;350:1047-1059.

6. Newcomb PA, Longnecker MP, Storer BE, et al. Long-term hormone replacement therapy and risk of breast cancer in post-menopausal women [published erratum appears in Am J Epidemiol. 1996;143:527]. Am J Epidemiol. 1995;142:788-795.

7. Willis DB, Calle EE, Miracle-McMahill HI, Heath CW Jr. Estrogen replacement therapy and risk of fatal breast cancer in a prospective cohort of postmenopausal women in the United States. Cancer Causes Control. 1996;7:449-457.

8. Schairer C, Gail M, Byrne C, et al. Estrogen replacement therapy and breast cancer survival in a large screening study. J Natl Cancer Inst. 1999;91:264-270.

9. Gapstur SM, Morrow M, Sellers TA. Hormone replacement therapy and risk of breast cancer with a favorable histiology: results of the Iowa Women’s Health Study. JAMA. 1999;281:2091-2097.

10. Prichard TJ, Pankowsky DA, Crowe JP, Abdul-Karim FW. Breast cancer in a male-to-female transsexual: a case report. JAMA. 1988;259:2278-2280.

11. Sellers TA, Mink PJ, Cerhan JR, et al. The role of hormone replacement therapy in the risk for breast cancer and total mortality in women with a history of breast cancer. Ann Intern Med. 1997;127:973-980.

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From NIH: New target=_blank>http://www.nih.gov/news/pr/dec2002/niehs-1...gt;New Federal Report on Carcinogens Lists Estrogen Therapy, Ultraviolet, Wood Dust

The federal government today published its biennial Report on Carcinogens, adding steroidal estrogens used in estrogen replacement therapy and oral contraceptives to its official list of known human carcinogens. This and 15 other new listings bring the total of substances in the report, known or reasonably anticipated to pose a cancer risk, to 228. This, the tenth edition of the report, was forwarded to Congress and released to the public today by the Department of Health and Human Services. It was prepared by the National Toxicology Program, an arm of the HHS located at the National Institute of Environmental Health Sciences, one of the National Institutes of Health. The reports are published every two years after lengthy study and scientific reviews by three successive expert panels of government and non-government scientists.

In a statement releasing the report, HHS Secretary Tommy Thompson today thanked the hundreds of scientists who have contributed to this report through their original research or their careful reviews of these important studies. The public is well served by this dispassionate report that helps all of us ensure that the American public is made aware of potential cancer hazards.

The tenth report newly lists the group of hormones known as steroidal estrogens as known human carcinogens. A number of the individual steroidal estrogens were already listed as reasonably anticipated carcinogens in past editions, but this is the first report to so list all these hormones, as a group. As with all the other medications listed, the Report on Carcinogens does not address or attempt to balance potential benefits of use of these products.

Also newly listed as known causes of cancer in humans are broad spectrum ultraviolet radiation, whether generated by the sun or by artificial sources; wood dust created in cutting and shaping wood; nickel compounds and beryllium and its compounds commonly used in industry. Beryllium and beryllium compounds are not new to the list but was previously listed as reasonably anticipated to be a human carcinogen.

The report is mandated by Congress as a way for the government to help keep the public informed about substances or exposure circumstances that are known or are reasonably anticipated to cause human cancers. The report also identifies current regulations concerning these listings in an attempt to address how exposures have been reduced.

The report makes a distinction between known human carcinogens, where there is sufficient evidence from human studies and reasonably anticipated human carcinogens, where there is either limited evidence of carcinogenicity from human studies and/or sufficient evidence of carcinogenicity from experimental animal studies.

The report does not assess the magnitude of the carcinogenic risk, nor does it address any potential benefits of listed substances such as certain pharmaceuticals. Listing in the report does not establish that such substance presents a risk to persons in their daily lives. Such formal risk assessments are the responsibility of Federal, State, and local health regulatory agencies.

Newly listed as known human carcinogens are:

Steroidal estrogens. These are a group of related hormones that control sex and growth characteristics and are commonly used in estrogen replacement therapy to treat symptoms of menopause and in oral contraceptives. The report cites data from human epidemiology studies that show an association between estrogen replacement therapy and a consistent increase in the risk of endometrial cancer (cancer of the endometrial lining of the uterus) and a less consistent increase in the risk of breast cancer.

As for the other common use for steroidal estrogens, the report says the evidence suggests estrogen-containing oral contraceptives may be associated with an increased risk of breast cancer but may protect against ovarian and endometrial cancers.

Broad Spectrum Ultraviolet Radiation (UVR). UVR is produced by the sun as part of solar radiation and by artificial sources such as sun lamps and tanning beds, in medical diagnosis and treatment procedures, and in industry for promoting polymerization reactions. The report cites data indicating a cause-and-effect relationship between this radiation and skin cancer, cancer of the lip and melanoma of the eye. The report goes on to say that skin cancers are observed with increasing duration of exposure and for those who experience sunburn. The individual components of UVR, which includes ultraviolet A, ultraviolet B and ultraviolet C radiation, are listed in the report, not as known, but as reasonably anticipated human carcinogens — See below.

Wood dust. Listed as a known human carcinogen in this report, wood dust is created when machines and tools cut, shape and finish wood. Wood dust is particularly prevalent in sawmills, furniture manufacture and cabinet making. According to the report, unprotected workers have a higher risk of cancers of the nasal cavities and sinuses.

Nickel compounds. Used in many industrial applications as catalysts and in batteries, pigments and ceramics, the report newly lists nickel compounds as known human carcinogens based on studies of workers showing excess deaths from lung and nasal cancers and on their mechanisms of action.

One group of substances was upgraded from reasonably anticipated to known human carcinogen:

Beryllium and beryllium compounds. About 800,000 workers are exposed via inhalation of beryllium dust or dermal contact with products containing beryllium. Workers with the highest potential for exposure include beryllium miners, beryllium alloy makers and fabricators, ceramics workers, missile technicians, nuclear reactor workers, electric and electronic equipment workers, and jewelers. According to data cited in the report, they have higher risks for lung cancer which increase with their exposures and which cannot be explained by tobacco smoking or other occupational exposures.

Twelve substances or groups of substances are newly listed as reasonably anticipated to be human carcinogens:

IQ, or 2-amino-3-methylimidazo[4,5-f]quinoline, which is formed during direct cooking with high heat of foods such as meats and eggs and also found in cigarette smoke, is listed as reasonably anticipated to be a human carcinogen based on long-term animal studies. The report also states there are several published human studies that suggest there is an increased risk for breast and colorectal cancers related to consumption of broiled or fried foods that may contain IQ and/or other similar compounds formed during cooking at high temperatures.

2,2-bis-(Bromomethyl)-1,3-propanediol (technical grade), a flame retardant chemical used to make some polyester resins and rigid polyurethane foam is listed as reasonably anticipated based on long-term animal feeding studies.

Ultraviolet A, Ultraviolet B and Ultraviolet C Radiation, are listed as reasonably anticipated to be human carcinogens because, according to the report, animal studies show a cause-and-effect relationship between exposure to each of these wavelength groups of broad spectrum ultraviolet radiation (UVR) and skin cancer. The report points out that the data on skin cancer in humans for these different wavelengths of UVR are limited, because it has been impossible to determine if the people in these studies were exposed to pure individual components of UVR or, as is more likely the case, to mixtures of the different components thus making it impossible to say that the observed skin cancers were due only to one of the pure individual components.

Chloramphenicol. An antibiotic with restricted use in the US because it can cause fatal blood disorders, is listed in the report as reasonably anticipated to be a human carcinogen. The report says the listing is based on limited evidence from human studies that showed an increased cancer risk for the occurrence of leukemia after chloramphenicol therapy.

2,3-Dibromo-1-propanol, a chemical used as an intermediate in the production of flame-retardants, insecticides, and pharmaceuticals, is listed in the report as reasonably anticipated to be a human carcinogen based on strong evidence of cancer formation from skin painting study in experimental animals.

Dyes metabolized to 3,3'-dimethoxybenzidine are dyes that have been used to color leather, paper, plastic, rubber and textiles and are listed in the report because they are metabolized to 3,3'-dimethoxybenzidine, which is reasonably anticipated to be a human carcinogen.

Dyes metabolized to 3,3'-demethylbenzidine are dyes that have been used in printing textiles, in color photography and as biological stains and are listed in the report because these dyes are metabolized to 3,3'-dimethylbenzidine, which is reasonably anticipated to be a human carcinogen.

Methyleugenol, occurs naturally in oils, herbs and spices and is used in smaller amounts in its natural or synthetic form in flavors, insect attractants, anesthetics and sunscreens. It is listed in the report based on sufficient evidence of cancer formation from oral studies of this chemical in experimental animals.

Metallic nickel, this metal is used mainly in alloys with most exposures by inhalation or skin contact in the workplace. (It should be noted that metallic nickel is not contained in the nickel coin.) It is listed in the report based on sufficient evidence of cancer formation from studies of this chemical in experimental animals.

Styrene7,8-oxide, is used in producing reinforced plastics and as a chemical intermediate for cosmetics, surface coatings, agricultural and biological chemicals. It is listed in the report based on sufficient evidence of cancer formation from studies of this chemical in experimental animals.

Vinyl bromide, which has been used in polymers in making fabrics for clothes and home furnishings, as well as in leather and metal products, drugs and fumigants. It is listed in the report based on sufficient evidence of cancer formation from studies of this chemical in experimental animals.

Vinyl fluoride, which is used in making polyvinyl fluoride and related weather-resistant fluoropolymers. Support for the listing came from inhalation studies in experimental animals. It is listed in the report based on sufficient evidence of cancer formation from studies of this chemical in experimental animals.

The report is immediately accessible at http://ntp-server.niehs.nih.gov.

For available hard copies, email ehponline@niehs.nih.gov, visit http://www.ehponline.org or write Environmental Health Perspectives, Attn: Order Processing, 1001 Winstead Drive, Suite 355, Cary, NC 27513. Requests for hard copies may also be faxed to (919) 678-8696.

Fact sheets — What is the Report On Carcinogens? and Q and A on the RoC as well as background documents for the new listings — can be accessed at http://ntp-server.niehs.nih.gov/.