Testosterone added to HRT may protect against breast cancer

[Sassy]

Testosterone added to HRT may protect against breast cancer

Karla Gale
Reuters Health
Last Modified: November 1, 2001
Last Updated: 2004-09-14 16:20:02 -0400 (Reuters Health)
http://www.oncolink.upenn.edu/resources/article.cfm?c=3&s=8&ss=23&id=11074&month=09&year=2004

NEW YORK (Reuters Health) - When added to conventional hormone replacement therapy (HRT), testosterone may reduce the risk of breast cancer in postmenopausal women, results of a small, observational study suggest.

"I hope that this paper stimulates interest in the question of whether a more physiological HRT regimen might have better effects," senior author Dr. Carolyn A. Bondy told Reuters Health. But, she emphasized, "I do not recommend any changes in HRT treatment until we're convinced it's safe and efficacious."

The Women's Health Initiative and the "Million Women" Study, large clinical trials of combined estrogen and progestin HRT, were terminated early when they showed an increased risk of breast cancer (see Reuters Health reports July 9, 2002 and August 7, 2003). However, these studies did not evaluate the potential of combined treatment that included testosterone.

Dr. Bondy, with the National Institutes of Health in Bethesda, Maryland, and colleagues report the results of a retrospective, observational study of women treated with testosterone and estrogen, with or without progestin, for a mean of 5.8 years. Their findings are published in the September/October issue of Menopause.

Included in the study were 508 postmenopausal women who received testosterone implants containing 50 mg to 150 mg testosterone every 5 months, along with oral conjugated estrogens or estradiol implants (n = 161). Women with a uterus also received medroxyprogesterone with or without norethisterone (n = 347).

During follow-up of 0.7 to 11.4 years, there were seven cases of invasive breast cancer (incidence per 100,000 woman years = 238). One case occurred in the group using estrogen and testosterone only (incidence = 115), while six cases and the only death occurred in the group that was also using progestins (incidence = 293).

In comparison, the incidence of breast cancer per 100,000 woman-years in the estrogen and progestin arm of the Women's Health Initiative was 380. The corresponding incidence was 521 among those who used estrogen and progestin in the Million Woman study. However, the incidence among never-users in the Million Woman study was 283.

Prior to menopause, the ovary produces both androgen and estrogen, co-author Dr. Robert A. Jones, at Memorial Medical Center in North Adelaide, South Australia, explained in an interview with Reuters Health. Conventional HRT "stimulates the mammary epithelium directly, and tends to interfere with the protective effect of testosterone," thus increasing the risk of breast cancer.

"If testosterone had been used by subjects in the Women's Health Initiative study, it may have stopped the rise in breast cancer risk," he added. "It's possible the trial would not have needed to be stopped early."

His group's findings also confirm the suspected increased risk when oral progestin is added to estrogen HRT in women who still have a uterus. That issue could possibly be circumvented by administering the progestin via an intrauterine device rather than orally, Dr. Jones said. After all, he commented, "Why give progestin to the breast when all you want to do is give it to the uterus?"

He noted that testosterone has the added bonus of improving a woman's mood, reducing breast soreness, increasing bone density, as well as restoring energy, stamina, and sex drive.

These findings do not prove that testosterone is protective, Dr. Jones added. For that, randomized, controlled trials will be needed.

Dr. Bondy agreed. "I would love to see a clinical trial, especially for younger women who've had their ovaries surgically removed or who have ovarian failure for some other reason, who have to take HRT. Otherwise, they get terrible osteoporosis and their sexual characteristics disappear at a young age."

Until such studies have been completed, she reiterated, "I do not want people to jump on the bandwagon and do something that is unproven."

Menopause 2004;11:531-535.

 

[Sassy]

Hormone Therapy Possibilities for Breast Cancer Survivors and Women at High Risk for

Hormone Therapy Possibilities for Breast Cancer Survivors and Women at High Risk for Cancer
http://www.project-aware.org/Resource/articlearchives/hrt-breastcancer.shtml

by Pete Hueseman R.Ph.,P.D., Consultant Pharmacist
May 2004

Past History of Breast Cancer

Patients with past history of breast cancer should not have estradiol or estrone recommended for estrogen supplementation. These estrogens play a role in causing breast cancer by damaging DNA. Estriol is the protective estrogen that is high during pregnancy. It does not activate the estrogen receptor, but occupies the receptor sites so that it is not available for estradiol. Hormone balance is important, and testing of hormone levels is recommended prior to supplementing. For post breast cancer patients, many medical practitioners do not recommend hormone supplementation, except for progesterone, unless hormone levels are well below normal and symptoms are severe. Use of hormones should be carefully tracked by both patient and doctor.

Here's what we suggest:

Estriol should be recommended (2 mg twice a day) and is thought to reduce the risk of breast cancer recurrence. For atrophy of vaginal tissues and urethral problems in post breast cancer patients, a compounded estriol cream (.5 mg/gram applied topically 2 - 3 times a week) is considered safe.
Progesterone has the effect of down regulation of estrogen receptors in breast and uterine tissue.
Testosterone has been reported in some studies to have an anti-carcinogenic effect on breast cancer cells and in clinical studies has demonstrated increased survival rates for patients receiving testosterone vs. those who did not.
Arimidex prevents aromatization of testosterone to estradiol and aromatization of androstenedione to estrone. The ATAC study has documented Arimidex as better than tamoxifen or placebo for early-stage, hormone-receptor-positive breast cancer. The early ATAC results do suggest that Arimidex might have benefits over tamoxifen, but the decision to start taking Arimidex instead of tamoxifen is not clear-cut at this point.
Two things we know about Arimidex:

Arimidex and tamoxifen should not be taken together. There appears to be no proven advantage to the combination over tamoxifen or Arimidex alone, and you may have side effects from both drugs.
Aromatase inhibitors have no proven role in pre-menopausal women diagnosed with breast cancer.
Indole-3-Carbinol prevents conversion of 2-hydroxyestrone to the carcinogenic 16-hydroxyestrone and 4-hydroxyestrone.
Drug therapy recommendations:

Estriol 2.5 mg + Progesterone 100 mg + Testosterone 1.25 mg. Take one sublingual tablet twice a day.
Arimidex (anastazole) 1 mg tablets. Take one everyday.
Indole-3-carbinol 400 mg. Take one capsule daily.
Certainly a person with an estrogen-receptor-positive tumor is at much higher risk with estradiol treatment than an estrogen-receptor-negative tumor. However, both types of tumors have an elevated risk of recurrence with estradiol treatment.

My thoughts are that a patient with a history of estrogen-receptor-positive tumor should DEFINITELY be on Arimidex for life! She also should not receive estradiol, of course. The other hormones (except DHEA) are fine. The downside for women at risk of breast cancer is that DHEA can convert to estrogen and has a stimulatory effect on breast cells, particularly when estrogen is low. Close watch on overall hormone balance levels is required, and testing is recommended every 6 months. In terms of estrogen receptor negative, I would say that Arimidex is probably not a must.

High Risk for Breast Cancer

A patient with a high risk (based on the Gail Model) for breast cancer would benefit from supplementation of estrogen and progesterone with human identical hormones in ratios similar to those in the human body.

Progesterone is recommended for benefits of fluid balance and protection against cancer. Progesterone has the effect of down regulation of estrogen receptors in the breast.

Patients are also likely to benefit from estriol with its potential for protection against breast cancer recurrence due to its low estrogenic activity, which possibly results in binding to estrogen receptors without stimulation of receptor. This is recommended in a higher ratio of estriol to estradiol than the typical ratio seen in Biest (80%/20%). For patients with a higher risk for breast cancer, we recommend 90%/10% estriol/estradiol.

We also recommend Indole-3-Carbinol to prevent conversion of 2-hydroxyestrone to the carcinogenic 16-hydroxyestrone and 4-hydroxyestrone. This will provide additional protection against breast cancer and should be considered in the patient with positive family history.

Drug Therapy Recommendations:

90% estriol/10% estradiol sublingual tablet. Take one under the tongue twice a day.
Progesterone 100 mg sublingual tablets. Take one under the tongue twice a day.
Indole-3 Carbinol (Cervaplexx I3-C) 400 mg. Take one every day.
In response to the book "The Sexy Years" by Suzanne Somers, we have not found in the last 12 years any significant increase in insulin resistance with continuous therapy. I do not feel it is necessary to cycle therapy if you have been in post-menopause for over one year.

Lastly, in most instances it will be rather difficult for patients to find an endocrinologist in their area to work with them and natural hormone therapy. My suggestion for women would be to use your regular OB-GYN and contact us if the patient needs assistance.

References

Hoover R. Gray LA Cole P. et al: Menopausal estrogens and breast cancer. N Engl J Med 295:401-405, 1976.
Smith LH, Gordon GS Medical staff conference: Postmenopausal osteoporosis. West J Med 125:137-142, 1976.
Halberstam MJ: If estrogens retard osteoporosis, are they worth the cancer risk? Mod Med 45:9, 15, 1977.
Speroff L: The breast as an endocrine target organ.Contemp Obstet Gynec 9:69-72, 1977.
Gold JJ: Figure 5-7 in Gold JJ (ed). Gynecologic Endocrinology, ed 2. New York. Harper & Row Publishers Inc. 1975, p.67.
Ryan KJ: Biosynthesis of ovarian steroids, in Danforth DN (ed): Textbook of Obstetrics and Gynecology, ed 2. New York. Harper & Row Publishers Inc. 1971, pp131-134.
Yen SSC, Martin PL, Burnier NM, et al: Circulating estradiol, estrone and gonadotropin levels following the administration of orally active 17 b-estradiol in postmenopausal women. J Clin Endocrinol Metab 40:518-521, 1975.
Thijssen JHH, Poortman J, Schwarz F, et al: Post-menopausal estrogen production with special reference to patients with mammary carcinoma. Front Horm Res 3:45-62, 1975.
Lauritzen C: The female climacteric syndrome: Significance, problems, treatment, Acta Obstet Gynecol Scand 51 (suppl): 49-61, 1976.
Lauritzen C: The management of the pre-menopausal and the post menopausal patient. Front Horm Res 2: 2-21, 1973.
Bulbrook P.D, Swain MC, Wang DY, et al: Breast cancer in Britain and Japan: Plasma oestradiol-17b, oestrone and progesterone and their urinary metabolites in normal British and Japanese women. Eur J Cancer 12:725-735, 1976.
breastcancer.org - A non-profit organization for breast cancer education discusses Arimidex (ATAC Trial). **broken link removed**
AstraZeneca Oncology - Breast Cancer Healthcare Professional summarizes the Arimdex (anastrozole); ATAC Trial **broken link removed**
Medscape: ATAC trial: Aromatase Inhibitors in the Adjuvant Setting: Available Data. http://www.medscape.com/viewarticle/424077_5
Lemon HM: Estriol prevention of mammary carcinoma induced by 7, 12-dimethylbenzanthracene and procarbazine, Cancer Res 35:1341-1353, 1975.
Gail MH, Brinton LA, Byar DP, Corle DK, Green SB, Schairer C, Mulvihill JJ. Projecting individualized probabilities of developing breast cancer for white females who are being examined annually. J Natl Cancer Inst 1989;81:1879-1886.
Costantino JP, Gail MH, Pee D, Anderson S, Redmond CK, Benichou J, Wieand HS. Validation studies for models projecting the risk of invasive and total breast cancer incidence. J Natl Cancer Inst 1999;91:1541-1548.
Indole-3-carbinol(13c) and Dindolylmethane (DIM) abstracts: **broken link removed**

 

[oldfella]

Good work there Sassy, Your posts are always interesting and full of great info. The study on HRT spplemented with test is of particular interest. It only makes sense to me that some test is required in females to balnce things out. it is a shame that they will not engage in more detailed studies to determine the benefits of this type of HRT regimen. Good read though!