Testosterone Therapy and Prostate
(The following is adapted from an excellent lecture by urologist Kenneth Janson, MD, FACS, given at the November 2010 Age Management Medical Group conference, Las Vegas)
In the past it was accepted belief that raising testosterone would increase the risk of prostate cancer. This was largely because in 1941 Huggins, Hodges and Scott showed that orchiectomy (surgical castration) caused regression of prostate cancer.
In 1966 Huggins won the Nobel Prize for “fundamental discoveries concerning the hormone dependence of normal and neoplastic cells in animals, and their practical application to the treatment of human prostatic and breast cancer.”
This led to many years of unchallenged belief that raising testosterone would increase the risk of prostate cancer.
In 1981 Fowler and Whitmore re-opened the discussion: they did a study showing that in men with prostate cancer who were treated with chemical castration (i.e. given medicine to shut down all testosterone production), testosterone therapy caused disease progression, just like Huggins and Hodges had shown. However testosterone therapy in NON-castrated men did NOT cause progression. (In other words: in men that still had some testosterone of their own, adding more did not cause prostate cancer progression.)
Fowler, J, Whitmore, W. The Response of Metastatic Adenocarcinoma of the Prostate to Exogenous Testosterone. J. Urology 1981, 126:372-375
Some questions started to be asked about the assumption that testosterone therapy is always bad in prostate cancer:
In 2000, articles from the Massachusetts Male Aging Study were published showing no correlation between PSA and testosterone levels even with testosterone levels up to 2800ng/dL. (For perspective, Age Management Medicine protocols generally do not push levels past 1200ng/dL, so this study went more than double the typical maximum levels for HRT.)
Massachusetts Male Aging Study, Diabetes Care 2000; 23: 490-4.
Hoffman, M, DeWolf, W, Morgentaler, A. Is Low Serum Free Testosterone a Marker for High Grade Prostate Cancer. J. Urology 2000,163:824-827
In 2002 the Mayo Clinic stated, “There is no clinical evidence that testosterone replacement causes prostate cancer.” Mayo Clin Proc 2002 Jan:75:583-87
In 2004 the U.S. Institute of Medicine agreed, saying there is “No compelling evidence that exogenous Testosterone increases the risk of prostate cancer.”
In 2004 Harvard urologists Morgentaler and Rhoden published an article in the New England Journal of Medicine. The article stated:
“None of the 12 longitudinal population based studies, such as the Physician’s Health Study, found any increased risk of prostate cancer in men with higher levels compared to men with lower levels of testosterone.”
“Despite decades of research, there is no compelling evidence that testosterone has a causative role in prostate cancer. There is no compelling evidence to suggest that high testosterone levels or testosterone administration increases the risk of cancer. Prostate cancer becomes more relevant at the time of a man’s life when testosterone levels decline. Experienced clinicians aim for the upper normal range, in order to optimize treatment.”
Rhoden E, Morgentaler, A. Risks of Testosterone-Replacement Therapy and Recommendations for Monitoring. New England Journal of Medicine 2004,350:482-492
In 2009, Dr. Morgentaler went a bold step further: he published a case report of an 84-year old attorney who was diagnosed with prostate cancer and decided to not treat it and to remain on testosterone therapy. After 24 months his PSA decreased and his prostate cancer was deemed stable:
Morgentaler, A. Two years of Testosterone Therapy Associated with Decline in Prostate-specific Antigen in a man with Untreated Prostate Cancer. J. Sexual Medicine 2009,6:574-577
Morgentaler proposed the Saturation Theory: in patients with NO testosterone (chemically castrated or levels less than 70ng/dL), testosterone replacement may cause disease progression—that first little bit may stimulate receptors on the cancer. HOWEVER, those receptors quickly saturate; therefore if patients are NOT castrated, and have testosterone already circulating, then additional testosterone doesn’t stimulate the receptors any further.
1. Morgentaler, A. Guilt by Association: A Historical Perspective on Huggins, Testosterone Therapy and Prostate Cancer. J Sex Med 2008, 5:1834-1840
2. Morgentaler, A. Testosterone Therapy in Men with Prostate Cancer: Scientific and Ethical Considerations. J. Urology 2009, 181:972-979
3. Morgentaler, A. Shifting the Paradigm of Testosterone and Prostate Cancer: the Saturation Model and the Limits of Androgen-Dependent Growth. European Urology 55 (2009) 310-321
That same year (2008) Cornell, Baylor and University of Toronto published a study showing that Testosterone therapy in hypogonadal men after radical prostatectomy for prostate cancer resulted in NO increase in PSA and NO increase in prostate cancer progression.
Roddam, A and the Endogenous Hormones and Prostate Cancer Collaborative Group. J National Cancer Institute 2008, 100:170-183
Also that year, Marks et al published a study showing that tissue levels of Testosterone in the prostate were tested before and after testosterone therapy, and even though blood levels of testosterone went up significantly, there was no change in testosterone levels in the prostate:
Marks LS, Mazer NA, Mostaghel E. et al. Effect of testosterone replacement therapy on prostate tissue in men with late-onset hypogonadism: a randomized controlled trial. JAMA 2006; 296: 2351.
Most current research:
2010 American Urological Association published work by Morgentaler showing 13 patients already diagnosed with Prostate Cancer who were treated with testosterone replacement and followed for 30 months: they showed no progression of prostate cancer on subsequent biopsies and no increase in PSA.
Morgentaler A, Morales A: Should hypogonadal men with prostate cancer receive testosterone? J Urology, October 2010, 184; 1257-1260.
Furthermore: there is significant evidence to suggest that LOW testosterone INCREASES the risk of prostate cancer:
1. Schatzl et al. High-grade prostate cancer is associated with low serum testosterone levels. Prostate 47:52-58, 2001.
2. In 2006 Morgentaler and Rhodes published a paper showing that low levels of testosterone actually increase the risk of prostate cancer:
Among 345 hypogonadal men with low levels of total or free testosterone, Prostate cancer was present in more than 1 of 7 of the men even though their PSA was less than 4.0. “An increased risk of prostate cancer was associated with more severe reductions in testosterone.”
Morgentaler A, Rhoden E. Prevalence of Prostate Cancer Among Hypogonadal Medn with PSA levels of 4.0ng/mL or Less. Urology 68:1263-1267, 2006.
3. In the Baltimore Longitudinal Study of Aging: Men with the highest levels of Testosterone were at the LOWEST risk of developing prostate cancer.
Laughlin GA, Barrett-Connor E and Bergstrom J: Low serum testosterone and mortality in older men. J Clin Endocrinol Metab 2008; 93: 68.
And, even more recently:
4. Bo Sung Shin, et al: Is a Decreased Serum Testosterone Level a Risk Factor for Prostate Cancer? A Cohort Study of Korean Men Korean J Urol. 2010 December; 51(12): 819–823.
A total of 568 patients who underwent prostate biopsy were entered in this study. Patients with lower levels of serum testosterone had a higher risk of prostate cancer than did patients with high serum testosterone.
IT IS IMPORTANT TO UNDERSTAND that clinical tumor recurrence or increase in PSA DOES OCCUR in a small percentage of patients treated with testosterone— but the rate is NOT higher than previously published statistics in men not receiving testosterone. In other words: whether they get testosterone or not, some men will get (initial or recurrent) prostate cancer. The literature simply indicates that testosterone replacement is not the cause.
In any patient on long-term testosterone replacement therapy, it is important to carefully monitor PSA levels, and regular prostate exam is necessary. Referral to a Urologist is warranted for any concerns. At present, most Urologists who are also trained in Age Management Medicine (a small group, to be sure) would likely NOT stop testosterone therapy even if PSA went up, but that decision would of course be made by the patient after an informed discussion with his doctors.
In the interest of balance it should be noted that, as of this writing, the Endocrine Society Clinical Guidelines still state that testosterone therapy is contraindicated in patients with prostate cancer.
Bio-identical progesterone is not only safe—it protects women from cancer of the breast, ovaries and uterus! Every post-menopausal woman should be on bio-identical progesterone, even if she has had a hysterectomy, because it is protective against breast cancer and ovarian cancer, and has a number of other health benefits as well.
Here are some of the many papers showing that natural progesterone is completely different from synthetic Provera® (aka medroxyprogesterone acetate or “MPA”):
Journal of Steroid Biochemistry and Molecular Biology, July 2005
“The addition of natural progesterone does not affect breast cancer risk. This finding is consistent with in vivo data suggesting that progesterone does not have a detrimental effect on breast tissue. More importantly, medroxyprogesterone acetate [Provera®] can potentiate the proliferative action of estrogens.”
Progestins and progesterone in hormone replacement therapy and the risk of breast cancer. Campagnoli et al. J Steroid Biochem Mol Biol. 2005 Jul;96(2):95-108.
Journal of Steroid Biochemistry and Molecular Biology, December 2005
“…synthetic progestins (i.e. Provera®), when added to HRT for menopausal complaints, increase breast cancer risk more than estrogen alone. However, recent findings suggest that natural progesterone, whether produced during pregnancy or administered outside pregnancy, does not increase breast cancer risk, and could even be protective.” J Steroid Biochem Mol Biol. 2005 Dec;97(5):441-50
Breast Cancer Research and Treatment, 2008
This was a large prospective cohort study of over 100,000 women in France. About 70% of the women used HRT for about 7 years, starting at age 52 (on average). They were then followed for about 8 years. This study found that if they used estrogen alone, without progesterone, they had an increased risk of breast cancer (RR= 1.29). (This was in contrast to the Women’s Health Initiative and the Nurses’ Health Study, both of which found no increased risk of breast cancer with estrogen alone.) If they combined estrogen with synthetic progestins (Provera® /MPA or norethindrone), the risk of cancer was much worse—relative risk of 1.48 to 2.11!
However if they combined estrogen with natural progesterone instead of Provera®, the relative risk of breast cancer was 1.00: no increased risk.
Breast Cancer Res Treat. 2008 Jan;107(1):103-11. Unequal risks for breast cancer associated with different hormone replacement therapies: results from the E3N cohort study.
International Journal of Cancer, 2005
This study assessed the risk of breast cancer in relation to different types of Hormone Replacement Therapy (HRT) in 54,548 postmenopausal women who were part of the E3N-EPIC cohort study.
The relative risk (RR) of developing breast cancer was 1.1 if they used estrogens alone, 1.4 when used in combination with synthetic progestins (such as MPA/Provera), and 0.9 when estrogen was combined with micronized (bio-identical) progesterone. There was little increase in risk with estrogen used alone, and no increased risk when combined with bio-identical progesterone. However when combined with synthetic progestins, even short-term use of estrogens may increase breast cancer risk. Relative risk of breast cancer did not vary according to the route of administration of estrogen (oral vs. transdermal).
Int J Cancer. 2005 Apr 10;114(3):448-54.
(In the image above, TD-E2 stands for Transdermal Estrogen.)
To evaluate the risk of breast cancer associated with the use of estradiol plus (bio-identical) progesterone, which is commonly prescribed in France (rather than MPA/Provera), a cohort of 3175 postmenopausal women was followed for a mean of 8.9 years (28,367 woman-years). They were unable to detect any increase in the risk of breast cancer in the natural, bio-identical hormone users (RR 0.98, 95% confidence interval (CI): 0.65-1.5). (HRT with natural estradiol and natural progesterone) is beneficial for quality of life, prevention of bone loss and cardiovascular risk profile. de Lignières B et al. Combined hormone replacement therapy and risk of breast cancer in a French cohort study of 3175 women. Climacteric. 2002 Dec;5(4):332-40.
Hormone replacement therapy (HRT) in young postmenopausal women is a safe and effective tool to counteract climacteric symptoms and to prevent long-term degenerative diseases, such as osteoporotic fractures, cardiovascular disease, diabetes mellitus and possibly cognitive impairment. However, the expert selection of specific compounds, doses or routes of administration can provide significant clinical advantages. Recent evidence shows that natural progesterone displays a favorable action on the vessels and on the brain, while this might not be true for synthetic progestins (like Provera®). …Recent trials (also) indicate that… natural progesterone confers less or even no risk of breast cancer, as opposed to synthetic progestins. Maturitas. 2008 Jul-Aug;60(3-4):185-201. Could transdermal estradiol + progesterone be a safer postmenopausal HRT? A review.
The Journal of Reproductive Medicine, 1999
Endometrial hyperplasia. Risks, recognition and the search for a safe hormone replacement regimen:
“The synthetic progestins have been associated with uncomfortable side effects, reversal of some of the cardiovascular and metabolic benefits of estrogen, and unwanted bleeding. The use of natural progesterone alleviates the former two drawbacks… In Europe, where natural progesterone has been in use for some time, a cyclic combined regimen of estrogen and 100mg micronized progesterone administered on days 1-25 has been shown to decrease the risk of uterine cancer, with minimal bleeding and a high rate of tolerability.” J Reprod Med. 1999 Feb;44:191-6.
(Note: While the above regimen can be used, and is safe, I would simply continue the progesterone daily rather than cycle it. This prevents withdrawal bleeding (most women would rather not go back to getting their period!) and affords the protective benefits of progesterone on uterus, breast and ovaries every day rather than just 25 days a month.– Trutt)
A 3-year, multicenter, randomized, double-blind, placebo-controlled trial involving 875 healthy postmenopausal women aged 45 to 64 years: The PEPI Trial.
Estrogen with natural bio-identical progesterone has the most favorable effect on HDL-C (compared to synthetic MPA) and no increased risk of endometrial cancer.
Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women. The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial. JAMA. 1995 Jan 18;273(3):199-208.
Breast Cancer Research and Treatment, 2007
The goal of this study was to compare the effects of oral estradiol given with either MPA or micronized progesterone on risk for breast cancer in a postmenopausal primate model. Compared to placebo, Estrogen + MPA resulted in significantly greater breast tissue proliferation, while Estrogen + bio-identical progesterone did not. These findings suggest that oral micronized progesterone has a more favorable effect on risk biomarkers for breast cancer than medroxyprogesterone acetate. These findings provide growing support for micronized progesterone as an alternative to MPA in hormone therapy regimens.
Effects of estradiol with micronized progesterone or medroxyprogesterone acetate on risk markers for breast cancer in postmenopausal monkeys. Breast Cancer Res Treat. 2007 Jan;101(2):125-34.
Cancer prevention is not the only area where natural progesterone has the opposite effect of synthetic Provera®: they also have opposite effects when it comes to preventing heart disease and stroke:
“All women on micronized progesterone had a decrease in total cholesterol and an increase in high-density lipoprotein cholesterol. Those on MPA (Provera®) had no significant change in total cholesterol. Progesterone increases estrogen’s beneficial effects on cholesterol, whereas MPA reverses estrogen’s benefits.”
Hargrove JT, Maxson WS, Wentz AZ, Burnett LS. Menopausal hormone replacement therapy with continuous daily oral micronized estradiol and progesterone. Obstet Gynecol. 1998 Apr;73(4):606-612.
“Estrogen and progesterone are neuro-protective against cerebral damage. These beneficial effects were blocked by MPA (medroxyprogesterone).” National Academy Science USA; 2003 Sept. 2;100(8):10506-11.
“Progesterone raises good HDL cholesterol, whereas MPA (Provera®), lowers good cholesterol. Progesterone increases estrogen beneficial effects whereas MPA reverses estrogen’s benefits. Progesterone has no side effects, whereas MPA has many.” Obstetrics Gynecology 1989;73:606-611.
““Due to the side effects of synthetic progestins, natural progesterone is preferred. Progesterone has proven bio-availability and no side effects, making it the preferred hormone for menopause.”” American Family Physician 2000; 62:1939-1946
“Synthetic progestin’s (like Provera®) cause many side effects: breast swelling and tenderness, uterine bleeding, depression and mood disturbance, weight gain, bloating and edema. Natural progesterone has no side effects.” Female Patient 2001 Oct; 19-23.
“Progesterone may have a protective role against the atherosclerotic changes associated with type II diabetes.”
Carmody BJ, Arora S, Wakefield MC, Weber M, et al. Progesterone inhibits human infragenicular arterial smooth muscle cell proliferation induced by high glucose and insulin concentrations. J Vasc Surg. 2002 Oct; 36(4):833-888.
Elevated serum progesterone concentrations were associated with a statistically significant reduction in breast cancer risk (OR for highest versus lowest quartile = 0.61, 95% CI = 0.38 to 0.98; P(trend) = .06). J Natl Cancer Inst. 2005 May 18;97(10):755-65. Serum sex steroids in premenopausal women and breast cancer risk within the European Prospective Investigation into Cancer and Nutrition (EPIC).
Cancer Epidemiology, Biomarkers and Prevention, 2002
This study directly evaluated the association between progesterone levels during third trimester of pregnancy and maternal risk of developing breast cancer later in life. Elevated progesterone levels were associated with a decreased incidence of breast cancer [odds ratio (OR) for progesterone >/=270 ng/ml, 0.49; 95% confidence interval (CI), 0.22-1.1] relative to those in the lowest decile.
(Note that the levels during pregnancy are close to 300ng/dL, and that is clearly safe for the mother as well as protective against breast cancer. Age Management protocols in post-menopausal women maintain serum progesterone levels at a minimum of 10ng/dL. Although that seems quite low in relation to the levels during pregnancy, Progesterone creams are nevertheless unable to accomplish this. Sublingual or oral progesterone is the way to go, contrary to what some websites may say.– Trutt)Steroid hormone levels during pregnancy and incidence of maternal breast cancer. Cancer Epidemiol Biomarkers Prev. 2002 Apr;11(4):361-8.
The following three papers show that having low progesterone levels increases the risk of breast cancer. This is particularly relevant to women with PolyCystic Ovary Syndrome (PCOS), which involves a deficiency of progesterone. These women have an increased risk of breast cancer if not appropriately treated.
International Journal of Cancer, 2004
Endogenous sex hormones and subsequent breast cancer in premenopausal women:
This study recruited 5,963 premenopausal women to the Hormones and Diet in the Etiology of Breast Tumors (ORDET) cohort study; they provided a blood sample in the 20-24th day of their menstrual cycle. After 5.2 years of follow-up, 65 histologically confirmed breast cancer cases were identified and matched to randomly selected controls.
Progesterone was inversely associated with adjusted Relative Risk for breast cancer– so much so that in women with regular menses (i.e. higher levels of progesterone), adjusted RR was just 0.12! (95% CI = 0.03-0.52, p for trend = 0.005). These findings support the hypothesis that ovarian hyperandrogenism associated with luteal insufficiency increases the risk of breast cancer in premenopausal women. Int J Cancer. 2004 Nov 1;112(2):312-8.
(NOTE: “ovarian hyperandrogenism associated with luteal insufficiency” is medical-ese for Polycystic Ovary Syndrome (PCOS) —Trutt.)
American Journal of Epidemiology, 1981
Researchers at Johns Hopkins studied 1083 women who had been evaluated for infertility from 1945-1965 and were followed prospectively through 1978 to ascertain their breast cancer incidence. These women were categorized as to the cause of infertility into two groups: those with progesterone deficiency (PD) and those with nonhormonal causes (NH). Women with progesterone deficiency had 5.4 times the risk of premenopausal breast cancer. Women with progesterone deficiency also experienced a 10-fold increase in deaths from allmalignant neoplasms compared to women in the NH group. The incidence of postmenopausal breast cancer did not differ significantly between the two groups.
Cowan LD et al. Breast cancer incidence in women with a history of progesterone deficiency. Am J Epidemiol. 1981 Aug;114(2):209-17
Breast Cancer research and Treatment, 1986
Estrogen and progesterone, when secreted in an adequate balance, permit the complete and proper development of the mammary gland. Progesterone may also have an antagonistic activity against estradiol, mediated through a decrease in the replenishment of the estrogen receptor, and also through increased 17 beta-hydroxysteroid dehydrogenase which leads to accelerated metabolism of estradiol to estrone… Thus, it can be inferred that long periods of luteal phase defect (i.e progesterone deficiency/ anovulation as is seen in PCOS) leading to an unopposed estrogen effect on the breast might promote breast carcinogenesis. Breast Cancer Res Treat. 1986;8(3):179-88 Mauvais-Jarvis P, et al. Antiestrogen action of progesterone in breast tissue.
LAB STUDIES: The following papers discuss in vitro (lab, not human) studies that explain how progesterone protects against cancer.
“Progesterone alone or combined with estradiol induces cellular apoptosis (kill breast cancer cells).”
Franke HR, Vermes I. Differential effects of progestogens on breast cancer cell lines. Maturitas. 2003 Dec; 46(1):S55-58.
Molecular and Cell Biochemistry, 1999
Progesterone inhibits the proliferation of normal breast epithelial cells in vivo, as well as breast cancer cells in vitro. We explored the possibility that an antiproliferative activity of progesterone in breast cancer cell lines is due to its ability to induce apoptosis…These results demonstrate that progesterone at relative high physiological concentrations, comparable to those seen during the third trimester of human pregnancy, exhibited a strong antiproliferative effect on breast cancer cells and induced apoptosis.
Mol Cell Biochem. 1999 Dec;202(1-2):53-61. Bcl-2, survivin and variant CD44 v7-v10 are downregulated and p53 is upregulated in breast cancer cells by progesterone: inhibition of cell growth and induction of apoptosis.
Journal of Cell Biochemistry, 2001
Apoptosis induced by progesterone in human ovarian cancer cell line SNU-840:
Progesterone has been used as an ingredient of anticancer drug for patients with ovarian carcinoma. In this study, the effects of progesterone on ovarian cancer cells, SNU-840, were investigated. …The level of the p53 mRNA reached its maximum at 12 h after incubation with progesterone. …Progesterone inhibits the proliferation and elicits apoptosis of human ovarian cancer SNU-840 cells. Also, it up-regulates p53 mRNA transiently. J Cell Biochem. 2001;82(3):445-51.
European Journal of Cancer Prevention, 2002
“These results suggest that MCF-7 human breast cancer cells become more sensitive to progesterone and die by apoptosis due to inhibition of the PI3-kinase/Akt pathway.” Eur J Cancer Prev. 2002 Oct;11(5):481-8. Alkhalaf M et al.
FEBS Letter, 2005
Progesterone inhibits human breast cancer cell growth through upregulation of CDK inhibitor p27Kip1 gene.
“Progesterone derivatives selectively activating the p27 gene promoter could be promising drugs against breast cancer progression.” FEBS Letter 2005 Oct 24; 579(25):5535-41
American Journal of Physiology-Endocrinology and Metabolism, 2005
This in-vitro study suggests that bio-identical progesterone together with estrogen is actually more protective against breast cancer than just progesterone alone: Progesterone increases the production of something called Breast Cancer Resistance Protein, and in combination with estradiol its production is increased even further. Am J Physiol Endocrinol Metab 2005 Dec 13 Regulation of BRCP/ABCG2 Expression by Progesterone And 17beta-estradiol in Human Placental BeWo Cells.
Proceedings of the National Academy of Sciences, 1999
Hormonal prevention of breast cancer: mimicking the protective effect of pregnancy.
Full term pregnancy early in life is the most effective natural protection against breast cancer in women. Because the mammary gland is exposed to the highest physiological concentrations of estradiol and progesterone during full term pregnancy, it is these elevated levels of hormones that likely induce protection from mammary cancer. Thus, it appears possible to mimic the protective effects of pregnancy against breast cancer in nulliparous rats by short term specific hormonal intervention. Guzman RC, et al.Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2520-5.
Japan Journal of Cancer Research, 1985; 76:669-04
Estrogen-induced mammary tumors could be shrunk equally using either Tamoxifen or bio-identical progesterone.
American Journal of Obstetrics and Gynecology, 1999
In women with previous breast cancer, estrogen replacement therapy apparently does not increase cancer recurrences or mortality rates. Adding progesterone may even decrease recurrences. Women with early breast cancer should be offered hormone replacement therapy after a full explanation of the benefits, risks and controversies.
Fertility and Sterility, 1998
Estradiol and progesterone regulate the proliferation of human breast epithelial cells.
Double-blind randomized study to study the effects of estradiol and progesterone on the proliferation of normal human breast epithelial cells in vivo.
METHOD: Daily topical application to both breasts of a gel containing a placebo, estradiol, progesterone, or a combination of estradiol and progesterone during the 14 days preceding esthetic breast surgery or excision of a benign lesion. The surgical procedure allowed them to then measure breast tissue proliferation.
RESULTS: Topical progesterone reduced the estradiol-induced proliferation of normal breast epithelial cells by 400% and down-regulated breast receptor sites to reduce breast cancer risks.
Foidart JM, Colin C, Denoo X, Desreux J, et al. Estradiol and progesterone regulate the proliferation of human breast epithelial cells. Fertil Steril. 1998 May; 69(5):963-969.
Fertility and Sterility, 1995
Estradiol stimulates ductal proliferation 230% — but bio-identical progesterone decreased proliferation 400%!
Fertil Steril. 1995 Apr;63(4):785-91. Influences of percutaneous administration of estradiol and progesterone on human breast epithelial cell cycle in vivo.
The current data supports waiting until you are cancer-free for five years, and then initiating HRT– even if your cancer was ER positive or you have a BRCA1 mutation. The five-year mark is probably somewhat arbitrary, but that is how the studies to date have been done, and it’s best to stick with the literature.
Journal of Obstetrics and Gynaecology Canada, 2004
Use of Hormonal Therapy after treatment of breast cancer.
HRT after treatment of breast cancer has not been demonstrated to have an adverse impact on cancer recurrence or mortality.
J Obstet Gynaecol Can. 2004 Jan
Estrogen replacement therapy in breast cancer survivors: a matched-controlled series.
Estrogen Replacement Therapy relieved estrogen deficiency symptoms and did not increase the rate or time to cancer recurrence, new primary cancer, or systemic metastases. Overall survival favored the ERT group (p=0.02).
Menopause 2003 Jul-Aug: 10(4) 269-70
Medical Journal of Australia, 2002
Hormone Replacement therapy after a diagnosis of breast cancer: cancer recurrence and mortality:
1122 women who had breast cancer and used HRT for up to 26 years, were followed for up to 36 years (median of 6 years). Compared with non-users, HRT users had reduced risk of cancer recurrence and reduced all-cause mortality. Continuous combined HRT was associated with a reduced risk of death from primary tumor (RR 0.32) and all-cause mortality (RR 0.27)
HRT use for menopausal symptoms by women treated for primary invasive breast cancer is not associated with an increased risk of breast cancer recurrence or shortened life expectancy.
MJA 2002 177(7):347-351
Journal of Reproductive Medicine, 2004
A review of literature prior to March 2003 found 1558 breast cancer survivors treated with HRT or Estrogen RT.
In this review, the cancer recurrence rate was 11% in patients who received estrogen and 20% in patients not given estrogen.
J Reprod Med 2004; 49:510-526
American Journal of Obstetrics and Gynecology, 2002
Estrogen Replacement Therapy in Women with Early Breast Cancer
Estrogen replacement therapy apparently does not increase the risk of recurrence or of death in patients with early breast cancer. These patients may be offered estrogen replacement therapy.
Am J Obstet Gynecol 2002 Aug; 187(2):289-94
Journal of the National Cancer Institute, 2001
Hormone Replacement Therapy After a Diagnosis of Breast Cancer in Relation to Recurrence and Mortality
“The rate of breast cancer recurrence was 17 per 1000 person-years in women who used Hormone Replacement Therapy (HRT) after diagnosis, and 30 per 1000 person-years in non-users (of HRT). Breast cancer mortality rates were five per 1000 person-years in HRT users and 15 per 1000 person-years in non-users. Total mortality rates were 16 per 1000 person-years in HRT users and 30 per 1000 person-years in nonusers.
We observed lower risks of cancer recurrence and mortality in women who used HRT than in women who did not.
…the results suggest that HRT after breast cancer has no adverse impact on recurrence or mortality.”
J Natl Cancer Inst 2001 93(10) 754-761
The Journal of Family Practice, 2002
Cancer Recurrence and mortality in women using hormone replacement therapy after breast cancer: Meta-analysis.
This meta-analysis of observational studies found no increased risk of breast cancer recurrence and a statistically significant reduction in mortality for breast cancer survivors who take hormone replacement therapy compared to those who do not.
Meurer et al. The Journal of Family Practice, Dec 2002. Vol 51, No. 12
American Journal of Clinical Oncology, 2000
Breast cancer survival and hormone replacement therapy: a cohort analysis.
The objective of this study is to perform a matched cohort analysis to evaluate the impact of HRT on mortality in breast cancer survivors. Patients with breast cancer who received HRT after diagnosis of breast cancer were identified. Control subjects were identified from the regional cancer registry. Matching criteria included age at diagnosis, stage of breast cancer, and year of diagnosis. Only subjects not included in a previously reported matched analysis were selected. One hundred twenty-five cases were matched with 362 controls. The median duration of HRT was 22 months (range 1-357 months).
The risk of death was lower among the HRT users;
odds ratio 0.28 (95% confidence interval 0.11-0.71). Am J Clin Oncol. 2000 Dec;23(6):541-5.
Breast cancer incidence in postmenopausal women using testosterone in addition to usual hormone therapy.
This retrospective observational study suggests that “the addition of testosterone to conventional HRT for postmenopausal women does not increase and may indeed reduce hormone therapy-associated breast cancer risk.”
Dimitrakakis et al. Menopause Vol 11, No, 5 pp 531-535
Tamoxifen, hormone receptors and hormone replacement therapy in women previously treated for breast cancer: a cohort study.
Objective: To determine the risk of recurrence of breast cancer associated with hormone replacement therapy in women previously treated for breast cancer who were taking Tamoxifen or who were estrogen receptor-positive.
The use of HRT was not associated with an increased risk of recurrence of breast cancer in women taking Tamoxifen or who were estrogen receptor positive.
Dew et al. Climacteric 2002; 5:151-155
American Journal of Obstetrics and Gynecology, 2002
Estrogen Replacement Therapy in patients with early breast cancer
Estrogen Replacement Therapy apparently does not increase the risk of either recurrence or of death in patients with early breast cancer. These patients may be offered ERT after a full explanation of the benefits, risks and controversies.
Am J Obstet Gynecol 2002; 187:289-95
International Journal of Gynecology & Obstetrics, 1999
Estrogen replacement therapy in breast cancer survivors
Twenty-four patients who had previously been treated for breast cancer 8-91 months prior to their initiating ERT have been observed for 24-44 months. There were 15 patients with stage 1, eight with stage 2 and one with stage 4 breast cancer. Two patients had a biopsy of a suspicious breast nodule: both of which were benign. There have not been any recurrences to date.
Breast cancer survivors did not have their outcome adversely affected by Estrogen Replacement Therapy during an observation period of 24-44 months.
Int J Gynecol Obstet. 64 (1999) 59-63