Hormone Replacement Therapy (HRT)

 

PLEASE NOTE:  Estrogen dominance will be experienced when coming off HRT - see here.

 

Synthetic estrogen and, increasingly, bio-identical estrogen, has been prescribed as HRT to women since the 1950's to alleviate some of the symptoms of menopause. By the mid sixties it was being boastfully advertised as the saviour of the menopausal woman, keeping her "Feminine Forever" which is the title of a book by Dr Robert Wilson.

Wyeth Ayerst produced the first conjugated estrogen called Premarin, standing for 'Pregnant Mare's Urine'. It is, as the name suggests, made from pregnant mare's urine. The pregnant horses, some say as many as 80,000, are kept tethered in stalls for six months of the year, fed little water to concentrate the urine, which is collected in bags held under the horses tails. The urine is then processed to yield various hormones, only 40% being human hormones, the potent remainder being horses hormones. It's no wonder most women do not do well on it. About 15% of US women were using it by 2003, and those who do only stay on for an average of one year. The figure now is thankfully much lower.

Initially only estrogen was given, but then an alarming increase in endometrial cancer in the 1970's was observed. A study published in the New England Journal of Medicine, (NEJM) in 1976 noted the increase was greater than 10% in some areas. But for women in middle age the increase varied between 40 to 150%.

As early as 1976 an increase in breast cancer was found, yet estrogen is still recommended for menopause symptoms. An article in Medline cited a study that followed 1891 women for 12 years. Expecting to find 39.1 women to have developed cancer over that time, they found instead 49 had, giving a relative risk of 1.3%. This increased to 2.0% after 15 years. As any woman who has had cancer will confirm the benefits are not worth the risks.

So HRT or 'hormone replacement therapy' was born. Synthetic progesterone, commonly known as 'progestin' or 'progestogen', was added to the estrogen to lessen the risk of endometrial cancer. In the excitement of finding a solution to the rise in endometrial cancer, the rise in breast cancer was conveniently overlooked.

In July 2002, the Women's Health Initiative (WHI) was stopped early as it had revealed that HRT caused an increased risk in both heart disease (higher risks of stroke, heart attack, and blood clots) and breast cancer. About 50% of the users stopped taking the drug.

The good news though is that in 2003 breast cancer rates fell 7% overall and in the 50-69 age group by 12%.  The drop is all the more interesting as breast cancer rates had increased 30% from 1975 to 2000.  The WHI study also found that both estrogen alone or combined with a progestin increased the risk of urinary incontinence.

Between 1996 and 2001 The Million Women Study in the UK found risks were significantly increased for oral, transdermal, and implanted estrogen-only, but substantially greater for estrogen-progestagen. The risk increased for breast, ovarian and endometrial cancer.

HRT was also found to increase fibroid volume within the first 2 years of use.

In 2003 the University of Wisconsin found the use of HRT was associated with a 7% increased risk of endometrial cancer per year of use.

An interesting study was conducted in Brazil in 2004 where it was found transdermal estrogen combined with 100mg vaginal progesterone did not increase the risk of hypertension, and did not affect thrombin, renin or aldosterone levels.

A similar 2004 study in France found a significantly greater risk with HRT containing synthetic progestins, than with HRT containing micronized progesterone.

C-reactive protein (CRP) is a marker for inflammation and is a risk factor for heart disease. In 2004 a study in Italy found a 66% increase for estrogen only users and a 112% increase for those using a combined hormone replacement therapy.

The 2005 Nurses' Health Study found users of HRT had statistically significantly higher estradiol, free estradiol and testosterone than non users. The study revealed that plasma sex hormone concentrations were associated with breast cancer risk among HRT users. They also found a 78% higher risk for developing urinary incontinence.

Further results from the WHI found that after 5 years of taking HRT (Prempro) cognition was impaired and the risk for dementia was doubled.

By 2007 it was found that combined estrogen plus medroxyprogesterone acetate resulted in insulin resistance.

A follow up study of the WHI in 2008 found women who had taken HRT remained at higher risk of breast cancer for three years after stopping. But women taking HRT for one year had a 4% greater risk of having a mammogram with abnormalities and an 11% greater risk after five years. This compromises the results leading to unnecessary biopsies.

In 2009 a study was conducted in Denmark on women between the ages of 50 to 79, checking national registers between the years 1995 to 2005. They concluded "Regardless of the duration of use, the formulation, estrogen dose, regimen, progestin type, and route of administration, hormone therapy was associated with an increased risk of ovarian cancer."

The Lancet published a study in 2009 which found that although HRT did not increase the risk of lung cancer, it increased the number of deaths.

A review by the Cochrane Incontinence Group in 2010 found that both conjugated equine estrogen and a estrogen/progestogen combination caused significant worsening of incontinence.

So HRT, either estrogen alone, but particularly combined with a progestin, increases the risk of:

  • breast, ovarian and endometrial cancer
  • heart disease including strokes, clots and heart attacks
  • fibroid growth
  • C-reactive protein (a marker for inflammation)
  • incontinence
  • impaired cognition and dementia
  • insulin resistance
  • abnormal mammograms
  • deaths from lung cancer
  • shielding breast cancer cells from the immune system

None of this is surprising as estrogen is a mitogen, causing cells to divide and multiply, including fat cells. But fat cells are the main non-ovarian site for estrogen production in the body. Breast cancer survivors whose bodies make the least estrogen have the best chance of avoiding the cancer recurring. This applies to all diseases where estrogen is in excess.

Estrogen is an excitatory hormone, which if in excess causes inflammation, water retention and an increase in MMP's (enzymes that break down tissue). MMP's and estrogen are high in cancer and inflammatory diseases such as arthritis, lupus, endometriosis, in fact all autoimmune diseases. Not only that but it's been found that estrogen also shields breast cancer cells from the immune system.

Progesterone suppresses excess estrogen, it's been used successfully in treating some cancers. It has shown beneficial effects for:

  • Alzheimer's
  • Lupus
  • Arthritis
  • Endometriosis
  • Heart disease (it reduces thrombin by 10-15% so preventing clots forming and it prevents lipid peroxidation and atherosclerosis)

Here is a list on what certain HRT’s contain.

  • Vivelle-Dot patch – 0.025, 0.0375, 0.05, 0.075 or 0.1mg estradiol
  • CombiPatch – 0.62mg estradiol, 2.7mg norethindrone acetate or 0.51mg estradiol/4.8mg norethindrone acetate
  • Premarin tablets – 0.3mg, 0.45mg, 0.625mg, 0.9mg and 1.25mg of a mixture of conjugated estrogens, sodium estrone sulphate, sodium equilin salfate, sodim sulphate conjugates, 17CE +- - each dihydroequilin, estradiol derived from pregnant mares’ urine
  • Premarin injections - not very pleasant, contains 25mg conjugated estrogens, 200mg lactose, 12.2mg sodium citrate, 0.2mg simethicone. PH is adjusted with sodium hydroxide or hydrochloric acid
  • Premarin vaginal cream – 0.625mg conjugated estrogens, sodium sulphate conjugates, 17CE  - each of dihydroequilin and estradiol . No liquefying base containing cetyl esters wax, cetyl alcohol, white wax, glyceryl monostearate, propylene glycol monostearate, methyl stearate, benzyl alcohol, sodium lauryl sulphate, glycerine and mineral oil
  • Prempro – 0.3mg (as for Premarin)/1.5mg MPA and 0.45mg (as for Premarin)/1.5mg MPA, 0.625mg (as for Premarin)/2.5mg MPA, 0.625mg (as for Premarin)/5mg MPA

Read this article on HRT and view this video by Dr Sangeeta Pati on Bio-Identical Hormone Replacement Therapy.

 

How to come off HRT and Testosterone Drugs

It is safe to come off the HRT cold turkey, unlike many drugs, but symptoms can come back. It is far gentler on the body is to reduce the HRT etc slowly, always using progesterone whilst doing so.  Progesterone normally counteracts any withdrawal symptoms if this route is followed.  It is best to use progesterone cream for at least a month before attempting to reduce HRT.  Between 100mg/3ml and 200mg/6ml of Natpro per day is needed, use it continuously, there is no need to take a break from use.  A higher dose might be needed if HRT has been used for many years.  If symptoms come back while reducing, increase the amount of progesterone and slow down the HRT reduction. 

Follow these instructions for weaning off HRT, estrogen or progestin:

  • Miss  1 day
  • Take  7 days
  • Miss  1 day
  • Take  6 days 
  • Miss  1 day
  • Take  5 days
  • Miss  1 day
  • Take  4 days
  • Miss  1 days
  • Take  3 days
  • Miss  1 day
  • Take  2 days
  • Miss  1 day
  • Take  1 day

You have now reduced the dose by 50% over 34 days.  Continue missing alternate days until you feel stable, then work back up the above list  i.e.

  • Miss  2 days
  • Take  1 days
  • Miss  3 days
  • Take 1 day
  • And so on .....

This will take about 3 months.  If no symptoms have returned and you feel stable discontinue the HRT.

On a personal note, there is ABSOLUTELY no way that I would ever consider taking the urine of a pregnant mare!! Please think carefully, your health is far too important, there are natural and effective options that you can try!

 

Websites on HRT

 

HRT RESEARCH PAPERS

University of Missouri 2010
Breast Cancer Risk Varies Among Different Progestins Used in Hormone Replacement Therapy, MU Researchers Finds

JAMA. 2010;304(15):1719-1720
Postmenopausal Hormone Therapy and Breast Cancer: An Uncertain Trade-off

Hormone Replacement Therapy (HRT) & Breast Cancer: What You Need to Know - The Trust about Cancer

Medscape October 19, 2010
11-Year WHI Data Show Increase in More Advanced Breast Cancers

Cancer Research October 19, 2010
Tissue-Specific Pathways for Estrogen Regulation of Ovarian Cancer Growth and Metastasis

JAMA. 2010;304(15):1684-1692
Estrogen Plus Progestin and Breast Cancer Incidence and Mortality in Postmenopausal Women

JAMA. 2010;304(15):1719-1720
Postmenopausal Hormone Therapy and Breast Cancer

Medscape October 12, 2010
Hip Fractures Soar When Hormone Therapy Stops

Medscape October 12, 2010
Hormone Therapy Raises CHD Risk in Women With Metabolic Syndrome

Medscape October 13, 2010
Lower Doses of Estrogen in Hormone Therapy Carry Less Cardiovascular Risk

Postmenopausal Hormone Use and the Risk of Nephrolithiasis

Cancer Prevention Research August 10, 2010
Synthetic Progestins Differentially Promote or Prevent 7,12-Dimethylbenz(a)anthracene–Induced Mammary Tumors in Sprague-Dawley Rats

BMJ 2010;340:c2519

Transdermal and oral hormone replacement therapy and the risk of stroke: a nested case-control study

AIM 2010 vol. 152 no. 4 211-217
Coronary Heart Disease in Postmenopausal Recipients of Estrogen Plus Progestin Therapy: Does the Increased Risk Ever Disappear?

ScienceDaily Feb. 19, 2010
Short-Term Heart Disease Risks of Combination Menopausal Hormone Therapy Confirmed

Endocrine-Related Cancer 2009, 16 (1) 85-98
Regression of progestin-accelerated 7,12-dimethylbenz[a]anthracene-induced mammary tumors in Sprague-Dawley rats by p53 reactivation and induction of massive apoptosis: a pilot study

Cochrane Database of Systematic Reviews 2009, Issue 4. Art. No.: CD001405
Oestrogen therapy for urinary incontinence in post-menopausal women

The Lancet, Volume 374, Issue 9697, Pages 1243 - 1251, 10 October 2009
Oestrogen plus progestin and lung cancer in postmenopausal women (Women's Health Initiative trial): a post-hoc analysis of a randomised controlled trial

Hormone Replacement Therapy and Cardiovascular Health in the United States.
Medical Care:May 2009 - Volume 47 - Issue 5 - pp 600-606

The New England Journal of Medicine, Volume 360:573-587 February 5, 2009 Number 6
Breast Cancer after Use of Estrogen plus Progestin in Postmenopausal Women

Cancer Epidemiology, Biomarkers & Prevention March 2008 17; 614
Reproductive Steroid Hormones and Recurrence-Free Survival in Women with a History of Breast Cancer

WebMD Health News March 7, 2008
Estrogen Brings Breast Cancer Back

AIM Vol. 168 No. 4, February 25, 2008
Estrogen Plus Progestin and Breast Cancer Detection by Means of Mammography and Breast Biopsy

ScienceDaily (June 20, 2008)
Complex Changes In The Brain's Vascular System Occur After Menopause

Arch Intern Med. 2008;168(8):861-866.
Postmenopausal Hormone Therapy and Stroke
Role of Time Since Menopause and Age at Initiation of Hormone Therapy

Medscape March 11, 2008
Estrogen Levels Linked to Risk for Breast Cancer Recurrence

From Heart wire - a professional news service of WebMD March 5, 2008
Breast Cancer Risk Remains After Stopping HRT

ScienceDaily (Apr. 9, 2008
Estrogen Therapy Increases Benign Breast Disease Risk, Study Suggests

University of Oxford 19 April 2007
HRT increases incidence of, and deaths from, ovarian cancer

Environ Health Perspect 115:A297-A297 1 June 2007 Molecular Biology: Estrogens Shield Breast Cancer Cells.

NEJM Volume 356:1670-1674 April 19, 2007 Number 16 A sharp decrease in breast cancer incidence in the United States in 2003

The FASEB Journal 2007;21:2285-2293.
Disruption of androgen receptor signaling by synthetic progestins may increase risk of developing breast cancer

BREAST CANCER RESEARCH AND TREATMENT 2006, Volume 101, Number 2, 125-134
Effects of estradiol with micronized progesterone or medroxyprogesterone acetate on risk markers for breast cancer in postmenopausal monkeys

JOURNAL OF CLINICAL ONCOLOGY
VOLUME 24 NUMBER 33 NOVEMBER 20 2006
Recent Declines in Hormone Therapy Utilization and Breast Cancer
Incidence: Clinical and Population-Based Evidence