HRT - HORMONE REPLACEMENT THERAPY

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

Since the 1950s, synthetic estrogen and, more recently, bio-identical estrogen have been prescribed as hormone replacement therapy (HRT) for women to ease certain menopausal symptoms. By the mid-1960s, it was widely marketed as a miracle solution for menopausal women, with slogans promoting the idea of remaining "Feminine Forever," a phrase popularized by Dr. Robert Wilson in his book.

Wyeth Ayerst created the first conjugated estrogen known as Premarin, an abbreviation for 'Pregnant Mare's Urine'. As the name indicates, it is derived from the urine of pregnant mares. These mares, reportedly numbering as many as 80,000, are confined in stalls for six months each year and are given minimal water to intensify the concentration of the urine, which is collected in bags positioned beneath their tails. The urine undergoes processing to extract various hormones, with only 40% being human hormones; the remaining potent 60% comprises equine hormones. It's not surprising that many women do not fare well on this treatment. By 2003, around 15% of women in the US were using it, but those who tried it tended to stay on it for an average of just one year. Thankfully, that number has significantly declined since then.

Initially, treatment involved administering only estrogen; however, the 1970s witnessed a troubling rise in cases of endometrial cancer. A 1976 study published in the New England Journal of Medicine (NEJM) reported that the increase exceeded 10% in certain regions. For middle-aged women, this rise was even more pronounced, ranging from 40% to as much as 150%.

As early as 1976, an increase in breast cancer cases was observed, yet estrogen continues to be recommended for managing menopause symptoms. A Medline article referenced a study that monitored 1,891 women over a span of 12 years. While researchers anticipated that 39.1 women would develop cancer during this period, the actual number was 49, resulting in a relative risk of 1.3%. This figure climbed to 2.0% after 15 years. As any woman who has experienced cancer can attest, the potential benefits do not outweigh the associated risks.

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Thus, hormone replacement therapy (HRT) was established. To mitigate the risk of endometrial cancer, synthetic progesterone, often referred to as 'progestin' or 'progestogen', was incorporated with estrogen. Amidst the enthusiasm surrounding a potential remedy for the increasing cases of endometrial cancer, the simultaneous rise in breast cancer was regrettably overlooked.

In July 2002, the Women's Health Initiative (WHI) was halted prematurely after findings indicated that hormone replacement therapy (HRT) elevated the risks of heart disease—specifically stroke, heart attack, and blood clots—as well as breast cancer. Consequently, approximately 50% of users discontinued the medication.

The encouraging news is that in 2003, breast cancer rates experienced a 7% decline overall, with a notable 12% decrease among women aged 50 to 69. This reduction is particularly intriguing, especially given that breast cancer rates had escalated by 30% from 1975 to 2000. Additionally, the WHI study revealed that both estrogen alone and its combination with progestin raised the likelihood of urinary incontinence.

From 1996 to 2001, The Million Women Study in the UK discovered that the risks associated with oral, transdermal, and implanted estrogen-only treatments were significantly heightened, but even more so for estrogen-progestagen. This elevated risk pertained to breast, ovarian, and endometrial cancers.

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

In 2003, researchers at the University of Wisconsin discovered that the use of HRT was linked to a 7% higher risk of endometrial cancer for each year it was utilized.

An intriguing study carried out in Brazil in 2004 revealed that transdermal estrogen combined with 100mg of vaginal progesterone did not elevate the risk of hypertension and did not influence levels of thrombin, renin, or aldosterone.

A comparable study conducted in France in 2004 discovered that the risk associated with HRT containing synthetic progestins was significantly higher than that of HRT using micronized progesterone.

C-reactive protein (CRP) serves as a marker for inflammation and is considered a risk factor for cardiovascular disease. A 2004 study conducted in Italy revealed a 66% increase in risk among estrogen-only users and a staggering 112% increase for individuals undergoing combined hormone replacement therapy.

The 2005 Nurses' Health Study identified that individuals using hormone replacement therapy (HRT) exhibited statistically significant elevations in estradiol, free estradiol, and testosterone levels compared to non-users. The findings indicated a correlation between plasma sex hormone concentrations and breast cancer risk among HRT users. Additionally, the study uncovered a 78% increased likelihood of developing urinary incontinence.

Additional findings from the WHI revealed that after five years of HRT (Prempro), cognitive function declined, and the risk of developing dementia was doubled.

By 2007, research indicated that the combination of estrogen and medroxyprogesterone acetate led to insulin resistance.

A subsequent study of the WHI conducted in 2008 revealed that women who had undergone HRT continued to face an elevated risk of breast cancer for three years following cessation. Moreover, those who used HRT for one year experienced a 4% heightened risk of abnormal mammograms, which increased to 11% after five years. This situation compromises the findings, resulting in unnecessary biopsies.

In 2009, a study was carried out in Denmark involving women aged 50 to 79, examining national registers from 1995 to 2005. The researchers concluded, "Regardless of the duration of use, formulation, estrogen dose, regimen, progestin type, or route of administration, hormone therapy was linked to a heightened risk of ovarian cancer."

In 2009, a study published in The Lancet revealed that while hormone replacement therapy (HRT) did not elevate the risk of lung cancer, it was associated with a higher number of fatalities.

A 2010 review by the Cochrane Incontinence Group determined that both conjugated equine estrogen and a combination of estrogen and progestogen significantly exacerbated 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 unexpected, as estrogen acts as a mitogen, stimulating the division and proliferation of cells, including fat cells. However, fat cells serve as the primary non-ovarian source of estrogen production in the body. Breast cancer survivors with lower levels of estrogen production have the greatest likelihood of preventing cancer recurrence. This principle holds true for all conditions characterized by excess estrogen.

Estrogen is an excitatory hormone, and when present in excess, it leads to inflammation, water retention, and an increase in MMPs (enzymes that degrade tissue). Elevated levels of MMPs and estrogen are commonly associated with cancer and inflammatory conditions like arthritis, lupus, and endometriosis, as well as with all autoimmune diseases. Moreover, research indicates that estrogen can protect breast cancer cells from the immune system's response.

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 generally safe to discontinue HRT abruptly, unlike many other medications, though symptoms may re-emerge.

It is much gentler on the body to gradually reduce HRT, using progesterone during the process. Progesterone typically alleviates any withdrawal symptoms when this method is employed. It's advisable to apply progesterone cream for at least a month before initiating the HRT reduction. An amount between 100mg/3ml and 200mg/6ml of Natpro daily is recommended, and it should be used continuously—there's no need for breaks. A higher dosage may be necessary if HRT has been administered for many years. If symptoms reappear during the reduction, increase the progesterone dosage and slow down the tapering of HRT.

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 process will take approximately 3 months. If symptoms do not return and you feel stable, you may discontinue the HRT.

On a personal level, there is NO WAY that I would ever entertain the idea of utilizing the urine of a pregnant mare! Please take a moment to reflect—your health is far too valuable. There are natural and effective alternatives that you can explore!

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



The Haunting of Medical Journals: How Ghostwriting Sold “HRT”

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

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
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

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

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

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

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

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