• The Science Behind Bio-Identical Hormone Therapy

    Studies have shown that balanced hormones are necessary for good health and disease prevention for both men and women as we age.

    Scientists analyzing research

Research & Journal Articles

  • American Association of Clinical Endocrinologists & American College of Endocrinology Position Statement on the Association of Testosterone and Cardiovascular Risk
    • Concluded that testosterone therapy can provide significant benefits for hypogonadal men
    • There is no compelling evidence that testosterone therapy increases cardiovascular risk
    Read More
  • Association Between Serum Testosterone Concentration and Carotid Atherosclerosis in Men With Type 2 Diabetes
    • There is evidence to suggest that low concentrations of testosterone are associated with an increased risk of cardiovascular disease in men
    • Serum F-testosterone concentration is inversely associated with carotid atherosclerosis
    Read More
  • Cache County Study
    • Observational study of 70,000+ inhabitants of Cache County (NE Utah)
    • 1995-2013 Looked at HRT and Alzheimer’s
    • HRT beneficial but timing and duration important variables
    • Cache county study – HRT started late increased risk of Alzheimer’s but starting early showed a decrease risk in Alzheimer’s
    Read More
  • Concerns About Testosterone Replacement Safety Evolve
    • There is fear that we are going to stimulate an occult prostate cancer.
    • The bulk of existing data discounts that notion
    • (N. Engl. J. Med. 2004;350:482-92) That rate of cancer in treated men is identical to rates in untreated men.
    • None of 12 longitudinal population-based studies such as the Baltimore Longitudinal Study of Aging or the Physicians’ Health Study found any increased risk for prostate cancer in men with higher testosterone levels compared with men with lower levels.
    Read More
  • Coronary Risk Factors for Atherosclerosis
    • 1997-2001 study looked at 200 participants with CHD vs. 255 without CHD
    • HRT may be beneficial and not associated with increased risk for CHD. Even females who started HRT later in life had a decreased cardiovascular risk
    • This is a German Study
    • Oral E2 showed no increased risk of VTE/PE
    • This study showed that decreased insulin resistance with HRT especially oral and oral E2 is safe
    Read More
  • Danish Osteoporosis Prevention Study
    • HRT and Osteoporosis, looking at Oral E2 – + Progestin vs just oral E2
    • 1990-2003 – 2016 perimenopausal women. An additional observation was a reduction in CVD with HRT
    • The subgroup was 502 for HRT and 504 for placebo
    • Important to note that this group took E2, while Premarin was used in the WHI
    • This was the longest oral E2 study >10 years. Oral E2 is safe with no increase in heart disease or DVT’s and there was a decreased risk of CVA and breast cancer
    • There was no increased risk of VTE/PE with oral E2
    • Oral E2 is safe
    Read More
  • Early vs Late Intervention Trial with E2
    • 2005-2008 – 643 post-menopausal women
    • Proves the timing of HRT in relation to menopause is important in preventing
      atherosclerosis. Checked for carotid intima media thickness (CIMT) and CT coronary
      calcium scores
    • Used 1 mg of oral E2 vs placebo
    • Early is better than late for CIMT, but null results for CT calcium scores
    • Timing of HRT since menopause defined as <6 years and >/= 10 years
    • Oral E2 is safe
    Read More
  • Endogenous sex hormone levels and cognitive function in aging men: is there an optimal level?
    • Higher testosterone (T) levels are associated with better cognitive performance in the oldest age category.
    Read More
  • Estrogen in the Prevention of Atherosclerosis Trial
    • 1994-1998 – 222 females
    • Measure distal common carotid artery intima media thickness on E2 one mg/day +/-
    • Pravastatin if LDL > 160
    • E2 decreases CIMT / oral E2 is safe
    • No increased risk VTE/PE with oral E2
    Read More
  • Estrogen and Thromboembolism Risk
    • 1999-2005 – 253 with VTE vs 597 without VTE (venous thromboembolism)
    • Case control French Study of Oral vs Transdermal E2 on VTE (mainly 17 B-estradiol)
    • Association with increased BMI (body mass index)
    • This was an observational study
    • Oral dose was 1.5 mg/day but transdermal was 50 micrograms/day
    • P4 does not increase clotting
    Read More
  • The European Prospective Investigation Into Cancer and Nutrition
    • 1993 – 2009+ (ongoing study)
    • Approximately 521,000 participants and followed for 15 years
    • Looked at diet, nutritional status, lifestyle and environmental factors vs cancer/chronic diseases
    • In men, testosterone levels inversely related to CVD mortality, low testosterone predictive for those with high risk of CVD
    • EPIC – E3N (A French cohort study on cancer risk factors) P4 is safer than Provera for Breast Cancer
    Read More
  • Heart and Estrogen/Progestin Replacement Study
    • HRT vs Heart attacks/CVD
    • 1992-2001 – 2763 postmenopausal females (1380 HRT and 1383 placebo) treated for 4.1 years.
    • No benefit* against heart attacks/CVD (but results similar to WHI year one vs remainder of years showing early harm and later benefit). Funded by Wyeth-Ayerst Labs, makers of PremPro
    • Do not recommend HRT for secondary prevention
    • *First RCT to look at HRT and CVD. Had to have pre-existing CAD
    • *Possible adverse effects of Provera and also estrogen alone. See PEPI trial. Emphasize importance of basing treatment policies on RCT (randomized controlled trials) vs observational studies
    • HERS I – E2 and CHD, same curve as WHI
    • CEE – clotting RR 1.4 in year 1. Don’t recommend ERT despite RR 0.6 after 5 years, CVA risk not increased
    • Only 2.7 years vs 4 year follow up of 2321 females (1156 HRT and 1165 placebo)
    • Absence of overall long term benefit of HRT
    Read More
  • Invecchiare in Chianti (aging in the Chianti area)
    • 1998-2000 – 1155 patients located in Tuscany, Italy. Follow-up 2007-2009
    • Studied various physiological subsystems important for mobility and chronic disease states
    • Antioxidants / physical performance / elderly = >/=65 y/o
    • Increase in total urinary polyphenols* associated with decreased physical performance decline
    • *Mediterranean diet which is high in fruits and vegetables
    • Relationship between low levels of anabolic hormones and 6-year mortality in older men
    • In this study high E2 levels associated with metabolic syndrome
    Read More
  • Justification for the Use of Statin in Prevention: An intervention Trial Evaluating Rosuvastatin (JUPITER): Rationale and pre-specified analyses
    • 2003 – 2006 – 17,802 participants
    • Is Rosuvastatin effective in primary CVD prevention, namely normal LDL cholesterol and elevated hs-CRP
    • Trial was stopped early due to the “44% reduction in composite end point in Crestor usage”
    • Analysis of the all-cause mortality curves shows that the curves were actually converging when the trial ended, suggesting that the borderline significant difference between groups may have disappeared had they had a longer follow-up
    • Funded by AstraZeneca (manufacturers of Crestor) who also collected the data and monitored the study sites.
    • Nine of the 14 authors had financial had financial ties to AstraZeneca and the lead investigator held a patent for the hs-CRP test.
    Read More
  • Kronos Early Estrogen Prevention Study
    • 2005–2012 – 727 Women
    • 727 women into 3 groups
      • Group 1 – low dose oral premarin and prometrium
      • Group 2 – transdermal E2 and prometrium
      • Group 3 – placebo
    • As expected, oral premarin improved lipids while transdermal E2 was neutral
    • Note: start HRT early, look at CIMT/coronary calcium scores
    Read More
  • Nurses’ Health Study (3 parts)
    • 1976-2004+
    • Lifestyle / HRT vs overall health. Only married nurses could participate in Part 1
    • NHS Part 1 – 121,700 nurses
    • NHS Part 2 – 116,430 new nurses (1989)
    • NHS Part III – ???? (2010)
    • Very wide sweeping observational study. Discussed in detail in BHRT Workshops I – IV
    • Hormone levels and Breast Cancer
      • Estrone sulfate RR 1.37
      • SHBG RR 0.82
    • Unopposed HRT and breast cancer 5.0 – 9.9 years RR 0.87
    • >.=20 ears unopposed HRT RR 1.42
    • Prempro and Breast Cancer RR 1.66
    • E2 / post-menopausal female / CHD in the NHS RR 0.55
    • NHS: 50% decrease CVD/CVA/with HRT
    Read More
  • Postmenopausal Estrogen/Progestin Interventions Trial
    • 1987-2000 596 – looked at endometrium, 875 postmenopausal women given Premarin +/- Provera/Progesterone
    • This study looked at estrogen, lipids and fibrinogen. Favorable study mainly unopposed estrogen, increased risk of endometrial hyperplasia
    • 3 year study on the endometrium
    • 596 women divided as follows:
      • Group 1 – CEE only
      • Group 2 – CEE (Premarin) + 10mg MPA (medroxyprogesterone)
      • Group 3 – CEE + 2.5 mg MPA
      • Group 4 – CEE + P4 (progesterone)
    • Looked only at endometrium: CEE alone is bad
    • CEE + P4/MPA protects endometrium
    • As expected, unopposed CEE leads to increased endometrial hyperplasia
    • P4 protects against endometrial hyperplasia
    • Oral E2 reduces CVD
    • Prempro worse CV outcome than with Premarin and P4
    Read More
  • Risk of Venous Thromboembolism in Men Receiving Testosterone Therapy
    To examine the risk of venous thromboembolism (VTE) associated with exposure to testosterone
    therapy in middle-aged and older men.

    Having filled a prescription for testosterone therapy was not associated with an increased risk
    of VTE in commercially insured middle-aged and older men. These findings may provide clinically relevant
    information about the benefit-risk assessment for men with testosterone deficiency considering treatment.

    Read More
  • The Rotterdam Study
    • 1990 – ongoing
    • Three cohorts – RS-1, RS-11, RS-III, RS-IV
    • 14926+ inhabitants of Ommoord (Rotterdam) observed for chronic conditions
    • Findings include a relationship between subclinical hypothyroidism and CVD
    • Also Vitamin D and metabolic syndrome
    • Independent inverse association between testosterone levels and aortic atherosclerosis
    • One observation talks about dietary patterns, BMD and hip structure in the elderly
    Read More
  • Women’s Estrogen for Stroke Trial
    • 1993-1999 461 females (231 E2 and 230 placebo)
    • HRT vs. secondary prevention of CVA (cerebrovascular accident)
    • Followed for 3 years on one mg of oral E2.
      • Results showed reduction in AD (in females with normal cognition at baseline, E2 is beneficial
      • No change in VTE or breast cancer risk
    • E2 showed no increase rates of VTE, breast cancer or CVA’s
    • Oral E2 is safe
    • No increased rates of VTE or breast cancer
    Read More
  • Women’s Health Initiative
    • Study of postmenopausal women
    • There were 2 major parts to the study: A randomized clinical trial and an observational study
    • The entire WHI had 161,808 postmenopausal women
    • 1991-2004 68,132 in the clinical trial
    • 1993-2003 27,347 women in WHI hormone therapy
    • 1998-2010 93,676 women in the observational study
    • Multitude of conclusions to be reviewed and discussed in BHRT Parts I – IV
    Read More