A compendium of research articles and their relevancy to natural hormone replacement therapy:

Reduced breast cancer incidence in women treated with subcutaneous testosterone, or testosterone with anastrozoel: A prospective, observational study

Continuous T and T + A, delivered as a subcutaneous implant, seems to represent safe and effective therapy in treating hormonal symptoms in both pre and postmenopausal women. In this study, safety is verified by the significant decline in breast cancer incidence. We demonstrated that subcutaneous T, and subsequently, T + A, has a protective effect in the breast, and prevented cancer occurrence in some cases. Our findings are consistent with the known favorable biological effect of T on the breast tissue via the AR, as well as data from previously reported preclinical and clinical studies. Our results refute the ‘cause and effect interpretation’ of epidemiological studies demonstrating an association of endogenous testosterone levels with breast cancer. Further studies should be done on subcutaneous T, and the combination of T + A, for the possible prevention and therapy of breast cancer.

Hormone replacement therapy in the geriatric patient: current state of the evidence and questions for the future. Estrogen, progesterone, testosterone, and thyroid hormone augmentation in geriatric clinical practice: part 1.

Successful Aging – Clinics in Geriatric Medicine

Estrogen Actions in the Brain and the Basis for Differential Action in Men and Women: A Case for Sex-Specific Medicines

In summary, although many questions still need to be resolved, there is substantial evidence for the therapeutic benefits of estrogens in the brain, but current evidence suggests that beneficial effects found in females are not directly transferable to males. This is due to sex dimorphisms in the brain, which, contrary to early views, seem to be the norm rather than the exception. Together, these are powerful arguments that highlight the need for a sex-specific approach to novel hormone-dependent therapies.

Breast cancer incidence in postmenopausal women using testosterone in addition to usual hormone therapy

These observations suggest that the addition of testosterone to conventional hormone therapy for postmenopausal women does not increase and may indeed reduce the hormone therapy-associated breast cancer risk-thereby returning the incidence to the normal rates observed in the general, untreated population.

Unequal risks for breast cancer associated with different hormone replacement therapies: results from the E3N cohort study

Findings suggest that the choice of the progestagen component in combined HRT is of importance regarding breast cancer risk; it could be preferable to use progesterone or dydrogesterone

Additive protective effects of estrogen and androgen treatment on trabecular bone in ovariectomized rats.

These findings show that combined estrogen and androgen treatment results in additive protective effects on trabecular bone in OVX rats. Our data suggest that a combined treatment with selective ER and AR modulators might be beneficial in the treatment of osteoporosis.

Testosterone patch increases sexual activity and desire in surgically menopausal women with hypoactive sexual desire disorder.

In the Intimate SM 1 study, the testosterone patch improved sexual function and decreased distress in surgically menopausal women with HSDD and was well tolerated in this trial.

Testosterone enhances estradiol’s effects on postmenopausal bone density and sexuality.

We concluded that in postmenopausal women, treatment with combined estradiol and testosterone implants was more effective in increasing bone mineral density in the hip and lumbar spine than estradiol implants alone. Significantly greater improvement in sexuality was observed with combined therapy, verifying the therapeutic value of testosterone implants for diminished libido in postmenopausal women. The favourable estrogenic effects on lipids were preserved in women treated with T, in association with beneficial changes in body composition.

Effects of estradiol with and without testosterone on body composition and relationships with lipids in postmenopausal women.

Estrogen replacement has effects on body fat distribution in postmenopausal women that are associated with improved lipid parameters. Addition ofparenteral testosterone does not negate the favorable effects of estrogen on LDL cholesterol levels but may attenuate the reduction in centralized body fat achieved with E implants.

Vascular Effects of Estrogenic Menopausal Hormone Therapy

A very thorough approach to the facts surrounding Menopausal Hormone Therapy (MHT). A balanced picture of the benefits and risk factors.

Osteoarthritis associated with estrogen deficiency

Progressive structural and functional changes on articular structures commence at early menopause and persist post-menopause, leading to an increase in the prevalence of OA in the latter population and representing a big impact on health costs worldwide. Both experimental and observational evidence support a relevant role for estrogens in the homeostasis of joint tissues and, hence, in the health status of joints. Indeed, estrogens influence their metabolism at many crucial levels and through several complex molecular mechanisms. These effects of estrogens at joints are either significantly dampened or lost as a result of postmenopausal ovary insufficiency.

Protective actions of sex steroid hormones in Alzheimer’s disease

An interesting compilation of information relating to Alzheimer’s the impact estrogen and testosterone may have in protecting against the disease.

Paradoxical Clinical Effect of Estrogen on Breast Cancer Risk: A “New” Biology of Estrogen-induced Apoptosis

An interesting explanation of the “paradoxical” results of the WHI where administration of estrogen replacement therapy decreased the incidence of breast cancer.

Estrogen Replacement Therapy

A conclusion from Dr. Robert Marcus, M.D.

The risks and benefits of long-term estrogen replacement therapy.

Estrogen replacement therapy (ERT) for postmenopausal women greatly reduces the risk of osteoporotic fractures, but carries an increased risk of endometrial cancer. This risk can be reduced by the addition of progestin, which does not interfere with the osteoporotic benefit of estrogen. Although long-term use data are few, there is presently little evidence for an increase or decrease in breast cancer risk associated with estrogen by itself (unopposed estrogen), or estrogen plus progestin. In contrast, a large body of evidence suggests that unopposed estrogen significantly reduces the risk of cardiovascular disease; there is no evidence that this benefit will persist when a progestin is added. The preferred method of estrogen replacement therapy, to prevent osteoporosis in a postmenopausal woman with an intact uterus, should be chosen with these different risks and benefits in mind.

The 2012 Hormone Therapy Position Statement of The North American Menopause Society

Current evidence supports the use of HT for perimenopausal and postmenopausal women when the balance of potential benefits and risks is favorable for the individual woman. This position statement reviews the effects of ET and EPT on many aspects of women’s health and recognizes the greater safety profile associated with ET.

Longitudinal effects of aging on serum total and free testosterone levels in healthy men. Baltimore Longitudinal Study of Aging.

Using total T criteria, incidence of hypogonadal T levels increased to about 20% of men over 60, 30% over 70 and 50% over 80 yr of age, and even greater percentages when free T index criteria were employed.

These issues bear on the potential use of T replacement in aging men, because aging and hypogonadism have, in common, reduced bone and lean body mass and muscle strength and increased total and abdominal fat.

Age trends in the level of serum testosterone and other hormones in middle-aged men: longitudinal results from the Massachusetts male aging study.

Total T declined cross-sectionally at 0.8%/yr of age within the follow-up data, whereas both free and albumin-bound T declined at about 2%/yr, all significantly more steeply than within the baseline data.

Effects of testosterone on coronary vasomotor regulation in men with coronary heart disease.

Short-term intracoronary administration of testosterone, at physiological concentrations, induces coronary artery dilatation and increases coronary blood flow in men with established coronary artery disease.

Testosterone replacement therapy improves insulin resistance, glycaemic control, visceral adiposity and hypercholesterolaemia in hypogonadal men with type 2 diabetes.

Testosterone replacement therapy reduces insulin resistance and improves glycaemic control in hypogonadal men with type 2 diabetes. Improvements in glycaemic control, insulin resistance, cholesterol and visceral adiposity together represent an overall reduction in cardiovascular risk.

Bioavailable testosterone in men with rheumatoid arthritis-high frequency of hypogonadism.

Men with RA had lower levels of bioavailable T and a large proportion were considered hypogonadal. The low levels of LH suggested a central origin of the relative hypoandrogenicity.

Protective actions of sex steroid hormones in Alzheimer’s disease

An interesting compilation of information relating to Alzheimer’s the impact estrogen and testosterone may have in protecting against the disease.