These cytokines increase bone resorption (breakdown) mainly by increasing the amount of pre-osteoclasts in bone marrow. RANKL stimulates all aspects of osteoclast function and allows for a decrease in apoptosis of osteoclasts. Apoptosis is programmed cell death. This is a process common to regenerating tissues. Old tissue is removed to allow for renewed, fresh tissue.

Prostaglandin E2 increases RANKL and decreases osteoprotegerin*. Post menopausal estrogen loss increases osteoclast recruitment and the generation of new bone units that undergo a remodeling cycle, and extends the bone resorption phase by reducing osteoclast apoptosis (cell death).

Simultaneously, diminished estrogen down regulates (lessens) the local production of osteoprotegerin, insulin like growth factors I, II and transforming growth factor beta. Osteoprotegerin* is a protein secreted by osteoblasts that inhibits the production and activity of osteoclasts. Osteoprotegerin neutralizes RANKL.

Diminished estrogen suppresses the survival of osteocytes and osteoblasts and impairs their response to mechanical stimuli, the detection of micro damage and the repair of bone.

Estrogen replacement modifies the local production of the above mentioned cytokines and growth factors, decreases the formation of osteoclasts and extends the osteoblast and osteocyte lifespan. The bone building effects of estrogen include an increased osteoblast proliferation, differentiation, function and an extended osteoblast lifespan.

Research confirms a 50% reduction in fracture incidence in women who use estrogen replacement, providing they use estrogen promptly and continuously. Women who start using estrogen replacement at the onset of menopause can maintain bone at its onset level. Women who start using estrogen replacement a few years later maintain bone at a lower level. When postmenopausal women stop estrogen replacement bone begins to rapidly lose its mass again. Estrogen replacement is indicated for the prevention of osteoporotic fracture, not for the treatment of osteoporotic fracture.

Advances in the dosage and delivery of hormone replacement have brought significant options for women to achieve vibrant health during the menopausal transition and the post menopausal years. Transdermal estrogen patches the size of a postage stamp help provide personalized treatment with estradiol dosage options of 0.025 mg/day, 0.0375mg/day, 0.50mg/day, 0.075mg/day, or 0.1mg/day. Transdermal estrogen patches are replaced bi weekly or weekly and are often soy/plant derived estrogen.

With a transdermal patch, estrogen is absorbed through the skin directly into the bloodstream. This is similar to how the estrogen produced by the ovaries flowed to estrogen sensitive tissues before menopause. Because the estrogen from the patch is absorbed through the skin directly into the bloodstream, it avoids going through the stomach, intestines and the liver. As such an estrogen patch provides a much smaller amount of hormone than estrogen pills.

The transdermal estrogen replacement patch does not generate a negative effect on lipids (cholesterol) or cause an increased risk of gallbladder disease.

Low dose patches that release 0.025 mg/day of estrogen and even ultra low dose patches containing 14 mcg/day of estrogen prevent bone loss in postmenopausal women. This small increase in estrogen renews the osteoblast and osteoclast self repair of bone that was regulated before menopause.

The evolution of hormone replacement therapy now offers products that contain lower doses of both estrogen and progesterone and combination products that contain newer progestins that generate specific benefits.

One example is a combination product containing estradiol and a unique progestin: drospirenone. The combination of estradiol/drospirenone offers peri menopausal women a therapeutic option to help ease moderate to severe vasomotor symptoms, such as hot flashes, night sweats and vaginal atrophy/dryness while protecting bone mineral density. Aldosterone is a sodium (salt) regulating hormone. Drospironone demonstrates anti-aldosterone activity which results in less fluid retention and favorable effects on blood pressure.

The estrogen patch, the estrogen pill, and combination estrogen and progestin hormone replacement each have different effects on coronary risk factors. The interaction between hormone replacement, routes of administration and coronary risk factors is presented in the overview How Estrogen effects Cholesterol Metabolism.