Effects Of Estrogen Deficiency Research Articles

A Structural Approach to Renal Bone Disease

A Structural Approach to Renal Bone Disease

The effect of estrogen deficiency on rat ganglioside metabolism

The effect of estrogen insufficiency on the formation of gangliosides from precursors is studied. Oophorectomy changes the production of gangliosides in the heart, skeletal muscles, fatty tissue, and pancreas. Estrogen insufficiency is paralleled by decrease of cardiac monosialogangliosides G^j and GM3> skeletal muscle disialogangliosides GDlb and GDla and monosialogangliosides Gmi end Gmj, fatty tissue disialoganglioside GDlb and monosialogangliosides G^] and GM3> and pancreatic monosialoganglioside GMI. The findings indicate that estrogens can contribute to regulation of ganglioside metabolism.

Effect of estrogen deficiency on cancellous and cortical bone structure and strength of the femoral neck in rats.

Eighty mature Sprague-Dawley rats were weight matched before ovariectomy (Ovx) or Sham surgery (Sham). Sham rats had free access to food and water throughout the experiment, whereas Ovx rats were kept on the pair-fed diet. Rats were euthanized at 4, 8, and 12 weeks after surgery, and had received fluorochrome bone markers at 9 and 2 days prior to euthanasia. In addition 10 rats were euthanized at the time of surgery serving as baseline controls. All rats were also scanned for body composition and bone mineral parameters by DEXA before surgery and euthanasia. Left proximal femurs (femoral necks) were used for bone histomorphometry, whereas right femurs were used for in vitro DEXA measurements and mechanical testing. Despite pair-feeding, ovariectomized rats had increased body weights and fat body mass, whereas the percent lean body mass steadily declined throughout the experiment. Mineral density of the whole femur and femoral neck was significantly higher in the Sham rats relative to Ovx animals. Ovariectomy reduced trabecular number and thickness, and increased trabecular separation and bone marrow space at the femoral midneck location. The structure of the remaining trabeculae was dramatically changed toward simpler struts as revealed by nodal analyses. Cortical thickness in Ovx rats was reduced because of the high endocortical resorption, which, in addition to cancellous bone resorption, resulted in fewer endocortico-trabecular connections. Femoral necks obtained from ovariectomized rats had reduced strength and were less stiff relative to controls. Because of the enormous clinical significance of the proximal femur for osteoporosis in humans, and the opportunity for studying bone BMD, mass, structure, and strength at the same skeletal location, the femoral neck appears superior to other skeletal sites routinely used for bone histomorphometry or mechanical testing in the Ovx rat model.

Menopause

1. All women must prepare for their future health as much as they prepare for their future career goals in life. Probably of greatest importance is that this preparation for a continuous state of good health never ends. 2. Not long ago, menopause was considered a short term physiologic event in a woman's life. Now the health care community realizes the short sightedness of this idea, as the effects of estrogen deficiency that begin prior to menopause are lifelong and diverse. 3. One of the most critical health problems facing America today is osteoporosis, a disease causing bones to become thin, fragile, and highly prone to fractures. 4. Prior to menopause, the death and disability rates related to cardiovascular disease in women are relatively low, whereas after menopause, the rates increase sharply. One in 10 American women 45 to 64 years of age have some form of heart disease. Cardiovascular disease kills more women than all forms of cancer combined.

Estrogen replacement therapy in breast cancer survivors

To the Editor. —We wholeheartedly applaud the suggestion by Dr Cobleigh and colleagues1that the role of ERT in the care of postmenopausal women with a history of breast cancer should be defined in a thoughtful and broad-minded manner through carefully designed prospective clinical trials. The realization that omission of the ERT option may no longer be appropriate for all women previously treated for breast cancer has led us to initiate such a prospective study, as the authors point out.2During our interactions with postmenopausal women with prior diagnosis of breast cancer, both within our institution3and in the community, we are impressed by their compelling descriptions of the deleterious effects of estrogen deficiency on their sense of well-being. The principle that no one medical intervention is ever appropriate for all individuals appears intuitively obvious but merits repetition. We would like to caution that neither ERT nor

Persistent bone-sparing effect of interleukin-1 receptor antagonist: A hypothesis on the role of IL-1 in ovariectomy-induced bone loss

The recent finding that treatment with the interleukin-1 (IL-1) inhibitor, interleukin-1 receptor antagonist (IL-1ra) decreases bone loss and bone resorption in ovariectomized rats, strongly suggested that IL-1 mediates, at least in part, the effects of estrogen deficiency on bone resorption. Although in vitro studies have shown that IL-1 activates mature osteoclasts and stimulates osteoclastogenesis, the two main mechanisms by which estrogen deficiency stimulates bone resorption, it is still unclear whether IL-1 mediates both effects of estrogen deficiency in vivo. To investigate this matter, we have examined the changes in bone mineral density (BMD) which occur in ovariectomized rats after completion of 1 month of estrogen or IL-1ra treatment begun at the time of ovariectomy. Ovariectomy caused a marked decreased in BMD which was blocked by 17 beta estradiol and decreased by IL-1ra. Cessation of estrogen therapy was followed by a rapid induction of bone loss, indicating that estrogen blocks the activation and utilization of mature osteoclasts without depleting the bone microenvironment of osteoclast precursors and mature, inactive osteoclasts. In contrast, ovariectomized rats treated with IL-1ra maintained a stable bone density for the first 4 weeks after completion of the treatment. In these rats, bone loss resumed not earlier than 6 weeks after discontinuation of the IL-1ra treatment. Estrogen deficiency was necessary to unveil the bone-sparing effect of IL-1ra because in a control experiment in which rats were treated with IL-1ra for the 4 weeks before ovariectomy, BMD began to decrease immediately after ovariectomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Tamoxifen and Norethisterone: Effects on Plasma Cholesterol and Total Body Calcium Content in the Estrogen-Deficient Rat

It is important that drugs which are used to protect bone from the osteoporotic effects of estrogen deficiency should not affect plasma lipids adversely. Effects of a) norethisterone acetate and b) tamoxifen citrate on plasma cholesterol and on bone conservation in rats with normal plasma 17B-estradiol and in rats made estrogen-deficient with the LHRH agonist, buserelin are reported. Tamoxifen halved total plasma cholesterol (p < 0.01), whereas norethisterone did not lower plasma cholesterol. Furthermore tamoxifen fully protected bone from estrogen-deficiency osteopenia whereas norethisterone conserved bone less well. Reductions in cholesterol elicited by tamoxifen were similar in estrogen-deficient rats and in rats with normal ovarian function. This is the first report in the rat that tamoxifen has lipid-lowering actions. It is suggested the rat may be useful for future investigations of the lipid-lowering mechanisms of tamoxifen.

Estrogen Replacement Therapy: The Benefit Outweighs the Risk

Menopause and the related decline in estrogen result in multiple symptoms including genitourinary atrophy, vasomotor instability, and osteoporosis. The most significant long-term effect of estrogen deficiency is increased risk of cardiovascular disease. Estrogen replacement therapy (ERT) decreases osteoporosis and associated fractures, decreases symptoms associated with menopause, and offers cardioprotection. However, ERT is not without risk because it may lead to increased risk of endometrial cancer if used without progestin, and has been questionably linked to breast cancer. Educating the post-menopausal woman concerning the risks and benefits of ERT is essential to assure compliance. ERT decreases mortality incidence and improves quality of life, and its use for any post-menopausal woman without contraindications is recommended.

Evidence for a Renal Calcium Leak in Postmenopausal Women

We have measured calcium, albumin, globulin, bicarbonate, and anion gap in the plasma; and calcium, sodium, and creatinine in the urine, in 115 premenopausal and 140 postmenopausal normal women after an overnight fast, and calculated the calcium fractions in the plasma and the calcium/and sodium/creatinine ratios in the urine. The total ultrafiltrable calcium was significantly higher in the postmenopausal group, mainly due to their higher complexed calcium fraction, due in turn to their higher bicarbonate and anion gap concentrations. Urinary calcium was also significantly higher in the postmenopausal group even after correcting for sodium. After matching for total calcium and each of the calcium fractions in turn, the urinary calcium remained significantly higher in the post- than in the premenopausal sets even after correction for sodium. The implication is that the rise in urinary calcium at the menopause is due to reduced tubular reabsorption of calcium rather than to an increase in filtered load. We suggest that estrogens promote tubular reabsorption of calcium and that the rise in bone resorption at the menopause could be accounted for, at least in part, by the effect of estrogen deficiency on the kidney.

Decreased osteoinductive potential of bone matrix from ovariectomized rats.

The effect of estrogen deficiency on matrix-induced bone formation was investigated. Female rats were ovariectomized and given demineralized bone matrix (DBM) intramuscularly 3 weeks before termination. The DBM was taken from previously ovariectomized and from sham-operated on rats. The animals were killed at various times after ovariectomy (6-27 weeks). Implants were processed undemineralized for histologic and biochemical studies. Normal DBM implanted in ovariectomized or normal rats induced extensive bone formation 6 weeks postovariectomy. The amount of newly formed bone decreased with the age of host rats. Bone matrix taken from ovariectomized rats was incompletely resorbed in both ovariectomized and normal hosts, therefore reducing the extent of osteogenesis and bone-marrow formation. Instead, chondrogenesis was intensive, but delayed. The calcium, magnesium, and zinc contents were decreased in implants taken from ovariectomized rats when compared with implants taken from normal animals. Normal osteoinduction with DBM taken from normal rats and implanted in ovariectomized rats and the absence of osteogenesis with DBM taken from ovariectomized rats indicate that an estrogen-deficient environment is not crucial for altered matrix-induced endochondral bone formation in ovariectomized rats. An altered composition of matrix from ovariectomized rats and a subsequent abnormality in the cell-matrix interaction should be considered responsible.

Effects of estrogen deficiency on the growth of tissue into porous titanium implants.

The effect of systemic deficiency of estrogen on the growth of tissue into porous titanium-fiber implants was studied in ovariectomized Beagle dogs. Five dogs were ovariectomized and five dogs had a sham operation. After waiting four months to allow the levels of circulating estrogen to decline, a titanium-alloy implant that contained four surface pads of titanium-alloy mesh was implanted in the proximal part of the humerus of each dog bilaterally. Two months later, the implants were harvested and subjected to a mechanical push-out test and quantitative histological study. The push-out strength of the implants from the ovariectomized dogs was 31 per cent less than in the control animals. Ovariectomy caused no difference in the amount of ingrowth of bone but resulted in a significant increase in the amount of fibrous connective tissue within the porous pads. The presence of this fibrous tissue appeared to have an important effect on bone-implant fixation: in the control dogs, strength correlated positively with ingrowth of bone and negatively with ingrowth of fibrous tissue, whereas in the ovariectomized dogs, strength correlated positively with ingrowth of fibrous tissue and not at all with ingrowth of bone.

Effects of estrogen deficiency on the mechanical properties of the Beagle skeleton

Effects of estrogen deficiency on the mechanical properties of the Beagle skeleton

Effects of estrogen deficiency in women castrated when young.

In earlier studies on the effects of castration, most of the women had been operated on late in the reproductive period of life. In the present material all the 142 women had been oophorectomized between the ages of 15 and 30 years because of advanced salpingitis. Not only the tubes but also the ovaries had been radically removed. The series was analyzed in respect of causes of death, survival, morbidity, osteoporosis and hormonal state. Complete oophorectomy was found to be followed by (i) a significant increase in the frequency of coronary heart diseases; (ii) an increase in serum cholesterol and triglyceride levels, most significantly in those aged below 60-65 years; (iii) an increase incidence of fractures; (iv) in increased frequency of nervous disorders of psychological rather than endocrinological origin.