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Life Extension Magazine

LE Magazine June 2003

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Ovarian aging and the menopausal transition.

The underlying cause of the menopausal transition is a dwindling supply of FSH-responsive follicles available for ovulation. Additional factors may include dysregulation of existing follicles and concurrent follicle and oocyte deficits that may be strictly anatomic or consequences of the hormonal milieu. In the early transition, menstrual irregularity is infrequent but cycle length shortens by one to four days. Estrogen production may be overall elevated, even in ovulatory cycles. As anovulatory cycles become more common, and amenorrhoea of greater duration, evidence of impaired hypothalamic-pituitary function is present. Estradiol has been implicated as an agent responsible for the impaired positive feedback response. A model of the early menopausal transition suggests that the loss of FSH restraint by the inhibins, due to a critically diminished follicle pool, is the early event that precedes overt follicle failure and may initiate intervals of hyperoestrogenaemia. The hormonal fluctuations in the early and late menopausal transition may account for some of the signs and symptoms seen during these phases.

Best Pract Res Clin Obstet Gynaecol 2002 Jun;16(3):263-76

Progesterone receptor activation: An alternative to SERMs in breast cancer.

Data regarding the effects of progesterone and a progestagen on human normal breast epithelial cell proliferation and apoptosis are presented here. In postmenopausal women, adding progesterone to percutaneously administrated estradiol significantly reduces the proliferation induced by estradiol. In vitro and in premenopausal women, stopping the administration of nomegestrol acetate triggers a peak of apoptosis. Fibro-adenoma and cancerous cells do not show this regulation of apoptosis. Progesterone seems to be important in normal breast homeostasis.

Eur J Cancer 2000 Sep;36 Suppl 4:S90-1

Menses and breast cancer: does timing of mammographically directed core biopsy affect outcome?

BACKGROUND AND OBJECTIVES: Studies have shown molecular, genetic and cellular changes in breast cancer during the menstrual cycle. Changes in proliferative and metastatic potential of breast cancer cells during menses could explain improved survival when tumors are surgically removed in the luteal phase. This study examined if timing of mammography/core biopsy (MAM-CB) also affected breast cancer prognosis (histological tumor grade). METHODS: Eighty-five premenopausal women undergoing MAM-CB at one clinic between March 1995 and February 1998 were retrospectively studied. All patients had Stage I or II breast cancer surgically treated. Patients were grouped by phase of menses at MAM-CB: follicular (F, Days 0-14) or luteal (L, Days 15-35). Groups were comparable in age, menarche, family history, nulliparity, breastfeeding and total percentage of clinically palpable tumors. Pathological characteristics of the tumors (tumor size, tumor type, estrogen and progesterone receptor status, axillary lymph node status, the presence of lymphatic or vascular invasion and extranodal metastasis) was also comparable across the two groups. RESULTS: Low-grade tumors were more frequent in the MAM-CB group L, whereas high-grade tumors were more common in the MAM-CB group F (P = 0.002, chi2(4) = 17.06). CONCLUSIONS: Timing of MAM-CB in relation to menses may be a factor influencing breast cancer outcome. Future studies examining the effect of menses on the outcome of breast cancer should consider the potential effect of the timing of MAM-CB.

J Surg Oncol 2000 Jul;74(3):232-6

Timing of surgery during the menstrual cycle and prognosis of breast cancer.

There are conflicting reports on the differential effect of surgery performed during the two phases of the menstrual cycle, namely, follicular and luteal and prognosis of operable breast cancer. A statistical meta-analysis of the published evidence suggests a modest survival benefit of 15+/-4% when the operation is performed during the luteal phase. Further research in this area might provide a novel avenue to understand the natural history of breast cancer. A spin off from these studies might be the understanding of the importance of events that occur at the time of surgery in determining long term prognosis.

J Biosci 2000 Mar;25(1):113-20

Osteoarthritis: diagnosis and therapeutic considerations.

Osteoarthritis is a common rheumatologic disorder. It is estimated that 40 million Americans and 70% to 90% of persons older than 75 years are affected by osteoarthritis. Although symptoms of osteoarthritis occur earlier in women, the prevalence among men and women is equal. In addition to age, risk factors include joint injury, obesity, and mechanical stress. The diagnosis is largely clinical because radiographic findings do not always correlate with symptoms. Knowledge of the etiology and pathogenesis of the disease process aids in prevention and management. Acetaminophen and nonsteroidal anti-inflammatory medications remain first-line drugs. Agents such as cyclooxygenase-2 inhibitors and sodium hyaluronate joint injections offer new treatment alternatives. Complementary medication use has also increased. Therapeutic goals include minimizing symptoms and improving function.

Am Fam Physician 2002 Mar 1;65(5):841-8

A critical evaluation of side effect data on COX-2 inhibitors.

BACKGROUND: Celecoxib and rofecoxib have been used in Norway since 2000. These cyclooxygenase 2 inhibitors (COX-2 inhibitors) have no better clinical efficacy than older non-steroid anti-inflammatory drugs (NSAIDs) in the treatment of rheumatoid arthritis or osteoarthritis, but may possibly lead to a lower incidence of upper gastrointestinal ulcers. MATERIAL AND METHODS: Published and unpublished clinical data on side effects were examined and interpreted. The aim was to evaluate the general safety of these new drugs compared with older NSAIDs. RESULTS: The incidence of side effects is addressed in two large published studies comparing COX-2 inhibitors with other NSAIDs. Only rofecoxib showed an unequivocal lower incidence of complicated upper gastrointestinal ulcers. However, the incidence of serious side effects was significantly higher in the rofecoxib group. In the other study there was a trend towards more serious side effects in the celecoxib group. INTERPRETATION: The available clinical data do not suggest that COX-2 inhibitors are safer drugs than other NSAIDs.

Tidsskr Nor Laegeforen 2002 Feb 20;122(5):476-80

Prevalence of cardiovascular disease risk factors among US adults with self-reported osteoarthritis: data from the Third National Health and Nutrition Examination Survey.

OBJECTIVE: To estimate the prevalence of traditional risk factors for cardiovascular disease (CVD) among U.S. adults with osteoarthritis (OA). METHODS: Using survey data from the Third National Health and Nutrition Examination Survey, we estimated the prevalence of selected CVD risk factors among a U.S. OA and nonarthritic adult population. In additional analyses, we stratified the sample by gender and age (35-44, 45-64, and 65+ years) to further understand the CVD risk profile in an arthritic population and nonarthritic population. Relevant data on each survey participant's demographics, arthritis status, CVD risk factors, and sampling weights were obtained from the survey database. RESULTS: Of the 115.9 million US adults aged > or = 35 years, 24.3 million (21%) have OA. Hypertension is prevalent in approximately 40% of OA patients; 20% of the patients smoke and 11% have diabetes. Prevalence of high total cholesterol is estimated to be 32%, while prevalence of low high-density lipoprotein cholesterol is estimated at 13%. Approximately 37% of OA patients are estimated to have renal impairment, but less than 1% suffer from renal failure. CONCLUSION: National survey data suggest that, on average, U.S. adults with OA have a high prevalence of cardiovascular risk factors. These findings highlight the need to consider patients' comorbidites when selecting the appropriate treatment options.

Am J Manag Care 2002 Oct;8(15 Suppl):S383-91

Etiology, pathophysiology and conservative therapy of degenerative rheumatic diseases.

ETIOLOGY OF DEGENERATIVE JOINT DISEASES: Etiology of degenerative joint diseases is still not clearly understood and there is no specific management for this group of diseases. Various pathological conditions cause damage of the articular cartilage and lead to clinically and radiographically recognized impairment. Biomechanical, metabolic, genetic factors, inflammation and other risk factors contribute to development of osteoarthrosis. PATHOPHYSIOLOGY OF DEGENERATIVE JOINT DISEASES: Osteoarthrosis is characterized by progressive erosion of articular cartilage and bone overgrowth at the joint margins. Cartilage integrity requires balance between synthesis and degradation of matrix components. Chondrocytes react to various mechanical and chemical stresses in order to stabilize and restore the tissue. Failures in stabilizing and restoring the tissue lead to cartilage degeneration that may be irreversibile. For better understanding of conservative management of degenerative joint diseases it is important to know the impact of pathophysiology mechanisms on development of degenerative joint diseases. There is great variability in the rate of progression of erosive processes in articular cartilage in clinical, radiographic signs and course of the disease. This is in relation with many factors, as well as with management and response to therapy. TREATMENT OF DEGENERATIVE JOINT DISEASES: Treatment should vary depending on the severity of disease and patient's expectations and level of activity. Besides analgesic and anti-inflammatory drugs, conventional and not conventional treatment and techniques can be used for management of osteoarthrosis. Physical therapy and exercises are very important for maintaining muscle strength, joint stability and mobility, but should be closely monitored for optimal efficacy.

Med Pregl 2002 Jan-Feb;55(1-2):35-9

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