Premenopausal Stage Research Articles

Abnormalities of Bone Mineral Density and Bone Metabolism in Venezuelan Patients with Rheumatoid Arthritis

Patients with rheumatoid arthritis (RA) are at increased risk for osteoporosis and bone fractures. To our knowledge, the frequency of osteopenia and osteoporosis in patients with RA from Latin America has not been established. In this study, we have examined the bone mineral density (BMD) by dual-energy x-ray absorptiometry, as well as biochemical markers of bone metabolism, in a population of 85 Venezuelan RA patients. Twenty-seven patients (29.4%) fulfilled the World Health Organization's (WHO) criteria for either trabecular osteopenia or osteoporosis compared with 10 healthy controls (8.1%; odds ratio [OR] = 3.25; P = 0.004). In addition, 30 patients (26.4%) showed cortical osteopenia or osteoporosis compared with 5 healthy controls (4.0%; OR = 8.18; P < 0.00001). Past or concurrent use of prednisone or methotrexate was not related to decreased BMD. Rheumatoid patients showed increased serum levels of osteocalcin (P = 0.002) and 24-hour urine excretion of N-telopeptide cross-links (P = 0.03). The bone marker profiles suggest an increased bone turnover during the premenopausal stage in these patients. After menopause, a resorptive pattern seems to predominate, leading to accelerated bone mass loss in RA patients. In conclusion, Venezuelan female patients with RA may be at increased risk for osteopenia or osteoporosis, particularly after menopause. Our study supports the initiation of antiresorptive medication in Latin American premenopausal patients with RA, as in other ethnic groups, to diminish the risk of osteoporosis in the postmenopausal stage.

Bone resorption in post-menopausal women with normal and low BMD assessed with biochemical markers specific for telopeptide derived degradation products of collagen type I.

Biochemical markers of bone resorption can be used clinically to predict the risk of osteoporosis-related fractures (prognostic tool) and to assess the response of an osteoporotic patient to an antiresorptive therapy (monitoring tool). Our aim was to assess the ability of four currently marketed biochemical markers of bone resorption, based on the measurement of degradation products from collage type I telopeptides to monitor the elevated resorption associated with menopause. Women (846) were stratified for menopause, age, and bone mineral density and the following markers were measured: urinary cross-linked N-telopeptides of type I collagen (NTx), the levels of breakdown products of type I collagen C-telopeptides in serum (S-CTx), and in urine, by ELISA (U-CTx-E), and RIA (U-CTx-R). Furthermore, the ratio (alpha/beta) between the alphaL form of CTx measured in the CTx RIA and the betaL form measured in the ELISA was calculated. The mean difference was calculated for each marker in women with osteopenia (Op) or osteoporosis (PMO) (WHO definition) compared with healthy premenopausal (Pre) women and postmenopausal (N Post) women with normal bone mass. Serum CTx showed the highest elevation in post- compared with premenopausal women. All marker values were significantly higher in Op and PMO subjects compared with both Pre and to N Post women. Compared with premenopausal values, the largest elevation in both Op and PMO women was observed for serum CTx. Compared with N Post, urine NTx showed the highest increase in OP subjects. The alpha/beta CTx ratio was elevated in post- compared with Pre women, but there was no difference in the ratio among N Post, Op, or PMO women. In conclusion, postmenopausal women showed elevated turnover with all bone resorption markers, but with substantial individual variation in resorption levels. Furthermore, the turnover process in postmenopausal women appears to be quantitatively different from the premenopausal stage, apparent as altered alpha/beta CTx ratios.

Comparison of adjuvant therapy with tamoxifen and goserelin vs. CMF in premenopausal stage I and II hormone-responsive breast cancer patients: four-year results of Austrian Breast Cancer Study Group (ABCSG) trial 5

Comparison of adjuvant therapy with tamoxifen and goserelin vs. CMF in premenopausal stage I and II hormone-responsive breast cancer patients: four-year results of Austrian Breast Cancer Study Group (ABCSG) trial 5

Mechanistic findings of green tea as cancer preventive for humans.

Based on our initial work with green tea, in which repeated topical applications of (-)-epigallocatechin gallate (EGCG), the main green tea polyphenol, inhibited tumor promotion in a two-stage carcinogenesis experiment on mouse skin (Phytother Res 1, 44-47, 1987), numerous scientists have since provided so much additional evidence of the benefits of drinking green tea that it is now an acknowledged cancer preventive in Japan, and will possibly soon be recognized as such in other countries. Our work has so far produced several important results with EGCG and green tea: a wide range of target organs in animal experiments for cancer prevention, wide bioavailability of 3H-EGCG in various organs of mice, delayed cancer onset of patients with a history of consuming over 10 cups of green tea per day, and absence of any severe adverse effects among volunteers who took 15 green tea tablets per day (2.25 g green tea extracts, 337.5 mg EGCG, and 135 mg caffeine) for 6 months. This paper introduces three new findings: 1) EGCG interacted with the phospholipid bilayer membrane resulting in confirmation of the sealing effect of EGCG; 2) EGCG inhibited TNF-alpha gene expression in the cells and TNF-alpha release from the cells; 3) high consumption of green tea was closely associated with decreased numbers of axillary lymph node metastases among premenopausal Stage I and II breast cancer patients, and with increased expression of progesterone and estrogen receptors among postmenopausal ones. These results provide new insights into our understanding of the mechanisms of action of tea polyphenols and green tea extract as a cancer preventive.

Breast cancer incidence and screening practices among university faculty women.

T he incidence of breast cancer in the United States continues to rise, accounting for 32% of the cancer incidence among American women, according to 1994 cancer statistics.1 Breast cancer is the most commonly occurring cancer among women and is second only to lung cancer in causing cancer-related deaths, 18% versus 23%, respectively. In general, the earlier breast cancer is detected and treated, the greater the probability for a long disease-free survival. 2 Although increasing age, a family or self-history of breast or ovarian cancer, early age at menarche, late menopause, nulliparity, first full-term pregnancy after age 35, and Caucasian race are established risk factors for the disease, 3 there seems to be an increasing incidence among women with no known risk factors, at earlier ages, and during premenopausal and perimenopausal stages. The proportion of women age 65 years and older who are at increased risk due to their age alone will continue to rise, as the U.S. population of individuals 65 and older is expected to double from the 32 million in 1990 to 64 million in 2030. 4 Additional factors that have been found in some studies to be associated with increased risk, but are still controversial, include high fat diet, a dense tissue pattern on mammography, alcohol consumption, and estrogen and oral contraceptive use. 3 More recently, occupation has been proposed as a risk identifier by Rubin et al. 5 Rubin et al looked specifically at occupation as a risk identifier for breast cancer. 5 A database of occupationally coded death certificates was used to calculate age-adjusted, race-specific proportionate mortality ratios for breast cancer according to occupation. The findings of significant associations between occupation and frequency of breast cancer included high proportions of breast cancer death among white female professional, managerial, and clerical workers. Case-control analysis by occupation found the odds of breast cancer death to be between 2 and 2.23 times greater for teachers in higher education than for other occupational groups. The rising incidence figures may be due, in part, to women's increased awareness of early detection methods, such as breast self-examination, clinical breast examination, and screening mammography. 6 These factors in c o r n © 1995 by The Jacobs Institute of Women's Health 1049-3867/95/$9.5

Bioavailability Study of Menorest®, a New Estrogen Transdermal Delivery System, Compared with a Transdermal Reservoir System.

The aim of this study was to compare the bioavailability and plasma profiles of estradiol and estrone after repeated applications of 2 types of estradiol transdermal systems: a new adhesive matrix system (Menorest®) compared with a reference membrane/reservoir system (Estraderm®) and to evaluate their short term safety. This was an open, randomised, crossover study, with 2 treatment periods of 10.5 days separated by a 10-day washout period and with a 1-week follow-up. Participants were studied at Institut Aster, Paris, and Association de Recherche Thérapeutique (ART), Lyon, France, and included 31 healthy postmenopausal women, all volunteers aged between 49 and 67 years (mean 58 years). Each transdermal system was applied for three successive 3.5 day-wear periods (10.5 days) on the lower abdominal skin. Plasma estradiol and estrone concentrations were measured at steady-state, before and after the third application of each transdermal system at regular intervals over 106 hours. Cutaneous tolerance was assessed after each transdermal system removal. Although the extent of availability [area under the plasma concentration-time curve (AUC) and average plasma concentration (Cav)] was similar with both transdermal systems, their pharmacokinetic profiles were different, with Menorest® producing less fluctuating and more sustained plasma estradiol levels than the reference system. The mean estradiol to estrone Cav ratio was similar with the 2 transdermal systems and in the physiological range of premenopausal status. The incidence of adverse events was similar for both treatments, but a lower incidence of local erythema was observed with Menorest® (8.9%) than with the reference system (18.3%). In conclusion, during the entire wear period, Menorest® produced more sustained plasma estradiol levels with less fluctuations (40 to 72 ng/L) than the reservoir/ membrane system (18 to 102 ng/L). Menorest® gave estradiol plasma levels approximating the concentrations observed during the early to mid-follicular premenopausal stage, with a 2-fold lower incidence of erythema than with the reservoir/membrane system.

CMF versus oophorectomy in premenopausal (preMP) stage II breast cancer (BC)

CMF versus oophorectomy in premenopausal (preMP) stage II breast cancer (BC)

Sequelae of lateral ovarian transposition in irradiated cervical cancer patients

Lateral ovarian transposition (LOT) is a useful technique for preserving ovarian function in “high-risk” premenopausal Stage I cervix cancer patients who undergo hysterectomy and subsequent postoperative whole pelvic radiation therapy. From 1978 to 1988, 38 FIGO Stage I cervical cancer patients underwent LOT as part of their initial operative procedure and 14 of these patients (37%) subsequently received pelvic radiation therapy (LOT + RT) because of pathological findings such as metastatic pelvic lymph node involvement or positive surgical margins(13 patients) or recurrent disease (1 patient). Ten (71%) of the 14 (LOT + RT) patients have maintained ovarian function with a median follow-up of 35 months. Preservation of ovarian function was directly related to the estimated scatter dose to the ovaries. For patients whose estimated ovarian dose was 300 cGy or less, only 1 of 9 patients (11%) underwent menopause, whereas 3 of 5 patients (60%) became menopausal if the ovarian dose was more than 300 cGy. The placement of the ovaries was also crucial for preservation of ovarian function, with 100% of the patients developing menopause if the ovaries were placed below the iliac crest. A major side effect of LOT was the development of symptomatic ovarian cysts in 7 (18%) of the 38 Stage I patients who underwent LOT. In the 24 patients who underwent LOT alone without RT, the incidence of symptomatic ovarian cysts was 25% compared to only 7% of the patients who underwent LOT + RT, although this difference was not statistically significant ( p = .18).

Hormone replacement before menopause. Is it a good idea?

The efficacy and safety of hormone replacement therapy for postmenopausal women are no longer issues of heated debate. The same cannot be said of hormone replacement therapy for women approaching menopause who, though still menstruating, have the emotional and physical symptoms of clinical menopause. In this article, Dr Wells presents a solid case advocating such treatment during the premenopausal stage of the climacteric.

Endocrine effects of adjuvant chemotherapy in premenopausal women: suggestions for the future.

Controversy continues to exist concerning the reason for an apparently greater therapeutic effect of postoperative chemotherapy in premenopausal Stage 2 patients as compared with postmenopausal patients (Brincker et al. 1987). The two major reasons suggested for the apparent difference have been a lower dose delivery in postmenopausal patients (Bonadonna and Valagussa 1981) and a drug-induced ovarian ablation in premenopausal patients (Pouquier 1978). The dosing hypothesis is not fully supported by other trials such as that of the Eastern Cooperative Oncology Group (ECOG), wherein the results for postmenopausal patients were similar to those of the initial Milan experience (Tormey et al. 1986). Similary, the differences observed in premenopausal patients with postoperative oophorectomy did not always provide a significant effect or appear to be as great as has been observed with postoperative chemotherapy (Cole 1975; Fisher 1971; Meakin 1986). This chapter examines this controversy further and develops a hypothesis to explain the apparently greater therapeutic impact of chemotherapy among Stage 2 premenopausal patients. The hypothesis suggests a treatment approach which could be tested in future premenopausal adjuvant trials.

Hormonal status of breast cancer. III. Further analysis of ovarian-adrenal dysfunction.

Detailed studies of urinary steroids in patients with breast cancer and normal controls have shown that abnormal aging processes and depressed corpus luteum function were associated with the presence of this form of cancer. The ratio of androsterone to tetrahydrocortisol, an index of the aging process, was significantly lower in a breast cancer group than in a normal group at both premenopausal and postmenopausal stages. In premenopausal women, the ratio decreased in the order of rural controls, urban controls, and patients with breast cancer. It was indicated that the ratio may serve as a measure of risk for breast cancer. Aside from the general depression of menstruation-dependent steroids, breast cancer was associated with disproportionately low excretions of prenanediol and pregnanetriol within the menstruation-dependent steroid family. The notion that this finding reflects the delay or complete failure of ovulation was supported by a reduced parturition rate of our patients with breast cancer as compared with that of our normal controls. The physiologic significance of steroidal disturbances was considered in relation to the genesis of breast cancer.

Changes of hypophysio-ovarian endocrinological function by aging in woman.

Serum estradiol, progesterone, LH and FSH were concomitantly measured by radioimmunoassay in pre- and post-menopausal women in an attempt to study hormonal changes occurring in menopause. The level of serum estradiol in post-menopausal women was maintained at the same level as in pre-menopausal stage within one year after menopause and thereafter began to decrease to the senile minimal level. On the other hand, the mean serum levels of FSH and LH were elevated gradually after menopause. At the conclusion of this study, it was suggested that the key point of the mechanism of menopause may exist not only in the depletion of ovarian function but in the change of the regulatory mechanism of LH and FSH secretion by aging.