Most combination oral contraceptives contain ethinyl estradiol and a progestin. A new and novel o... more Most combination oral contraceptives contain ethinyl estradiol and a progestin. A new and novel oral contraceptive formulation combines estradiol valerate (E2V) with dienogest (DNG) in a four-phase dosing regimen. 17β-estradiol is a naturally-occurring estrogen, and a contraceptive pill containing such an estrogen offers potential benefits with regard to metabolic side effects and adverse events. Dienogest is derived from 19-nortestosterone and exerts profound progestational effects on the endometrium, but it differs from other progestins in its class by its antiandrogenic activity. Estradiol valerate plus dienogest (E2V/DNG) is now available in a four-phasic regimen that integrates an estrogen stepdown and progestin stepup dosing approach along with a short two-day hormone-free interval. This regimen offers safe, reliable contraception and has been shown to be an effective treatment for heavy menstrual bleeding. Metabolic effects and adverse events appear similar to those reported with oral contraceptives containing ethinyl estradiol.
American Journal of Obstetrics and Gynecology, 2001
Oral contraceptives are one of the most highly effective forms of contraception and provide many ... more Oral contraceptives are one of the most highly effective forms of contraception and provide many short- and long-term noncontraceptive health benefits. They control menstrual cycle irregularities, such as breakthrough bleeding and amenorrhea, and are effective in treating dysfunctional uterine bleeding. In addition, for decades after oral contraceptive use is discontinued they are associated with substantial decreases in the risk of ovarian cancer (up to 80%) and of endometrial cancer (40%-50%), and nearly eliminate benign functional ovarian cysts. Long-term oral contraceptive use confers protection against benign breast disease and colorectal cancer, may help prevent rheumatoid arthritis, decreases ectopic pregnancy and hospitalizations for pelvic inflammatory disease, and helps preserve bone mineral density to reduce risk of fractures. Large bodies of evidence from extensive research have clarified the perceived association of oral contraceptive use with cardiovascular disease and with breast cancer. Findings indicate that there is no increased risk of myocardial infarction or stroke associated with oral contraceptive use in healthy, nonsmoking, normotensive women. Although there is a 3- to 4-fold increased risk of venous thromboembolism with current oral contraceptive use, the absolute risk is very small and is half that associated with pregnancy. Women of all reproductive ages, including perimenopausal women, can realize many health benefits through oral contraceptive use, including improved health status later in life.
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service... more This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Contributors PMM contributed to study conception and design, study administration, technical support, acquisition of data, data analysis, interpretation of data, drafting of the manuscript, and final review of the manuscript. LHR contributed to study conception and design, data analysis (as lead statistician), interpretation of data, drafting of the manuscript, and final review of the manuscript. AS contributed to study administration, technical support, acquisition of data, interpretation of data and final review of the manuscript. LD contributed to study administration, technical support, acquisition of data, interpretation of data and final review of the manuscript. LPS contributed to study conception and design and final review of the manuscript. SB contributed to study conception and design, study administration, technical support, and final review of the manuscript. DRW contributed to study conception and design, study administration, data analysis, interpretation of data, drafting of the manuscript, and final review of the manuscript.
Purpose: Despite strong association between genetic ancestry and carrier status, current carrier-... more Purpose: Despite strong association between genetic ancestry and carrier status, current carrier-screening guidelines recommend testing for a limited set of conditions based on patient self-reported ethnicity, which conflates genetic and cultural factors. Materials and Methods: For 93,419 individuals undergoing a 96-gene expanded carrier screen (ECS), correspondence was assessed among carrier status, self-reported ethnicity, and a dual-component genetic ancestry (e.g., 75% African/25% European) calculated from sequencing data. Results: Self-reported ethnicity was an imperfect indicator of genetic ancestry, with 9% of individuals having >50% genetic ancestry from a lineage inconsistent with self-reported ethnicity. Self-reported ethnicity-based carrier-screening guidelines are incomplete, as several conditions not included in guidelines had similarly strong correlation between carrier rate and genetic ancestry as conditions included in screening guidelines. Limitations of self-rep...
Background. To evaluate the efficacy of a succinate-based dietary supplement (SBDS; Amberen) in s... more Background. To evaluate the efficacy of a succinate-based dietary supplement (SBDS; Amberen) in symptomatic menopausal women using a larger sample size derived by pooling data from two identical trials. Methods. Raw data were pooled from two identical randomized, multicenter, double-blinded, placebo-controlled, 90-day clinical trials. Women aged 42–60 years with mild to moderate vasomotor and psychosomatic menopausal symptoms were included (114 in the treatment group and 113 in the placebo group). Symptoms were assessed by the Greene Climacteric Scale and State-Trait Anxiety Inventory. Changes in body mass index, body weight, waist and hip circumferences, and plasma levels of follicle stimulating hormone, luteinizing hormone, estradiol, leptin, and apolipoproteins A1 and B were also evaluated. Results. SBDS use resulted in significant improvements in several endpoints including alleviation of 16 of 21 menopausal symptoms (p≤0.05, Greene Scale) and a decrease in anxiety (p<0.0001,...
Introduction: Adnexal or pelvic mass is a finding that commonly raises suspicion for malignancy, ... more Introduction: Adnexal or pelvic mass is a finding that commonly raises suspicion for malignancy, especially for ovarian cancer. Proper identification prior to surgery would permit appropriate referral to a specialty center in cases likely to be ovarian cancer, as optimal outcomes in such cases are obtained when surgical staging and treatment are provided at the time of initial surgery. Methods: We compared the screening capabilities of two in vitro diagnostic multivariate index assays (IVDMIAs), a new IVDMIA (second-generation multivariate index assay: MIA2G) and a currently used triage algorithm (Risk of Ovarian Malignancy Assay: ROMA).
Late second trimester dilation and evacuation is a challenging subset of surgical abortion. Among... more Late second trimester dilation and evacuation is a challenging subset of surgical abortion. Among the reasons for this is the degree of cervical dilation required to safely extricate fetal parts. Cervical dilation is traditionally achieved by placing multiple sets of osmotic dilators over two or more days prior to the evacuation procedure; however, there is interest in shortening cervical preparation time. The use of adjuvant mifepristone and misoprostol in conjunction with osmotic dilators has been studied for this purpose, and their use demonstrates that adequate cervical dilation can be achieved in less time than with dilators alone. We present a review of the current evidence surrounding adjunctive agents for cervical preparation, and contend that for women presenting for surgical abortion care above 19 weeks gestation, the use of adjunctive mifepristone and/or misoprostol should be strongly considered along with osmotic dilator insertion when cervical preparation in less than 24 h is needed.
Journal of assisted reproduction and genetics, 2018
Patients undergoing in-vitro fertilization (IVF) with preimplantation genetic screening (PGS) are... more Patients undergoing in-vitro fertilization (IVF) with preimplantation genetic screening (PGS) are counseled about the limitations of this technique. As part of the consent process for PGS, physicians recommend diagnostic genetic testing performed in early pregnancy to definitively rule out chromosomal abnormalities. We have noted anecdotally, however, that few patients undergo the recommended diagnostic testing. In this study, we are examining if women who conceived using IVF-PGS did early pregnancy chromosomal testing, and if they did, what type of testing they had. This study was performed from 2015 to 2017 in the Division of Reproductive Endocrinology and Infertility at Northwestern University. We included patients who became pregnant after IVF-PGS who were seen by the Division of Reproductive Genetics and non-PGS control group. Sixty-eight patients were included. A total of 50 patients (73.5%) opted for non-invasive prenatal screening; 5 (7.4%) had invasive testing (4 had chorio...
The use of effective and reversible contraception is characterized by many non-contraceptive bene... more The use of effective and reversible contraception is characterized by many non-contraceptive benefits distinct from its ability to prevent pregnancy. Notably, the use of hormonal and non-hormonal birth control methods is known to impact the risk for developing certain female genital cancers as well as breast and colon cancers. We present here the current understanding of the role of effective and reversible contraceptives in the prevention and development of female genital cancers along with breast and colon cancers. Despite ongoing but unsubstantiated concerns regarding the use of hormonal and intrauterine contraceptives for a variety of clinical outcomes including cancer, contraceptive use in high- and low-risk reproductive-aged women remains an important part of cancer risk reduction for many malignancies.
Journal of adolescent and young adult oncology, Jan 11, 2016
Mutations in the BRCA1/2 genes are associated with breast and ovarian cancer susceptibility. Rece... more Mutations in the BRCA1/2 genes are associated with breast and ovarian cancer susceptibility. Recent studies have suggested that the BRCA mutation might be associated with occult primary ovarian insufficiency. To evaluate fertility, several studies have validated anti-Mullerian hormone (AMH) as a direct biomarker for ovarian aging and it is considered a quantitative marker of ovarian reserve. We hypothesize that BRCA1 gene mutations will be negatively associated with AMH levels. We evaluated 124 women aged 18-45 years participating in the Northwestern Ovarian Cancer Early Detection and Prevention Program. Patients with a history of cancer, ovarian surgery, or exposure to chemotherapy were excluded. Linear and logistic regression modeling were performed to evaluate the association between AMH levels, age, and BRCA1 mutation. In logistic models, the outcome 'low AMH' was defined as AMH <0.05 ng/mL. Logistic regression models were used to adjust for other factors, including b...
Despite the wide variety of reversible contraceptives, unintended pregnancy rates in developed na... more Despite the wide variety of reversible contraceptives, unintended pregnancy rates in developed nations are still considered markedly elevated by most epidemiologists and clinicians. Indeed, the US has one of the highest unintended pregnancy rates among the industrialized nations of the world. Although many factors appear to influence this problem, what may play an important role in this apparent paradox is the process by which a woman obtains contraception. Although most nonbarrier methods have similar efficacy, the ability to use that method consistently and correctly will determine whether it provides maximal contraception. Oral contraceptives are the most popular method in the US; accordingly, the process by which US women obtain their contraception may not take into account the desire of many women to use nondaily methods. The recent introduction of nondaily methods in the US and elsewhere has provided more choice so that a successful contraceptive decision can be made in the first instance rather than after an adverse clinical outcome or unintended pregnancy with a method not as well suited to that woman&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s lifestyle. These new methods are not characterized by improved safety or efficacy; rather, they have novel components or delivery systems that may provide important options to women who may not be able to or willing to use existing methods of contraception. The transdermal patch, vaginal ring, and monthly injectable are combination estrogen/progestogen methods characterized by novel delivery systems and compliance regimens. The single rod implant is a facile and well accepted method that has not yet been approved for use in the US but has been an increasingly popular choice elsewhere. The levonorgestrel intrauterine system has been used in Europe for over 10 years and has recently been introduced in the US. This intrauterine contraceptive provides high efficacy and reliability, and may have considerable noncontraceptive benefit with regard to the nonsurgical treatment of uterine bleeding problems and endometrial protection for menopausal hormone therapy. The increasing popularity of these methods can be considered a testament to the desire of women to consider nondaily contraceptives as first-line, mainstream options. It is hoped that increasing use of these methods will lead to a considerable decrease in the rate of unintended pregnancy.
Analysis of sister chromatid exchange (SCE) in chorionic villus cells may become useful in measur... more Analysis of sister chromatid exchange (SCE) in chorionic villus cells may become useful in measuring the response of fetal tissues to clastogens or mutagens or for prenatal diagnosis of chromosome breakage syndromes such as Bloom syndrome. Previous studies have failed to analyze cytotrophoblastic cells and mesenchymal core cells, or have found no difference between SCE frequencies in directly prepared and cultured cells. Our data indicate significant differences in SCE frequencies between the two cell types: SCE frequency in directly prepared cytotrophoblasts was 6.73 SCE/cell +/- 1.6, whereas SCE frequency in cultured mesenchymal core cells was 10.31 SCE/cell +/- 0.49 (P less than 0.001). SCE analyses involving chorionic villi must take into account cell type.
Monitoring the efficacy associated with antiresorptive therapy is an intuitive yet integral part ... more Monitoring the efficacy associated with antiresorptive therapy is an intuitive yet integral part of successful osteoporosis management. Although response rates to bisphosphonates in clinical trials-as judged by changes in bone mineral density (BMD)-are generally high, a small percentage of compliant patients do not respond. Accordingly, monitoring may help identify noncompliant patients and allow for other, possibly more successful, therapeutic interventions. Dual energy x-ray absorptiometry is the accepted method of assessing BMD to determine the need for treatment and to monitor its effects. Change in BMD is considered a valid intermediate end point for efficacy of fracture risk reduction. However, clinical trials have shown that the reduction in fracture risk associated with antiresorptive therapy may occur before changes in BMD become apparent. Vertebral fracture benefit is observed even among women who maintain rather than gain BMD during antiresorptive therapy. Clinical trials show that suppression of bone turnover markers after as little as 3 months of therapy is strongly associated with reductions in risk for fracture. Although formal guidelines for monitoring bone turnover markers do not yet exist, there are data to suggest that changes in these markers are valid intermediate endpoints for efficacy of fracture risk reduction that may provide valuable additional data on therapeutic success, particularly early in treatment and before changes in BMD become apparent.
Dietary supplements containing black cohosh are alternatives to conventional hormone replacement ... more Dietary supplements containing black cohosh are alternatives to conventional hormone replacement therapy in menopause. This study investigates the maximum tolerated dose of a 75% ethanol extract of black cohosh and determines the pharmacokinetics of one of its most abundant triterpene glycosides, 23-epi-26-deoxyactein. single doses of black cohosh extract containing 1.4, 2.8, or 5.6 mg of 23-epi-26-deoxyactein were administered to 15 healthy, menopausal women. serial blood samples and 24-h urine samples were obtained; blood chemistry, hormonal levels, and 23-epi-26-deoxyactein levels were determined. no acute toxicity or estrogenic hormone effects were observed. pharmacokinetic analyses of 23-epi-26-deoxyactein in sera indicated that the maximum concentration and area under the curve increased proportionately with dosage, and that the half-life was ~2 h for all dosages. less than 0.01% of the 23-epi-26-deoxyactein was recovered in urine 24 h after administration. no phase i or phase ii metabolites were observed either in clinical specimens or in vitro.
Most combination oral contraceptives contain ethinyl estradiol and a progestin. A new and novel o... more Most combination oral contraceptives contain ethinyl estradiol and a progestin. A new and novel oral contraceptive formulation combines estradiol valerate (E2V) with dienogest (DNG) in a four-phase dosing regimen. 17β-estradiol is a naturally-occurring estrogen, and a contraceptive pill containing such an estrogen offers potential benefits with regard to metabolic side effects and adverse events. Dienogest is derived from 19-nortestosterone and exerts profound progestational effects on the endometrium, but it differs from other progestins in its class by its antiandrogenic activity. Estradiol valerate plus dienogest (E2V/DNG) is now available in a four-phasic regimen that integrates an estrogen stepdown and progestin stepup dosing approach along with a short two-day hormone-free interval. This regimen offers safe, reliable contraception and has been shown to be an effective treatment for heavy menstrual bleeding. Metabolic effects and adverse events appear similar to those reported with oral contraceptives containing ethinyl estradiol.
American Journal of Obstetrics and Gynecology, 2001
Oral contraceptives are one of the most highly effective forms of contraception and provide many ... more Oral contraceptives are one of the most highly effective forms of contraception and provide many short- and long-term noncontraceptive health benefits. They control menstrual cycle irregularities, such as breakthrough bleeding and amenorrhea, and are effective in treating dysfunctional uterine bleeding. In addition, for decades after oral contraceptive use is discontinued they are associated with substantial decreases in the risk of ovarian cancer (up to 80%) and of endometrial cancer (40%-50%), and nearly eliminate benign functional ovarian cysts. Long-term oral contraceptive use confers protection against benign breast disease and colorectal cancer, may help prevent rheumatoid arthritis, decreases ectopic pregnancy and hospitalizations for pelvic inflammatory disease, and helps preserve bone mineral density to reduce risk of fractures. Large bodies of evidence from extensive research have clarified the perceived association of oral contraceptive use with cardiovascular disease and with breast cancer. Findings indicate that there is no increased risk of myocardial infarction or stroke associated with oral contraceptive use in healthy, nonsmoking, normotensive women. Although there is a 3- to 4-fold increased risk of venous thromboembolism with current oral contraceptive use, the absolute risk is very small and is half that associated with pregnancy. Women of all reproductive ages, including perimenopausal women, can realize many health benefits through oral contraceptive use, including improved health status later in life.
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service... more This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Contributors PMM contributed to study conception and design, study administration, technical support, acquisition of data, data analysis, interpretation of data, drafting of the manuscript, and final review of the manuscript. LHR contributed to study conception and design, data analysis (as lead statistician), interpretation of data, drafting of the manuscript, and final review of the manuscript. AS contributed to study administration, technical support, acquisition of data, interpretation of data and final review of the manuscript. LD contributed to study administration, technical support, acquisition of data, interpretation of data and final review of the manuscript. LPS contributed to study conception and design and final review of the manuscript. SB contributed to study conception and design, study administration, technical support, and final review of the manuscript. DRW contributed to study conception and design, study administration, data analysis, interpretation of data, drafting of the manuscript, and final review of the manuscript.
Purpose: Despite strong association between genetic ancestry and carrier status, current carrier-... more Purpose: Despite strong association between genetic ancestry and carrier status, current carrier-screening guidelines recommend testing for a limited set of conditions based on patient self-reported ethnicity, which conflates genetic and cultural factors. Materials and Methods: For 93,419 individuals undergoing a 96-gene expanded carrier screen (ECS), correspondence was assessed among carrier status, self-reported ethnicity, and a dual-component genetic ancestry (e.g., 75% African/25% European) calculated from sequencing data. Results: Self-reported ethnicity was an imperfect indicator of genetic ancestry, with 9% of individuals having >50% genetic ancestry from a lineage inconsistent with self-reported ethnicity. Self-reported ethnicity-based carrier-screening guidelines are incomplete, as several conditions not included in guidelines had similarly strong correlation between carrier rate and genetic ancestry as conditions included in screening guidelines. Limitations of self-rep...
Background. To evaluate the efficacy of a succinate-based dietary supplement (SBDS; Amberen) in s... more Background. To evaluate the efficacy of a succinate-based dietary supplement (SBDS; Amberen) in symptomatic menopausal women using a larger sample size derived by pooling data from two identical trials. Methods. Raw data were pooled from two identical randomized, multicenter, double-blinded, placebo-controlled, 90-day clinical trials. Women aged 42–60 years with mild to moderate vasomotor and psychosomatic menopausal symptoms were included (114 in the treatment group and 113 in the placebo group). Symptoms were assessed by the Greene Climacteric Scale and State-Trait Anxiety Inventory. Changes in body mass index, body weight, waist and hip circumferences, and plasma levels of follicle stimulating hormone, luteinizing hormone, estradiol, leptin, and apolipoproteins A1 and B were also evaluated. Results. SBDS use resulted in significant improvements in several endpoints including alleviation of 16 of 21 menopausal symptoms (p≤0.05, Greene Scale) and a decrease in anxiety (p<0.0001,...
Introduction: Adnexal or pelvic mass is a finding that commonly raises suspicion for malignancy, ... more Introduction: Adnexal or pelvic mass is a finding that commonly raises suspicion for malignancy, especially for ovarian cancer. Proper identification prior to surgery would permit appropriate referral to a specialty center in cases likely to be ovarian cancer, as optimal outcomes in such cases are obtained when surgical staging and treatment are provided at the time of initial surgery. Methods: We compared the screening capabilities of two in vitro diagnostic multivariate index assays (IVDMIAs), a new IVDMIA (second-generation multivariate index assay: MIA2G) and a currently used triage algorithm (Risk of Ovarian Malignancy Assay: ROMA).
Late second trimester dilation and evacuation is a challenging subset of surgical abortion. Among... more Late second trimester dilation and evacuation is a challenging subset of surgical abortion. Among the reasons for this is the degree of cervical dilation required to safely extricate fetal parts. Cervical dilation is traditionally achieved by placing multiple sets of osmotic dilators over two or more days prior to the evacuation procedure; however, there is interest in shortening cervical preparation time. The use of adjuvant mifepristone and misoprostol in conjunction with osmotic dilators has been studied for this purpose, and their use demonstrates that adequate cervical dilation can be achieved in less time than with dilators alone. We present a review of the current evidence surrounding adjunctive agents for cervical preparation, and contend that for women presenting for surgical abortion care above 19 weeks gestation, the use of adjunctive mifepristone and/or misoprostol should be strongly considered along with osmotic dilator insertion when cervical preparation in less than 24 h is needed.
Journal of assisted reproduction and genetics, 2018
Patients undergoing in-vitro fertilization (IVF) with preimplantation genetic screening (PGS) are... more Patients undergoing in-vitro fertilization (IVF) with preimplantation genetic screening (PGS) are counseled about the limitations of this technique. As part of the consent process for PGS, physicians recommend diagnostic genetic testing performed in early pregnancy to definitively rule out chromosomal abnormalities. We have noted anecdotally, however, that few patients undergo the recommended diagnostic testing. In this study, we are examining if women who conceived using IVF-PGS did early pregnancy chromosomal testing, and if they did, what type of testing they had. This study was performed from 2015 to 2017 in the Division of Reproductive Endocrinology and Infertility at Northwestern University. We included patients who became pregnant after IVF-PGS who were seen by the Division of Reproductive Genetics and non-PGS control group. Sixty-eight patients were included. A total of 50 patients (73.5%) opted for non-invasive prenatal screening; 5 (7.4%) had invasive testing (4 had chorio...
The use of effective and reversible contraception is characterized by many non-contraceptive bene... more The use of effective and reversible contraception is characterized by many non-contraceptive benefits distinct from its ability to prevent pregnancy. Notably, the use of hormonal and non-hormonal birth control methods is known to impact the risk for developing certain female genital cancers as well as breast and colon cancers. We present here the current understanding of the role of effective and reversible contraceptives in the prevention and development of female genital cancers along with breast and colon cancers. Despite ongoing but unsubstantiated concerns regarding the use of hormonal and intrauterine contraceptives for a variety of clinical outcomes including cancer, contraceptive use in high- and low-risk reproductive-aged women remains an important part of cancer risk reduction for many malignancies.
Journal of adolescent and young adult oncology, Jan 11, 2016
Mutations in the BRCA1/2 genes are associated with breast and ovarian cancer susceptibility. Rece... more Mutations in the BRCA1/2 genes are associated with breast and ovarian cancer susceptibility. Recent studies have suggested that the BRCA mutation might be associated with occult primary ovarian insufficiency. To evaluate fertility, several studies have validated anti-Mullerian hormone (AMH) as a direct biomarker for ovarian aging and it is considered a quantitative marker of ovarian reserve. We hypothesize that BRCA1 gene mutations will be negatively associated with AMH levels. We evaluated 124 women aged 18-45 years participating in the Northwestern Ovarian Cancer Early Detection and Prevention Program. Patients with a history of cancer, ovarian surgery, or exposure to chemotherapy were excluded. Linear and logistic regression modeling were performed to evaluate the association between AMH levels, age, and BRCA1 mutation. In logistic models, the outcome 'low AMH' was defined as AMH <0.05 ng/mL. Logistic regression models were used to adjust for other factors, including b...
Despite the wide variety of reversible contraceptives, unintended pregnancy rates in developed na... more Despite the wide variety of reversible contraceptives, unintended pregnancy rates in developed nations are still considered markedly elevated by most epidemiologists and clinicians. Indeed, the US has one of the highest unintended pregnancy rates among the industrialized nations of the world. Although many factors appear to influence this problem, what may play an important role in this apparent paradox is the process by which a woman obtains contraception. Although most nonbarrier methods have similar efficacy, the ability to use that method consistently and correctly will determine whether it provides maximal contraception. Oral contraceptives are the most popular method in the US; accordingly, the process by which US women obtain their contraception may not take into account the desire of many women to use nondaily methods. The recent introduction of nondaily methods in the US and elsewhere has provided more choice so that a successful contraceptive decision can be made in the first instance rather than after an adverse clinical outcome or unintended pregnancy with a method not as well suited to that woman&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s lifestyle. These new methods are not characterized by improved safety or efficacy; rather, they have novel components or delivery systems that may provide important options to women who may not be able to or willing to use existing methods of contraception. The transdermal patch, vaginal ring, and monthly injectable are combination estrogen/progestogen methods characterized by novel delivery systems and compliance regimens. The single rod implant is a facile and well accepted method that has not yet been approved for use in the US but has been an increasingly popular choice elsewhere. The levonorgestrel intrauterine system has been used in Europe for over 10 years and has recently been introduced in the US. This intrauterine contraceptive provides high efficacy and reliability, and may have considerable noncontraceptive benefit with regard to the nonsurgical treatment of uterine bleeding problems and endometrial protection for menopausal hormone therapy. The increasing popularity of these methods can be considered a testament to the desire of women to consider nondaily contraceptives as first-line, mainstream options. It is hoped that increasing use of these methods will lead to a considerable decrease in the rate of unintended pregnancy.
Analysis of sister chromatid exchange (SCE) in chorionic villus cells may become useful in measur... more Analysis of sister chromatid exchange (SCE) in chorionic villus cells may become useful in measuring the response of fetal tissues to clastogens or mutagens or for prenatal diagnosis of chromosome breakage syndromes such as Bloom syndrome. Previous studies have failed to analyze cytotrophoblastic cells and mesenchymal core cells, or have found no difference between SCE frequencies in directly prepared and cultured cells. Our data indicate significant differences in SCE frequencies between the two cell types: SCE frequency in directly prepared cytotrophoblasts was 6.73 SCE/cell +/- 1.6, whereas SCE frequency in cultured mesenchymal core cells was 10.31 SCE/cell +/- 0.49 (P less than 0.001). SCE analyses involving chorionic villi must take into account cell type.
Monitoring the efficacy associated with antiresorptive therapy is an intuitive yet integral part ... more Monitoring the efficacy associated with antiresorptive therapy is an intuitive yet integral part of successful osteoporosis management. Although response rates to bisphosphonates in clinical trials-as judged by changes in bone mineral density (BMD)-are generally high, a small percentage of compliant patients do not respond. Accordingly, monitoring may help identify noncompliant patients and allow for other, possibly more successful, therapeutic interventions. Dual energy x-ray absorptiometry is the accepted method of assessing BMD to determine the need for treatment and to monitor its effects. Change in BMD is considered a valid intermediate end point for efficacy of fracture risk reduction. However, clinical trials have shown that the reduction in fracture risk associated with antiresorptive therapy may occur before changes in BMD become apparent. Vertebral fracture benefit is observed even among women who maintain rather than gain BMD during antiresorptive therapy. Clinical trials show that suppression of bone turnover markers after as little as 3 months of therapy is strongly associated with reductions in risk for fracture. Although formal guidelines for monitoring bone turnover markers do not yet exist, there are data to suggest that changes in these markers are valid intermediate endpoints for efficacy of fracture risk reduction that may provide valuable additional data on therapeutic success, particularly early in treatment and before changes in BMD become apparent.
Dietary supplements containing black cohosh are alternatives to conventional hormone replacement ... more Dietary supplements containing black cohosh are alternatives to conventional hormone replacement therapy in menopause. This study investigates the maximum tolerated dose of a 75% ethanol extract of black cohosh and determines the pharmacokinetics of one of its most abundant triterpene glycosides, 23-epi-26-deoxyactein. single doses of black cohosh extract containing 1.4, 2.8, or 5.6 mg of 23-epi-26-deoxyactein were administered to 15 healthy, menopausal women. serial blood samples and 24-h urine samples were obtained; blood chemistry, hormonal levels, and 23-epi-26-deoxyactein levels were determined. no acute toxicity or estrogenic hormone effects were observed. pharmacokinetic analyses of 23-epi-26-deoxyactein in sera indicated that the maximum concentration and area under the curve increased proportionately with dosage, and that the half-life was ~2 h for all dosages. less than 0.01% of the 23-epi-26-deoxyactein was recovered in urine 24 h after administration. no phase i or phase ii metabolites were observed either in clinical specimens or in vitro.
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