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Biomedical subjects

James A Simon

Publications and source records attributed to James A Simon.

At least 19 recordsLinked to original sources
PubMed2006

Economic burden of endometriosis.

OBJECTIVE: To comprehensively review and evaluate the direct costs of endometriosis. DESIGN AND SETTING: We systematically reviewed studies published since 1990, and conducted an analysis of publicly available national databases (Healthcare Cost and Utilization Project and National Ambulatory Medical Care Survey/National Hospital Ambulatory Medical Care Survey) in the United States. We assessed: [1] the overall economic impact of endometriosis; [2] the direct costs associated with specific treatments; and [3] the indirect costs of endometriosis associated with reduced work productivity. RESULTS: Of 13 published studies meeting inclusion criteria, 11 (85%) addressed direct costs, a few studies addressed outpatient costs or indirect costs, and no study quantified the economic impact among adolescents. Direct endometriosis-related costs were considerable and appeared driven by hospitalizations. Our database analysis found: [1] as endometriosis-related hospital length of stay steadily declined from 1993 to 2002, per-patient cost increased 61%; [2] adolescents (aged 10-17 years) had endometriosis-related hospitalizations; [3] approximately 50% of >600,000 endometriosis-related ambulatory patient visits involved specialist care; and [4] females 23 years old or younger constituted >20% of endometriosis-related outpatient visits. CONCLUSIONS: Health economic information for endometriosis is scarce, limiting our understanding of its overall economic impact. Nevertheless, the literature and other available data suggest that endometriosis places a considerable burden on patients and society.

Adolescent↗
PubMed2006

The length of perimenopausal menstrual cycles increases later and to a greater degree than previously reported.

OBJECTIVE: To demonstrate that the perimenopausal increase in menstrual cycle length presented by Treloar et al. was biased by misidentified menopause dates, mean values classified by calendar year, and exclusion of menstrual cycles straddling two calendar years; and to use the revised data to investigate women's experiences of longer perimenopausal cycles. DESIGN: Secondary analysis of prospectively collected menstrual cycle data. SETTING: Center for Population and Health, Georgetown University. PATIENT(S): One hundred twenty white, college-educated, US women in the Tremin Research Program on Women's Health. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Mean cycle length and time spent in >40-day cycles, by year before menopause. RESULT(S): Mean estimates for each of the 4 years before menopause were 30.48, 35.02, 45.15, and 80.22 days, respectively, compared with the original analysis: 33.60, 43.91, 55.87, and 54.58 days. In the year before menopause, the majority of women spent >or=75% of their time in cycles >40 days long. CONCLUSION(S): Treloar's estimates of mean cycle length were biased. Long cycles occurred throughout perimenopause, but the largest increase in mean cycle length did not occur until the final year before menopause. New estimates of the time spent in cycles >40 days may be useful clinically as well as epidemiologically for assessing menopausal onset and symptomatology.

Adult↗
PubMed2006

Effects of low-dose norethindrone acetate plus ethinyl estradiol (0.5 mg/2.5 microg) in women with postmenopausal symptoms: updated analysis of three randomized, controlled trials.

BACKGROUND: Based on the potential risks of post-menopausal hormone therapy (HT) found by the Women's Health Initiative, guidelines for HT now recommend use of the lowest effective dose and shortest treatment duration consistent with individual treatment goals. Current (2003) guidance established by the US Food and Drug Administration (FDA) recommends that clinical assessments of HT include women with more frequent and more intense vasomotor symptoms than previously studied. Therefore, this analysis was conducted to further assess the efficacy of a low-dose combination of norethindrone acetate and ethinyl estradiol (NA/EE) previously assessed in dose-ranging studies, while meeting conservative FDA trial design and analysis criteria. OBJECTIVES: The aim of this post hoc analysis and overview was to present data on the efficacy and tolerability of a low-dose combination-NA/EE 0.5 mg/2.5 microg-in the treatment of postmenopausal symptoms, based on data from previously published studies of NA/EE. In addition, the effects of low-dose NA/EE on bone and endometrium are briefly reviewed. METHODS: Data from 3 previously published randomized, placebo-controlled trials were analyzed using current FDA guidance for the assessment of HT in postmenopausal women. Studies 1 and 2 assessed the efficacy of NA/EE at various doses, including 0.5 mg/2.5 microg, in vasomotor symptom (hot-flush [HF]) relief over 16 and 12 weeks, respectively, using self-reporting of symptom frequency and intensity (scores: 0=none; 1=mild; 2=moderate; and 3=severe) in daily diaries. Study 3 assessed the effects of NA/EE at various doses, including 0.5 mg/2.5 microg, on bone and endometrium, using quantitative computed tomography of the lumbar spine at 12 and 24 months and endometrial biopsy at 6, 12, 18, and 24 months of treatment. In all 3 studies, women were asked to record vaginal bleeding and spotting in diaries. Any adverse events were recorded in diaries and/or at clinic visits. Physical and gynecologic examinations and standard clinical laboratory testing were conducted at baseline and at appropriate follow-up visits in all 3 studies. RESULTS: Studies 1, 2, and 3 enrolled 219, 266, and 1265 women, respectively. Overall, in studies 1 and 2, 91% of women were white, the mean age was approximately 52 years, and mean time since last menstrual period was approximately 24 months. In study 1, NA/EE 0.5 mg/2.5 microg was associated with significant reductions from baseline in mean weekly total HF frequency from week 4 (63.6%) through week 16 (73.7%) (all, P<0.05). In study 2, the frequency of moderate or severe HFs was decreased by 61.1% at week 4 (P<0.05) and by 82.2% at week 12 (P<0.001) with NA/EE 0.5 mg/2.5 microg, and the mean intensity score was significantly lower than that with placebo at weeks 8 and 12 (both, P=0.001). In study 3, cumulative amenorrhea rates were approximately 90% in the NA/EE 0.5-mg/2.5-microg and placebo groups at 12 months. Lumbar spine bone mineral density (BMD) was maintained at 24 months with NA/EE 0.5 mg/2.5 microg but was significantly decreased from baseline, by 7.4%, in the placebo group (P<0.001). Endometrial hyperplasia was not observed in the group receiving NA/EE 0.5 mg/2.5 microg over 24 months. The tolerability of NA/EE was similar to that of placebo. The most common adverse events experienced with NA/EE were headache (15.2%), abdominal pain (10.2%), and breast pain (9.0%). CONCLUSIONS: The results from this post hoc analysis and overview of 3 previously published studies suggest that NA/EE 0.5 mg/2.5 microg was associated with decreased frequency and intensity of vasomotor symptoms. This dose of NA/EE was also associated with maintenance of BMD over 24 months, a significant positive effect on BMD compared with placebo. Low-dose NA/EE was also associated with cumulative amenorrhea rates comparable to those of placebo and was not associated with endometrial hyperplasia. This dose was well tolerated, with rates of adverse events generally similar to those of placebo.

Bone Density↗
PubMed2006

Skeletal consequences of hormone therapy discontinuance: a systematic review.

UNLABELLED: Although hormone therapy protects against bone loss after menopause, currently it is not recommended once menopausal symptoms have subsided. We reviewed randomized clinical trials to quantify bone loss after stopping hormone therapy and summarize treatment options for women who discontinue hormone treatment. We conducted a search of MEDLINE and EMBASE for randomized, controlled trials measuring bone mineral density (BMD) after hormone therapy discontinuation. Other known published and unpublished data were also included. Eleven studies fulfilled the search criteria. In each, bone loss was rapid after stopping hormone therapy, with BMD declines ranging from 2.3% to 6.2% in the first year. Increases in bone turnover markers also occurred rapidly when hormone therapy was stopped. Limited data addressing treatment after hormone therapy is stopped exist; only 2 studies specifically evaluated therapy to protect bone after hormone discontinuation. Taken together, these 2 studies demonstrate that alendronate produced significant increases relative to placebo in spine, hip, and total body BMD in women with low bone density who had discontinued hormone therapy within the past 3 months, preventing the rapid bone loss seen on discontinuation of hormone therapy. Among treatment options for preventing bone loss on discontinuation of hormone therapy for which randomized clinical trial data are available, alendronate prevented bone loss or increased bone density in postmenopausal women with low bone density. Women who are discontinuing hormone therapy should be counseled about potential bone loss and effective treatment options. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader should be able to state that discontinuation of replacement menopausal hormone therapy, which protects against bone loss, is not recommended after menopause symptoms have subsided; recall that it may accelerate bone loss; and explain that there is bone loss preventive treatment for women after discontinuation of hormone therapy.

Aged↗
PubMed2005

Does osteopenia warrant treatment?

The progressive loss of bone mass that leads to osteoporosis in postmenopausal women is known to result in substantial morbidity and mortality. Underdiagnosed and undertreated, osteoporosis jeopardizes the health of an estimated 8 million American women 50 years of age or older who are at high risk for hip, vertebral, and other fractures. Because osteopenia is generally a subclinical condition that results in a lower fracture rate than osteoporosis, its potential impact is more difficult to recognize, although it is nearly three times more prevalent than osteoporosis. The question arises as to whether osteopenia should be diagnosed and treated before it transitions into osteoporosis. Because the number of postmenopausal women is projected to increase substantially in the near future and the number of postmenopausal women who will or who have discontinued their use of hormone therapy has increased sharply, the consequences of failing to identify and treat women at increased fracture risk are considerable. Moreover, the rate of bone loss in the first year after discontinuation of hormone therapy is especially rapid and similar to the rate that occurs early after menopause. Accordingly, fracture risk is substantially increased at this time in relation to the magnitude of bone loss. The goal of nonpharmacologic and pharmacologic therapy is to prevent the first fracture in any woman at risk for fracture. Initiation of antiresorptive therapy known to provide rapid efficacy can be particularly important in achieving the treatment goal in appropriate osteopenic women.

Female↗
PubMed2005

Monitoring reproductive aging in a 5-year prospective study: aggregate and individual changes in steroid hormones and menstrual cycle lengths with age.

OBJECTIVE: We describe a 5-year prospective study of reproductive aging, and present analyses of steroid hormone and menstrual cycle changes with age. DESIGN: Participants were college-educated white women, primarily of northern European ancestry, recruited from the Tremin Research Program on Women's Health (n = 156, 25-58 years). In each of 5 consecutive years, they collected daily urine specimens for 6 months and recorded menstrual bleeds for all months. Urine specimens were assayed for estrone-3-glucuronide (E1G) and pregnanediol-3-glucuronide (PDG), urinary metabolites of estradiol and progesterone. Using multilevel models, we estimated hormone and cycle-length trajectories for individual women and within- and between-woman variance by age. RESULTS: At the aggregate level, PDG declined beginning in the 30s, E1G increased into the 40s before declining, and cycle length became more variable with age. Individual-level models revealed substantial hormonal variation across women, in both absolute levels and rates of change. Most women showed declining E1G by the late 40s, declining PDG in the 30s, and increasing mean cycle length in the 40s. Hormonal variation decreased with age; cycle length variation decreased and then increased. Within individual women, cycle lengths were highly variable while hormone levels were more stable. Women differed more from each other in hormone levels than for cycle lengths. CONCLUSIONS: Aggregate-level analyses show general changes in steroid hormones and cycle length but cannot show variation within and across women. Individuals' cycle lengths were too variable to predict hormone levels. Clinicians should obtain more data on individual women's hormonal patterns when determining fertility or menopause treatments.

Adult↗
PubMed2005

Safety and efficacy of a testosterone patch for the treatment of hypoactive sexual desire disorder in surgically menopausal women: a randomized, placebo-controlled trial.

BACKGROUND: Oophorectomy reduces serum testosterone levels. We studied the efficacy and safety of transdermal testosterone in treating hypoactive sexual desire disorder in surgically menopausal women. METHODS: A 24-week, randomized, double-blind, placebo-controlled, parallel-group, multicenter trial was conducted in women (aged 24-70 years) who developed distressful low sexual desire after bilateral salpingo-oophorectomy and hysterectomy and who were receiving oral estrogen therapy. Women were randomized to receive placebo (n = 119) or testosterone patches in dosages of 150 microg/d (n = 107), 300 microg/d (n = 110), or 450 microg/d (n = 111) twice weekly for 24 weeks. Sexual desire and frequency of satisfying sexual activity were primary efficacy outcome measures. RESULTS: Of the 447 women randomized, 318 (71%) completed the trial. Compared with placebo, women receiving the 300-microg/d testosterone patch had significantly greater increases from baseline in sexual desire (67% vs 48%; P = .05) and in frequency of satisfying sexual activity (79% vs 43%; P = .049). The 150-microg/d group showed no evidence of a treatment effect. The 450-microg/d group also was not statistically different from the 300-microg/d or placebo groups. Marginally significant linear dose-response trends were observed for total satisfying sexual activity and sexual desire at 24 weeks (P = .06 and .06, respectively). Adverse events occurred with similar frequency in both groups; no serious safety concerns were observed. CONCLUSIONS: The 300-microg/d testosterone patch increased sexual desire and frequency of satisfying sexual activity and was well tolerated in women who developed hypoactive sexual desire disorder after surgical menopause.

Administration, Cutaneous↗
PubMed2004

In vitro effect of gonadotropin-releasing hormone agonist on natural killer cell cytolysis in women with and without endometriosis.

OBJECTIVE: The purpose of this study was to assess the in vitro effect of gonadotropin-releasing hormone agonist on natural killer cell activity in women with and without endometriosis and to ascertain whether gonadotropin-releasing hormone agonist effects on natural killer cell activity are direct or mediated solely through the hypoestrogenic state that they produce in vivo. STUDY DESIGN: With use of a chromium 51 release microcytotoxicity assay with K562 target cells, natural killer cell activity was measured after the incubation of mononuclear cells with leuprolide acetate that was obtained from 16 patients with endometriosis and 11 control subjects. RESULTS: The cytotoxicity of natural killer cells that were obtained from patients with endometriosis was reduced significantly (P<.001) with leuprolide. Natural killer cell cytotoxicity from control patients was also significantly decreased (P=.005) with gonadotropin-releasing hormone agonist. Natural killer cell cytotoxicity was significantly lower in patients with endometriosis than in control patients (P=.029). CONCLUSION: These findings suggest a direct immunomodulatory role of gonadotropin-releasing hormone agonist on natural killer cell activity and confirm previous findings that patients with endometriosis have reduced natural killer cell cytotoxicity.

Adjuvants, Immunologic↗
PubMed2003

Prevention and management of osteoporosis.

Osteoporotic fractures are a growing public health issue. Prevention and management of osteoporosis are becoming increasing concerns especially as the number of individuals reaching old age continues to grow, euphemistically "as the baby boomers come of age." Identification of those individuals who are at an increased risk for fracture is important for planning and implementing proper prevention and management strategies. Although diagnostic tools are available for identifying decreased bone density and effective therapies exist for treatment of existing disease, clinical guidelines based on cost-effective approaches are still needed to more accurately identify which patients would benefit from early intervention (either prevention or treatment).

Calcitonin↗
PubMed2003

Reduced vaginal bleeding in postmenopausal women who receive combined norethindrone acetate and low-dose ethinyl estradiol therapy versus combined conjugated equine estrogens and medroxyprogesterone acetate therapy.

OBJECTIVE: The purpose of this study was to compare the effects on vaginal bleeding patterns of continuous combined hormone replacement therapy with norethindrone acetate and ethinyl estradiol versus conjugated equine estrogens and medroxyprogesterone acetate. STUDY DESIGN: Three hundred fifty-seven postmenopausal women were selected randomly (in a blinded manner) to 12 months of treatment with 1 mg norethindrone acetate/5 microg ethinyl estradiol, placebo, or open-label 0.625 mg conjugated equine estrogens/2.5 mg medroxyprogesterone acetate (conjugated equine estrogens/medroxyprogesterone acetate [CEE/MPA]; Prempro). The incidence and duration of vaginal bleeding were assessed throughout the study. Statistical analyses used Cochran-Mantel-Haenszel methodology and analysis of variance. RESULTS: At 3 months, 1 mg norethindrone acetate/5 microg ethinyl estradiol therapy reduced the incidence of bleeding (12% vs 23%; P <.029) and bleeding and/or spotting (22% vs 44%; P <.001), compared with conjugated equine estrogens/medroxyprogesterone acetate therapy. The mean duration of bleeding and bleeding and/or spotting were also reduced with 1 mg norethindrone acetate/5 microg ethinyl estradiol therapy versus conjugated equine estrogens/medroxyprogesterone acetate (P =.004 and P <.001, respectively). The incidence of cumulative amenorrhea at every monthly interval was significantly better with 1 mg norethindrone acetate/5 microg ethinyl estradiol therapy versus conjugated equine estrogens/medroxyprogesterone acetate therapy (P <.05). Associated adverse event (ie, headache, breast pain) incidence rates were similar in the 2 active treatment groups. CONCLUSION: The 1 mg norethindrone acetate/5 microg ethinyl estradiol therapy provides significantly better control of vaginal bleeding than conjugated equine estrogens/medroxyprogesterone acetate therapy at all time points investigated in this 12-month study.

Adult↗
PubMed2002

Estrogen replacement therapy: effects on the endogenous androgen milieu.

OBJECTIVE: To review the impact of exogenous estrogen replacement therapy (ERT) on the production, binding, and metabolism of ovarian and adrenal androgens. DESIGN: Review of the scientific literature from January 1966 through June 2001 using MEDLINE. CONCLUSION(S): Although no precipitous drop in androgen production is apparent at the time of the menopause, androgens decrease slowly and progressively from early adulthood until old age. The impact of aging and of estrogen replacement therapy, particularly oral ERT, significantly reduces androgen bioavailability after menopause. The combined effects of reduced production with aging and the pharmacologic effects of oral ERT dramatically reduce the endogenous bioavailable androgen milieu. These changes may have adverse clinical implications for susceptible individuals.

Adrenal Glands↗
PubMed2002

Patient preference for once-weekly alendronate 70 mg versus once-daily alendronate 10 mg: a multicenter, randomized, open-label, crossover study.

BACKGROUND: Alendronate, an oral bisphosphonate, is available for the treatment of osteoporosis in a 70-mg once-weekly and a 10-mg once-daily formulation. OBJECTIVES: This study aimed to determine patient preference for once-weekly versus once-daily dosing with alendronate, and to determine which treatment regimen the patients believed was more convenient and would be easier to comply with for a long period. METHODS: This was a multicenter, randomized, open-label, preference study in which postmenopausal women with osteoporosis were enrolled to receive 9 weeks of treatment in crossover fashion (4 weeks with each study regimen separated by a 1-week washout period). The study regimens included once-weekly alendronate 70 mg and once-daily alendronate 10 mg. The primary and secondary end points were assessed with a questionnaire completed by the patient. Adverse events (AEs) were recorded to assess patient tolerability of the study medications. RESULTS: A total of 324 patients met the eligibility requirements; 288 were randomized to treatment, 287 (mean age, 64.8 years) received treatment, 272 completed the questionnaire, and 266 completed the study. Of the patients who completed the questionnaire, 235 patients preferred the 70-mg once-weekly dosing regimen compared with the 10-mg once-daily regimen (86.4% vs 9.2%; P < 0.001). Most patients also believed that once-weekly dosing was more convenient than once-daily dosing (89.0% vs 7.7%; P < 0.001) and would allow them to achieve better long-term compliance (87.5% vs 8.5%; P < 0.001). Clinical AEs were reported in 30.7% of patients treated with once-weekly alendronate and 30% of patients treated with once-daily alendronate, with no significant differences between treatments. CONCLUSION: When once-weekly alendronate 70 mg was compared with once-daily alendronate 10 mg in this study, 70-mg once-weekly alendronate was the preferred dosing regimen.

Administration, Oral↗
PubMedDate not supplied

Maximizing health in menopausal women with disabilities.

There are nearly 30 million women with disabilities in the United States. Of these, more than 16 million are over the age of 50. Years ago, women with disabilities did not commonly live to the age of menopause, and, if they did, they reached this stage of life in a very debilitated condition. Now, women with disabilities are entering their mature years as active members of society who can look forward to productive futures. Because the health needs of women with disabilities might differ from those of other women, special attention should be focused on how physiological changes of perimenopausal and menopausal states affect this population. In addition to functional changes that might affect menopausal women with disabilities, basic health maintenance issues may be adversely affected by environmental factors. Physical barriers can influence compliance with preventive health screening that is essential in aging populations. Treatment options might need to be tailored to the individual. The disabling condition itself may progress, resulting in secondary conditions requiring creative interventions. A comprehensive evaluation and the development of a suitable management plan, which takes into account the multifactorial nature of aging as a disabled woman, are essential in delivering optimal care to this population.

Adult↗
PubMedDate not supplied

A comparison of therapy continuation rates of different hormone replacement agents: a 9-month retrospective, longitudinal analysis of pharmacy claims among new users.

OBJECTIVE: To estimate the rate of therapy continuation among women using six different hormone replacement therapies (HRTs). DESIGN: A retrospective, longitudinal analysis of pharmacy claims data was conducted for 7,120 women who were new users of six HRT regimens. Continuation rates of therapies were examined at the end of the 9-month period. In addition, the odds ratio of continuation for each product was determined using a logistic model, which controlled for the potential influence of a patient's age and a provider's age, gender, specialty, and geographical location. RESULTS: Treatment continuation rates at the end of the 9-month period were significantly higher among patients prescribed oral 1 mg norethindrone acetate/5 microgram ethinyl estradiol (EE) (femhrt, Pfizer Inc, New York, NY, USA) compared with other HRT regimens. Patients prescribed 1 mg norethindrone acetate/5 microgram EE were 52% more likely to continue therapy compared with patients prescribed 0.625 mg conjugated equine estrogens/2.5 mg or 5 mg medroxyprogesterone acetate (Prempro, Wyeth, Madison, NJ, USA). Significantly higher rates of therapy continuation were seen in women aged 55 years or older, those who did not switch HRT during the analysis, those who received care in the central and northeast regions of the United States, and those who were seen by obstetricians/gynecologists (v primary care physicians) or female (v male) providers. CONCLUSIONS: The higher rates of treatment continuation seen with newer continuous combined HRTs, such as 1 mg norethindrone acetate/5 microgram EE, may lead to improved long-term compliance and, therefore, better protection against osteoporosis in postmenopausal women.

Adolescent↗
PubMedDate not supplied

A cost-effectiveness evaluation of two continuous-combined hormone therapies for the management of moderate-to-severe vasomotor symptoms.

OBJECTIVES: After the release of the results of the Women's Health Initiative, an emerging consensus suggests that continuous-combined hormone therapy (CCHT) should be limited to short-term management of moderate-to-severe vasomotor symptoms. This, in turn, raises the important question of the economic value, if any, of short-term CCHT for this indication. We conducted a cost-effectiveness analysis comparing a 1-year treatment course with 1 mg of norethindrone acetate/5 microg of ethinyl estradiol (1/5 NA/EE) or 0.625 mg/day of conjugated estrogens plus 2.5 mg of medroxyprogesterone (0.625/2.5 CEE/MPA) compared with no therapy for the management of moderate-to-severe vasomotor symptoms. DESIGN: A literature-based Markov model was developed to compare these three options' cost and quality-of-life (QOL) benefits. The impact of therapy on vasomotor symptoms and breakthrough bleeding/spotting on the direct costs of care and QOL were considered. RESULTS: Compared with no therapy, CCHTs resulted in net increases in quality-adjusted life-years (QALYs) gained (0.110 for 1/5 NA/NE v 0.104 for 0.625/2.5 CEE/MPA). Net costs (v no therapy) were $167 lower for 1/5 NA/NE compared with 0.625/2.5 CEE/MPA. Cost per QALY gained (compared with no therapy) were $6,200 and $8,200, respectively. Cost-effectiveness was most favorable for individuals with more severe symptoms who were less bothered by breakthrough bleeding/spotting. CONCLUSIONS: A short-term course of CCHT for the sole purpose of managing moderate-to-severe vasomotor symptoms is cost-effective. However, 1/5 NA/NE seemed to be more cost-effective than 0.625/2.5 CEE/MPA. These findings can be used to further refine the role of CCHT and to improve formulary decisions.

Cost-Benefit Analysis↗
PubMedDate not supplied

Estradiol in micellar nanoparticles: the efficacy and safety of a novel transdermal drug-delivery technology in the management of moderate to severe vasomotor symptoms.

OBJECTIVE: To assess the efficacy and safety of topical micellar nanoparticle estradiol emulsion (MNPEE; Estrasorb; Novavax, Inc., Malvern, PA) in postmenopausal women with moderate to severe vasomotor symptoms. DESIGN: A multicenter, randomized, double-blind, placebo-controlled study was conducted in 200 postmenopausal women with seven or more moderate to severe hot flushes per day. The study consisted of a 3-week screening period followed by a 1-week placebo emulsion run-in period and a 12-week active or placebo treatment period. Women were randomized (1:1) to receive MNPEE (3.45 g daily dose of emulsion containing 8.6 mg estradiol) or matching placebo emulsion. The primary efficacy variable was the change from baseline in the frequency of moderate and severe hot flushes at weeks 4 and 12. Adverse events were monitored throughout the trial. RESULTS: Topical micellar nanoparticle estradiol emulsion was statistically significantly superior to placebo emulsion in reducing the mean frequency of moderate to severe vasomotor symptoms by week 3 (P = 0.003), with superiority to placebo maintained from weeks 4 to 12 (P < 0.001). At week 12 (peak benefit), MNPEE reduced mean daily frequency of hot flush count by 11.1 (P < 0.001 vs placebo). MNPEE significantly reduced mean symptom severity from weeks 4 to 12 (P < 0.001) compared with placebo. At endpoint, mean serum concentrations of estradiol and estrone were 63 and 89 pg/mL, respectively, in the MNPEE group. The mean endpoint ratio of estradiol to estrone in these patients was 0.774. MNPEE was safe and well tolerated. CONCLUSION: Once-daily application of 3.45 g of micellar nanoparticle estradiol emulsion containing 8.6 mg of estradiol was safe and effective in providing significant relief of vasomotor symptom frequency and severity in postmenopausal women.

Administration, Cutaneous↗
PubMedDate not supplied

Lifelong menstrual histories are typically erratic and trending: a taxonomy.

OBJECTIVE: Menstrual cycles are composites of complex events; the data describing them are correspondingly rich. We seek to quantitatively represent menstrual histories from menarche to menopause and to evaluate the clinical belief that regular and stable cycle lengths are the most normative histories. DESIGN: Using prospective data from the Tremin Trust, we classified the menstrual histories of 628 women as very stable (type I), stable but with greater variability in cycle lengths (type II), oscillating and erratic with a downward trend in cycle length (type III), oscillating and erratic with no downward trend in cycle length (type IV), or highly erratic and variable (type V). Classification criteria were created by examining basic summary statistics of menstrual cycle lengths. Specifically, we identified key features describing variability of median cycle length, the mean of the interquartile range, the consistency of the interquartile range, the slope of median cycle lengths, and the number of stable 5-year intervals between ages 15 and 45+. RESULTS: We present the first characterization of full menstrual histories. Our taxonomy captures the essential features of menstrual bleeding patterns for a heterogeneous population. Persistently stable histories (types I and II) were seen in only 28% of the women; erratic histories (types III through V) characterized 72%. When examining all participants, significant differences were seen in age at menarche (P < 0.05), age at menopause (P < 0.01), and number of births (P < 0.01) between these stable and erratic groups. CONCLUSIONS: Although clinicians have traditionally thought of "normal" menstrual histories as being regular and stable, the distribution of women in our five categories suggest that variable histories are most common. Clinically, these results may suggest the need for a paradigm shift in what gynecologists view as normal and abnormal menstrual cycle histories.

Algorithms↗