The cost-effectiveness of progesterone in preventing miscarriages in women with early pregnancy bleeding: an economic evaluation based on the PRISM trial.

OBJECTIVES: To assess the cost-effectiveness of progesterone compared with placebo in preventing pregnancy loss in women with early pregnancy vaginal bleeding. DESIGN: Economic evaluation alongside a large multi-centre randomised placebo-controlled trial. SETTING: Forty-eight UK NHS early pregnancy units. POPULATION: Four thousand one hundred and fifty-three women aged 16-39 years with bleeding in early pregnancy and ultrasound evidence of an intrauterine sac. METHODS: An incremental cost-effectiveness analysis was performed from National Health Service (NHS) and NHS and Personal Social Services perspectives. Subgroup analyses were carried out on women with one or more and three or more previous miscarriages. MAIN OUTCOME MEASURES: Cost per additional live birth at ≥34 weeks of gestation. RESULTS: Progesterone intervention led to an effect difference of 0.022 (95% CI -0.004 to 0.050) in the trial. The mean cost per woman in the progesterone group was £76 (95% CI -£559 to £711) more than the mean cost in the placebo group. The incremental cost-effectiveness ratio for progesterone compared with placebo was £3305 per additional live birth. For women with at least one previous miscarriage, progesterone was more effective than placebo with an effect difference of 0.055 (95% CI 0.014-0.096) and this was associated with a cost saving of £322 (95% CI -£1318 to £673). CONCLUSIONS: The results suggest that progesterone is associated with a small positive impact and a small additional cost. Both subgroup analyses were more favourable, especially for women who had one or more previous miscarriages. Given available evidence, progesterone is likely to be a cost-effective intervention, particularly for women with previous miscarriage(s). TWEETABLE ABSTRACT: Progesterone treatment is likely to be cost-effective in women with early pregnancy bleeding and a history of miscarriage.

Cervical pessary vs vaginal progesterone for prevention of preterm birth in women with twin pregnancy and short cervix: economic analysis following randomized controlled trial.

OBJECTIVE: To compare the cost-effectiveness of cervical pessary vs vaginal progesterone to prevent preterm birth and neonatal morbidity in women with twin pregnancy and a short cervix. METHODS: Between 4 March 2016 and 3 June 2017, we performed this economic analysis following a randomized controlled trial (RCT), performed at My Duc Hospital, Ho Chi Minh City, Vietnam, that compared cervical pessary to vaginal progesterone in women with twin pregnancy and cervical length < 38 mm between 16 and 22 weeks of gestation. We used morbidity-free neonatal survival as a measure of effectiveness. Data on pregnancy outcome, maternal morbidity and neonatal complications were collected prospectively from medical files; additional information was obtained via telephone interviews with the patients. The incremental cost-effectiveness ratio was calculated as the incremental cost required to achieve one extra surviving morbidity-free neonate in the pessary group compared with in the progesterone group. Probabilistic and one-way sensitivity analyses were also performed. RESULTS: During the study period, we screened 1113 women with twin pregnancy, of whom 300 fulfilled the inclusion criteria of the RCT and gave informed consent to participate. These women were assigned randomly to receive cervical pessary (n = 150) or vaginal progesterone (n = 150), with two women and one woman, respectively, being lost to follow-up. The rate of morbidity-free neonatal survival was significantly higher in the pessary group compared with the progesterone group (n = 241/296 (81.4%) vs 219/298 (73.5%); relative risk, 1.11 (95% CI, 1.02-1.21), P = 0.02). The mean total cost per woman was 3146 € in the pessary group vs 3570 € in the progesterone group (absolute difference, -424 € (95% CI, -842 to -3 €), P = 0.048). The cost per morbidity-free neonate was significantly lower in the pessary group compared with that in the progesterone group (2492 vs 2639 €; absolute difference, -147 € (95% CI, -284 to 10 €), P = 0.035). CONCLUSION: In women with twin pregnancy and a short cervix, cervical pessary improves significantly the rate of morbidity-free neonatal survival while reducing costs, as compared with vaginal progesterone. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Evaluation of Progesterone Utilization and Birth Outcomes in a State Medicaid Plan.

OBJECTIVES: Progesterone (hydroxyprogesterone caproate injection and vaginal progesterone) has been shown to reduce preterm birth (PTB) rates by a third among pregnant women at high risk. The purpose of this analysis is to report birth outcomes and medication adherence among Massachusetts Medicaid (MassHealth) members receiving progesterone, evaluate the association between member characteristics and birth outcomes and medication adherence, and compare cost of care with a prior preterm pregnancy. METHODS: This retrospective cohort study used medical claims, pharmacy claims, and prior authorization (PA) request data for MassHealth members who had a PA submitted for progesterone between January 1, 2011, and March 31, 2015. Members were excluded due to breaks in coverage, progesterone was not indicated for prevention of PTB, and if current gestational week or date of delivery was unavailable. MAIN RESULTS: A total of 418 members were screened for inclusion of whom 190 met criteria and 169 filled progesterone. Mean age was 29.2 years (SD = 5.23), and clinical comorbidities were identified in 90.5% of members. Consistent with clinical trials on progesterone effectiveness, 62.1% of members had a term delivery (37 wks of gestation). Among members with prior gestational age at delivery available, the average difference in gestational age between pregnancies was 8.25 weeks (SD = 6.11). In addition, 66.3% of members were adherent to progesterone based on proportion of days covered (PDC) of 0.8 or higher. The overall mean PDC was 0.79 (SD = 0.26). CONCLUSION: Despite similar birth outcomes in clinical trials and national trends, medication adherence is low in this state Medicaid program. Therefore, members may benefit from adherence support.

Variation in Coverage for Progesterone to Prevent Preterm Birth: A Survey of Medicaid Managed Care Organizations.

INTRODUCTION: Preterm birth is the leading cause of U.S. infant morbidity and mortality; Medicaid enrollees disproportionately experience preterm deliveries. Data suggest that progesterone-an evidence-based therapy for preventing preterm birth-is not accessible to all eligible Medicaid beneficiaries. This study aimed to identify variation in progesterone coverage guidelines in a sample of state Medicaid managed care organizations (MMCOs). MATERIAL AND METHODS: Using a cross-sectional design, participation in a web-based survey was offered to 20 MMCO members of the Medicaid Health Plans of America. The survey assessed coverage guidelines for progesterone and associated interventions to prevent preterm birth. MMCOs identified key barriers in providing progesterone. Descriptive analyses were performed. RESULTS: Analyses included data from 18 plans providing coverage in 31 of the 39 states with MMCOs (response rate, 90.0%). Responding MMCOs were diverse: 55.6% were multistate, 33.3% were nonprofit, and 31.2% covered more than 1,000,000 lives. Most respondents (87.5%) covered branded progesterone, and 81.3% covered compounded progesterone. Prior authorization was required by most plans for branded progesterone (86.7%) or compounded progesterone (75.0%). The MMCO gestational age restrictions for initiating progesterone varied from 22 to 37 weeks of gestation, even within the same state. MMCO-identified barriers to providing progesterone included cost, lack of clinician knowledge of indications and coverage, and variation in billing procedures. DISCUSSION: Marked variation in MMCO coverage policies and procedures for progesterone and related interventions to prevent preterm birth was noted. IMPLICATIONS FOR PRACTICE AND POLICY: Standardizing MMCO coverage policies may be one way to improve access to evidence-based interventions that prevent preterm birth.

PROMISE: first-trimester progesterone therapy in women with a history of unexplained recurrent miscarriages - a randomised, double-blind, placebo-controlled, international multicentre trial and economic evaluation.

BACKGROUND AND OBJECTIVES: Progesterone is essential to maintain a healthy pregnancy. Guidance from the Royal College of Obstetricians and Gynaecologists and a Cochrane review called for a definitive trial to test whether or not progesterone therapy in the first trimester could reduce the risk of miscarriage in women with a history of unexplained recurrent miscarriage (RM). The PROMISE trial was conducted to answer this question. A concurrent cost-effectiveness analysis was conducted. DESIGN AND SETTING: A randomised, double-blind, placebo-controlled, international multicentre study, with economic evaluation, conducted in hospital settings across the UK (36 sites) and in the Netherlands (nine sites). PARTICIPANTS AND INTERVENTIONS: Women with unexplained RM (three or more first-trimester losses), aged between 18 and 39 years at randomisation, conceiving naturally and giving informed consent, received either micronised progesterone (Utrogestan(®), Besins Healthcare) at a dose of 400 mg (two vaginal capsules of 200 mg) or placebo vaginal capsules twice daily, administered vaginally from soon after a positive urinary pregnancy test (and no later than 6 weeks of gestation) until 12 completed weeks of gestation (or earlier if the pregnancy ended before 12 weeks). MAIN OUTCOME MEASURES: Live birth beyond 24 completed weeks of gestation (primary outcome), clinical pregnancy at 6-8 weeks, ongoing pregnancy at 12 weeks, miscarriage, gestation at delivery, neonatal survival at 28 days of life, congenital abnormalities and resource use. METHODS: Participants were randomised after confirmation of pregnancy. Randomisation was performed online via a secure internet facility. Data were collected on four occasions of outcome assessment after randomisation, up to 28 days after birth. RESULTS: A total of 1568 participants were screened for eligibility. Of the 836 women randomised between 2010 and 2013, 404 received progesterone and 432 received placebo. The baseline data (age, body mass index, maternal ethnicity, smoking status and parity) of the participants were comparable in the two arms of the trial. The follow-up rate to primary outcome was 826 out of 836 (98.8%). The live birth rate in the progesterone group was 65.8% (262/398) and in the placebo group it was 63.3% (271/428), giving a relative risk of 1.04 (95% confidence interval 0.94 to 1.15; p = 0.45). There was no evidence of a significant difference between the groups for any of the secondary outcomes. Economic analysis suggested a favourable incremental cost-effectiveness ratio for decision-making but wide confidence intervals indicated a high level of uncertainty in the health benefits. Additional sensitivity analysis suggested the probability that progesterone would fall within the National Institute for Health and Care Excellence's threshold of £20,000-30,000 per quality-adjusted life-year as between 0.7145 and 0.7341. CONCLUSIONS: There is no evidence that first-trimester progesterone therapy improves outcomes in women with a history of unexplained RM. LIMITATIONS: This study did not explore the effect of treatment with other progesterone preparations or treatment during the luteal phase of the menstrual cycle. FUTURE WORK: Future research could explore the efficacy of progesterone supplementation administered during the luteal phase of the menstrual cycle in women attempting natural conception despite a history of RM. TRIAL REGISTRATION: Current Controlled Trials ISRCTN92644181; EudraCT 2009-011208-42; Research Ethics Committee 09/H1208/44. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 41. See the NIHR Journals Library website for further project information.

Peri-operative biology in primary breast cancer: a credible therapeutic target.

Over the last 25 years, there has been a growing body of basic science, modeling, and clinical data suggesting that the peri-operative period in the treatment of primary breast cancer is dynamic and can be manipulated to improve long-term outcomes. Clinical data have demonstrated early peaks of hazards for recurrence and emphasized the relationship of these to peri-operative events. More recently, clinical trial data with surgical oophorectomy at different times in the menstrual cycle, peri-operative progesterone, and anti-inflammatory drugs suggest that interventional studies are particularly well justified, given the increasing recognition of the costs both financially and clinically of current systemic regimens.

Revisiting the cost-effectiveness of universal cervical length screening: importance of progesterone efficacy.

BACKGROUND: Preterm birth (PTB) is a significant cause of neonatal morbidity and mortality. Studies have shown that vaginal progesterone therapy for women diagnosed with shortened cervical length can reduce the risk of PTB. However, published cost-effectiveness analyses of vaginal progesterone for short cervix have not considered an appropriate range of clinically important parameters. OBJECTIVE: To evaluate the cost-effectiveness of universal cervical length screening in women without a history of spontaneous PTB, assuming that all women with shortened cervical length receive progesterone to reduce the likelihood of PTB. STUDY DESIGN: A decision analysis model was developed to compare universal screening and no-screening strategies. The primary outcome was the cost-effectiveness ratio of both the strategies, defined as the estimated patient cost per quality-adjusted life-year (QALY) realized by the children. One-way sensitivity analyses were performed by varying progesterone efficacy to prevent PTB. A probabilistic sensitivity analysis was performed to address uncertainties in model parameter estimates. RESULTS: In our base-case analysis, assuming that progesterone reduces the likelihood of PTB by 11%, the incremental cost-effectiveness ratio for screening was $158,000/QALY. Sensitivity analyses show that these results are highly sensitive to the presumed efficacy of progesterone to prevent PTB. In a 1-way sensitivity analysis, screening results in cost-saving if progesterone can reduce PTB by 36%. Additionally, for screening to be cost-effective at WTP=$60,000 in three clinical scenarios, progesterone therapy has to reduce PTB by 60%, 34% and 93%. Screening is never cost-saving in the worst-case scenario or when serial ultrasounds are employed, but could be cost-saving with a two-day hospitalization only if progesterone were 64% effective. CONCLUSION: Cervical length screening and treatment with progesterone is a not a dominant, cost-effective strategy unless progesterone is more effective than has been suggested by available data for US women. Until future trials demonstrate greater progesterone efficacy, and effectiveness studies confirm a benefit from screening and treatment, the cost-effectiveness of universal cervical length screening in the United States remains questionable.

Pros and cons of maternal cervical length screening to identify women at risk of spontaneous preterm delivery.

Large randomized controlled trials have demonstrated that universal maternal cervical length screening and treatment with daily vaginal progesterone in women with short cervical length reduces the risk of preterm birth, but large numbers of women must be screened to prevent a relatively small number of preterm deliveries. Issues that should be considered while implementing universal cervical length screening include: (1) the standards of quality and reproducibility for transvaginal ultrasound cervical length ascertainment; and (2) the implications of screening on the application of therapeutic strategies to populations not known to benefit (so-called "indication creep"). Optimal strategies to employ cervical ultrasound and progesterone treatment might be revealed by additional studies investigating cervical length cutoffs, frequency of screening, selective screening in higher-risk groups, and the use of transabdominal cervical length screening as a surrogate for transvaginal cervical length screening.

Cost and cost effectiveness of vaginal progesterone gel in reducing preterm birth: an economic analysis of the PREGNANT trial.

BACKGROUND: Preterm birth (PTB) is a costly public health problem in the USA. The PREGNANT trial tested the efficacy of vaginal progesterone (VP) 8 % gel in reducing the likelihood of PTB among women with a short cervix. OBJECTIVE: We calculated the costs and cost effectiveness of VP gel versus placebo using decision analytic models informed by PREGNANT patient-level data. METHODS: PREGNANT enrolled 459 pregnant women with a cervical length of 10-20 mm and randomized them to either VP 8 % gel or placebo. We used a cost model to estimate the total cost of treatment per mother and a cost-effectiveness model to estimate the cost per PTB averted with VP gel versus placebo. Patient-level trial data informed model inputs and included PTB rates in low- and high-risk women in each study group at <28 weeks gestation, 28-31, 32-36, and ≥37 weeks. Cost assumptions were based on 2010 US healthcare services reimbursements. The cost model was validated against patient-level data. Sensitivity analyses were used to test the robustness of the cost-effectiveness model. RESULTS: The estimated cost per mother was $US23,079 for VP gel and $US36,436 for placebo. The cost-effectiveness model showed savings of $US24,071 per PTB averted with VP gel. VP gel realized cost savings and cost effectiveness in 79 % of simulations. CONCLUSION: Based on findings from PREGNANT, VP gel was associated with cost savings and cost effectiveness compared with placebo. Future trials designed to include cost metrics are needed to better understand the value of VP.

Cryo-thawed embryo transfer: natural versus artificial cycle. A non-inferiority trial. (ANTARCTICA trial).

BACKGROUND: Frozen thawed embryo transfer (FET) is a cost-effective adjunct to IVF or IVF-ICSI treatment. In order to optimize treatment outcome, FET should be carried out during a period of optimal endometrial receptivity. To optimize implantation several methods for endometrium preparation have been proposed. In natural cycle FET (NC-FET), the endometrium develops under endogenous hormonal stimulation. The development of the dominant follicle and endometrium is monitored by ultrasound and FET is timed after triggering ovulation induction or determination of the spontaneous LH surge. In an artificial cycle FET (AC-FET) estrogens and progesterone are administered to prepare the endometrium for implantation. While the currently available data show no significant difference in pregnancy rates between these methods, well designed randomized controlled trials are lacking. Moreover there is little literature on difference in cancellation rates, cost-efficiency and adverse events. METHODS AND DESIGN: In this randomized, multi-centre, non-inferiority trial we aim to test the hypothesis that there is no significant difference in live birth rates between patients undergoing NC-FET versus AC-FET. The primary outcome will be live birth rate per embryo transfer procedure. Secondary outcomes will be ongoing and clinical pregnancy rate, cancellation rate, (serious) adverse events and cost-efficiency. Based on a live birth rate of 20% and a minimal clinical important difference of 7.5% (one-sided alpha 2.5%, beta 20%) a total of 1150 patients will be needed. Analyzes will be performed using both per protocol as well as intention to treat analyses. DISCUSSION: This prospective, randomized, non-inferiority trial aims to address the hypothesis that there is no significant difference in live birth rates between patients undergoing NC-FET versus patients undergoing AC-FET. Moreover it addresses cost-efficiency as well as the perceived burden of both treatments. TRIAL REGISTER: Netherlands trial register (NTR): 1586.

An economic evaluation of estrous synchronization and timed artificial insemination in suckled beef cows.

Partial budget analysis was used to determine the economic outcome of estrus synchronization (ES) and timed artificial insemination (TAI) in commercial cow-calf production. Suckled beef cows (n = 1,197) from 8 locations were assigned randomly within each location to 1 of 2 treatment groups: 1) cows were inseminated artificially after synchronization of ovulation using the CO-Synch + CIDR protocol, which includes a 100-µg injection of GnRH (OvaCyst; TevaAnimal Health, St. Joseph, MO) when a controlled internal drug-releasing device (CIDR; Pfizer Animal Health, New York, NY) containing 1.38 g of progesterone was inserted. The CIDR was removed 7 d later, and cows received a 25-mg injection of PGF(2α) (PGF; Lutalyse; Pfizer Animal Health), followed in 66 h with TAI and a second 100-µg injection of GnRH (TAI; n = 582), and 2) cows were exposed to natural service (NS) without estrous synchronization (Control; n = 615). Within each herd, cows from both treatments were maintained together in similar pastures and were exposed to bulls 12 h after the last cow in the TAI treatment was inseminated. Overall, the percentage of cows exposed to treatments that subsequently weaned a calf was greater (P < 0.05) for TAI (84%) than Control (78%) cows. In addition, survival analysis demonstrated that cumulative calving distribution differed (P < 0.05) between the TAI and Control treatments. Weaning weights per cow exposed to treatments were greater (P < 0.01) for cows in the TAI treatment (193.4 ± 4.3 kg) than those cows in the Control treatment (175.9 ± 4.3 kg). Overall, increased returns plus decreased costs ($82.32) minus decreased returns plus increased costs ($33.18) resulted in a $49.14 advantage per exposed cow in the TAI treatment compared with the Control treatment. Location greatly influenced weaned calf weights, which may have been a result of differing management, nutrition, genetic selection, production goals, and environments. We concluded that ES and TAI had a positive economic impact on subsequent weaning weights of exposed cows.

Steer responses to feeding soybean hulls and steroid hormone implantation on toxic tall fescue pasture.

Crossbred steers were grazed in the spring and early summer on endophyte-infected (Neotyphodium coenophialum), Kentucky-31 tall fescue (Lolium arundinaceum) pastures to evaluate effects and interactions of feeding pelleted soybean hulls (PSBH) and steroid hormone implants (SHI) on steer performance, serum prolactin, and hair coat ratings (HCR). Steers were stratified by BW for assignment to six 3.0-ha toxic tall fescue pastures. With or without daily PSBH feeding, treatments were assigned randomly to pastures as the main plot treatment in a split-plot design. Pelleted soybean hulls were group-fed to provide 2.3 kg(steer·d(-1)) (as fed). With or without SHI (200 mg of progesterone and 20 mg of estradiol) treatments were randomly assigned as the subplot treatment to 2 steer subgroups within each pasture. Sixty-four steers were grazed for 77 d in 2007, and 60 steers were grazed for 86 d in 2008. Pasture forage mass declined linearly over time, but the rate of decline was greater (P = 0.001) in 2007 than in 2008. Pasture forage mass was never below 2,300 kg of DM/ha in either year. Average daily gain for steers on the combined PSBH and SHI treatments was greater (P < 0.01) than for those on the PSBH-only, SHI-only, and control (no SHI, no PSBH) treatments. Average daily gain for the PSBH-only steers was greater (P < 0.01) than for SHI-only and control steers and tended (P = 0.063) to be greater for SHI-only than for control steers. Steroid implants did not affect (P = 0.826) serum prolactin concentrations; however, prolactin concentrations in PSBH steers, with or without SHI, were increased (P = 0.01) 2-fold over SHI-only and control steers. Feeding PSBH and SHI treatments both reduced (P < 0.05) the percentage of steers with rough HCR, and a greater percentage of steers fed PSBH tended (P < 0.076) to have sleek hair coats. An economic analysis was conducted, which determined that costs of additional ADG with PSBH feeding were below breakeven costs over a wide range of PSBH costs and cattle prices. Breakeven costs for PSBH-only treatment for a range of cattle prices of $1.80 to $2.40/kg of BW were less than $120/t, whereas with PSBH feeding combined with SHI the breakeven cost was less than $240/t. Results indicate that steers grazing endophyte-infected tall fescue can be fed PSBH and implanted with steroid hormones to cost effectively increase ADG and that feeding PSBH can increase serum prolactin concentrations and induce some shedding of rough hair coats.

Study of progesterone for the prevention of preterm birth in twins (STOPPIT): findings from a trial-based cost-effectiveness analysis.

OBJECTIVES: Preterm birth contributes to a range of healthcare problems amongst infants surmounting to sizeable healthcare costs. Twin pregnancies are at particular risk of preterm birth. The objective of this study was to assess the cost-effectiveness of vaginal progesterone gel for the prevention of preterm birth in twin pregnancies. METHODS: An economic evaluation was conducted alongside a randomized placebo controlled trial (the STOPPIT trial) of vaginal progesterone gel for the prevention of preterm birth in twin pregnancies. Five hundred women were recruited from nine maternity hospitals in the United Kingdom. The outcomes of the economic evaluation were presented in terms of net benefit statistics, cost-effectiveness acceptability curves, generated using the nonparametric bootstrap method, and the expected value of perfect information. RESULTS: Mean health service costs between the period of randomization and discharge for mother and infant were 28,031 pound sterling in the progesterone group and 25,972 pound sterling in the placebo group, generating a mean nonsignificant cost difference of 2,059 pound sterling (bootstrap mean cost difference 2,334 pound sterling; 95 percent confidence interval: -5,023 pound sterling, 9,142 pound sterling; p = .33). The probability of progesterone being cost-effective was 20 percent at a willingness to pay threshold of 30,000 pound sterling per preterm birth prevented. There is little economic justification for conducting further research into the use of vaginal progesterone gel in twin pregnancies for the prevention of preterm birth. CONCLUSIONS: Further studies of preventive interventions for preterm birth more generally are required given the scale of the clinical and economic burden of this condition. These studies should be sufficiently powered for economic endpoints and extend beyond hospital discharge.

Economic comparison of timed artificial insemination and exogenous progesterone as treatments for ovarian cysts.

The objective of this study was to compare the economic benefits of timed artificial insemination (AI) and a progesterone insert as therapeutic treatments for cows diagnosed with cystic ovarian disease (COD). A secondary objective was to illustrate the use of a stochastic dynamic simulation model to fully account for all changes in revenues and costs affected by differences in treatments. First, 4 herds of 1,000 cows each were simulated until steady state. These cows were free from COD and inseminated based on estrus only. Herds differed by probability of estrus detection (46 or 70%) and days in milk (DIM) when nonpregnant cows were culled (330 or 400 d). Second, 3 herds were created with 1,000 nonpregnant cows at 90, 170, or 250 DIM. These cows were considered diagnosed with COD at the start of the simulation (d 0); no new cases of COD developed after d 0. Cows spontaneously recovered or were treated. Treatments were either timed AI or intravaginal device containing progesterone followed by PGF(2alpha) and then AI if estrus was detected. Effects of treatments were evaluated in 48 scenarios based on compliance of timed AI (82 or 100%), probability of estrus detection (46 or 70%), and DIM when nonpregnant cows were culled (330 or 400 d). As cows became pregnant or were replaced, the herd evolved into the associated steady-state herd. Seven scenarios resulted in less than 50% of cows conceiving before they were culled. The percentage of cows diagnosed with COD that calved again ranged from 14.0 to 74.4% and was significantly reduced when COD was diagnosed later in lactation. Treatments in all cases were more valuable than waiting for spontaneous recovery. The average values of timed AI (82 or 100% compliance) and the progesterone insert were 83.29 dollars, 86.83 dollars, and 71.89 dollars, respectively, compared with waiting for spontaneous recovery. Treatments were least beneficial at 90 DIM. The benefits of timed AI (82 or 100% compliance) compared with the progesterone insert, adjusted for DIM and days to culling, were 14.98 dollars and 21.53 dollars when the probability of estrus detection was 46%. At 70% probability of estrus detection, the benefits were 7.81 dollars and 8.34 dollars, respectively. Overall benefit of treatment by timed AI was 11.39 dollars greater than by progesterone insert.

Hormone replacement therapy: current concerns and considerations.

AUDIENCE: This activity is designed for pharmacists and other healthcare professionals who evaluate and treat perimenopausal and postmenopausal women. GOALS: To understand the benefits, risks, and adverse effects associated with estrogen replacement therapy (ERT) and hormone replacement therapy (HRT) and their influence on a postmenopausal woman's initiation, adherence, and satisfaction with therapy. OBJECTIVES: 1. Discuss menopause and its effects. 2. Identify ERT/HRT's potential benefits and risks. 3. Discuss ERT/HRT's adverse effects and management approaches. 4. Identify various administration routes for ERT/H RT. 5. Identify currently available ERT/HRT products. 6. Recognize potential reasons for lack of initiation and continuation as well as ways to improve adherence in patients.

Quality of life and costs associated with micronized progesterone and medroxyprogesterone acetate in hormone replacement therapy for nonhysterectomized, postmenopausal women.

BACKGROUND: Because natural progesterone is poorly absorbed and rapidly metabolized, synthetic derivatives of progesterone, such as medroxyprogesterone acetate (MPA), are used in combination with estrogen in hormone replacement therapy. A micronized form of natural progesterone is available that is readily absorbed and reaches peak serum concentrations from 1 to 4 hours after administration. OBJECTIVE: The purpose of this study was to compare the quality of life (QOL), menopausal symptoms, and costs associated with a natural micronized progesterone (MP) formulation versus MPA as add-on therapy to estrogen in hormone replacement for post-menopausal women. METHODS: This prospective, multicenter, randomized, fixed-dose, open-label, parallel-group study enrolled postmenopausal, otherwise healthy, nonhysterectomized women 45 to 65 years of age who had been amenorrheic for > or =6 months and exhibited symptoms of estrogen deficiency. All women received 0.625 mg conjugated equine estrogens on days 1 to 25 of a 30-day cycle; on days 12 to 25, women were randomized to receive either MP 200 mg or MPA 5 mg; patients were followed for 9 months. QOL, the primary end point, was measured at baseline and months 3, 6, and 9 using the 36-Item Short-Form Health Survey (SF-36), the Nottingham Health Profile (NHP), and the condition-specific Women's Health Questionnaire (WHQ). Bleeding pattern, compliance, menopausal symptoms, and cost were evaluated as secondary end points. Costs (in 1997 Canadian dollars) were assessed from the societal perspective and included costs of study medication, hormone therapy monitoring, concomitant medication, outpatient resources, out-of-pocket expenses, and patient and caregiver time loss. RESULTS: A total of 182 women were enrolled; 89 received MP and 93 received MPA. Improvements in climacteric symptoms were observed from baseline to month 9 for both treatments. Mean scores on all domains of the SF-36 at month 9 were greater than scores at baseline in both treatment groups but the increases were not statistically significant. All domains within the NHP and WHQ improved significantly over this period for both groups (P < or = 0.008). Only patients receiving MP showed specific improvements in the menstrual problems and cognitive domains of the WHQ. The difference in average 9-month cost per patient was not statistically significant, at Can 367 dollars +/- 120 dollars and Can 360 dollars +/- 369 dollars for patients receiving MP and MPA, respectively. CONCLUSIONS: MP is a clinically effective, well-tolerated, and cost-comparable alternative to MPA.