Continuation of postmenopausal hormone replacement therapy: comparison of cyclic versus continuous combined schedules.

Discontinuation of hormone replacement therapy (HRT) is much more common than what is reported in randomized, double-blind clinical trials. Our purpose in this retrospective study, using a prescription database, was to compare the continuation rate among women who took cyclic combination therapy adding progesterone to estrogen (CYC-PERT) or continuous combined estrogen progestin therapy (CC-PERT). The study subjects were 1,532 women, ≥45 years old, who initially filled index prescriptions for 0.625 mg conjugated estrogens. They were divided into two groups (CYC-PERT = 644, CC-PERT = 888) on the basis of coprescribed medroxyprogesterone. We found that for all women initiating therapy, 35-40% did not return for a refill and 76-81% stopped therapy within 3 years. Those prescribed CC-PERT initially were more likely to stop than those prescribed CYC-PERT (rate ratio [RR] = 1.20; 95% confidence interval [CI] = 1.06-1.35). Adjustments for age, year of starting medication, cost of medication, and prescriber specialty did not affect the difference in discontinuation between the two regimens (RR 1.18, 95% CI = 1.04-1.34). We conclude that the likelihood of women continuing HRT beyond 3 years of initiation is low. Furthermore, compared with CYC-PERT users, those receiving CC-PERT have a slightly higher probability of discontinuation. Efforts should be made to understand why three quarters of women beginning HRT will stop it long before it can provide major long-term benefit.

Bazedoxifene for HRT?

Duavive (Pfizer) is a modified-release formulation of conjugated oestrogens plus bazedoxifene acetate (a selective oestrogen receptor modulator). It is licensed for treatment of oestrogen deficiency symptoms in postmenopausal women with a uterus for whom treatment with progestogen-containing therapy is not appropriate.1,2 It was licensed by the European Medicines Agency (EMA) in 2014 and launched in the UK in July 2016.1,3 Here, we review the evidence on efficacy and safety of conjugated oestrogens/bazedoxifene and consider its place in the management of symptoms associated with the menopause.

Economic impact of Tibolone compared with Continuous-Combined Hormone Replacement Therapy in the management of climacteric symptoms in postmenopausal women.

BACKGROUND: Deciding whether to treat postmenopausal women suffering from climacteric symptoms with Continuous Combined Hormone Replacement Therapy (CCHRT) has become increasingly difficult after the release of the Women's Health Initiative results. As a result, development of alternatives to CCHRT is required. Tibolone, which is a synthetic steroid that has estrogenic, progestogenic and androgenic properties, is reported to be a promising alternative. It has been used in Europe, in the same indication as CCHRT, for approximately 20 years but is not yet available in Canada. OBJECTIVE: We carried out a cost-utility analysis comparing a 3-year-treatment course with Tibolone 2.5mg and conjugated equine estrogens (CEE)/medroxyprogesterone acetate (MPA) (0.625 mg/2.5 mg) in the management of postmenopausal women with climacteric symptoms. METHODS: A Markov model, considering persistence, vaginal bleeding and climacteric symptoms, was elaborated to compare the different options in terms of cost and Quality Adjusted Life Years (QALYs), according to a public third-party payer perspective. RESULTS: Compared with CEE/MPA, Tibolone led to an increase in cost (dollars 485 for Tibolone versus dollars 232 for CEE/MPA) and a slight increase in QALYs (2.08 for Tibolone versus 2.05 for CEE/MPA). Consequently, the incremental cost per QALY gained ratio was dollars 9198. CONCLUSION: According to the results, Tibolone seems to be a cost-effective alternative to CEE/MPA. However, those results should be interpreted with caution insofar as the difference in terms of QALY is clinically difficult to value and taking into account the limited data on Tibolone's long-term innocuity.

[Equine estrogens vs. esterified estrogens in the climacteric and menopause. The controversy arrives in Mexico]. / Estrógenos equinos vs. estrógenos esterificados en el climaterio y la menopausia. La controversia llega a México.

It exists controversies about if the effects and benefits of the esterified estrogens could be similar to those informed for equines, because its chemical composition and bioavailability are different. Esterified estrogens has not delta 8,9 dehydroestrone, and its absorption and level of maximum plasmatic concentrations are reached very fast. In United States of America and another countries, esterified estrogens has been marketed and using for treatment of climacteric syndrome and prevention of postmenopausal osteoporosis, based on the pharmacopoiea of that country, but the Food and Drug administration (FDA) has not yet authorized up today, a generic version of conjugated estrogens. In Instituto Mexicano del Seguro Social (IMSS) and another institutions of health sector in Mexico, starting in year 2000, it has been used esterified estrogens for medical treatment of climacteric and menopausal conditions. For this reason, in this paper we revised the most recent information about pharmacology, chemical composition, clinical use and costs of the conjugated estrogens with the purpose to guide the decisions to purchase this kind of drugs in Mexican heath institutions.

Evaluation of a formulary switch from conjugated to esterified estrogens in a managed care setting.

BACKGROUND: Formulary switches between agents in the same therapeutic class have become commonplace in the managed care setting as a strategy to reduce costs. OBJECTIVES: We evaluated the impact of a formulary switch from conjugated to esterified estrogen tablets at the Fallon Community Health Plan, a mixed-model health maintenance organization. DESIGN: A retrospective study was conducted with the use of the automated database of the health plan. SUBJECTS: Study subjects were members of the health plan during the period from May 1, 1995, to December 31, 1997, who were dispensed > or =1 estrogen replacement product. From this population, a cohort of users of conjugated estrogens during the period from May 1, 1995, to October 31, 1995, was selected. MEASURES: The cumulative incidence of switching from conjugated to esterified estrogen tablets and subsequent discontinuations of esterified estrogens was evaluated. The frequencies of ambulatory encounters during the 6 months before and after a switch or discontinuation were compared. RESULTS: During the period after promotion of the formulary switch, 2,149 of 2,984 patients (72%) originally dispensed conjugated estrogen tablets switched to esterified estrogen tablets. Among those patients switching to esterified estrogens, an excess of 20 office visits per 100 patients was noted in the postswitch period (P = 0.005). The risk of switching back to conjugated estrogen tablets was 15% by 2 years. CONCLUSIONS: The findings of this study suggest that plan efforts were successful in switching most users of conjugated estrogens to esterified estrogens. The switch was associated with an increase in utilization of health care services.

Acceptability of a substitution of estrogen replacement therapy to women enrolled in a health maintenance organization.

We evaluated the acceptability of a systematic estrogen replacement therapy (ERT) substitution program in a large U.S. health maintenance organization (HMO). Prescriptions for 14,601 enrollees were converted from Premarin tablets (PR) to Estratab tablets (ES). At the end of 6 months, 93.5% of the women continued to use ES, and 6.5% reverted to use of PR. We report the results of a telephone survey that included women randomly selected from three groups who participated in the substitution program. The groups were women whose prescriptions were converted from PR to ES (n = 253), women whose prescriptions were converted from PR to ES and back to PR (n = 250), and women who continued to use PR without converting to ES (n = 251). Two thirds of women who did not revert to use of PR were still using ES 3 years after conversion of their prescriptions. Women whose prescriptions were converted but who returned to use of PR cited both return of menopausal symptoms and development of new symptoms as reasons. Women who continued to use ES did not report return of menopausal symptoms after the conversion. Our evidence supports the conclusion that the substitution of Estratab tablets for Premarin tablets among users of ERT was well tolerated and acceptable to most affected women in this HMO setting.

Correcting prolonged bleeding during renal transplantation with estrogen or plasma.

OBJECTIVE: To determine the efficacy and relative effectiveness of conjugated entrogens (CE) and fresh-frozen plasma (FFP) in normalizing prolonged preoperative bleeding times during renal transplantation. DESIGN: Prospective, randomized trial. SETTING: A university regional referral center for transplantation. PATIENTS: Patients scheduled for renal transplantation with preoperative bleeding times greater than 10 minutes (normal, < 7 minutes) following informed consent were asked to participate in the randomized protocol. Those with bleeding times of 8 to 9.5 minutes were asked, following informed consent, to be a control group receiving neither CE nor FFP. INTERVENTIONS: Following induction of anesthesia and drawing of baseline laboratory tests, patients were administered randomly, using a table of random numbers, either 50 mg of CE or 2 U of FFP. MAIN OUTCOME MEASURES: Bleeding time measurements and other laboratory tests were repeated at the end of surgery as well as at 24 and 48 hours postoperatively. RESULTS: Treatment with CE and FFP decreased the patients' bleeding times from 16.68 +/- 0.8 (SEM) and 17.13 +/- 0.85 minutes to 7.67 +/- 0.79 (P < .001) and 10.50 +/- 1.27 minutes (P < .001), respectively, by the end of surgery. At 24 and 48 hours postoperatively, the CE group had bleeding times of 9.77 +/- 0.99 and 9.81 +/- 1.24 minutes (P < .001 for both), respectively, whereas the FFP group bleeding times were 12.76 +/- 1.57 (P = .003) and 12.14 +/- 1.56 minutes (P = .001), respectively. There were no statistical differences for the control group compared with baseline either at the end of surgery or at 24 hours. CONCLUSIONS: Although both CE and FFP significantly decreased prolonged preoperative bleeding times during renal transplantation, CE might be preferred because of lower risk and cost, as well as a longer duration of action.