This was an observational cohort study of female patients age 18-89 treated for menopause-related hormone imbalances from January 1, 2003 to April 30, 2010 in six community pharmacies. The University of Texas Health Science Center at San Antonio Institutional Review Board reviewed and approved this study; protocol number HSC20090507H. Oakdell Pharmacy, Inc. is comprised of six independent community pharmacies located throughout San Antonio, Texas and has offered BHRT consultation services since 2003. Currently, more than 1,000 women receive their compounded BHRT at Oakdell Pharmacy. Patient charts are maintained locally at the pharmacy.
Pharmacists who provide BHRT consultation services at Oakdell Pharmacy are trained through PCCA educational symposiums and other BHRT-focused seminars. At these seminars, credentialed medical professionals (e.g., physicians and pharmacists) provide evidence-based BHRT education. In addition, pharmacists who care for BHRT patients at Oakdell must have BHRT-related continuing education credit.
Patients are referred to the Oakdell Wellness Center through physicians, family members, and friends. BHRT consultation services consist of an extensive initial evaluation, hormone replacement education, and follow-up visits. Patients complete a new patient evaluation form and a laboratory hormone panel prior to their initial visit. This hormone panel, determined through serum or salivary testing, aids in identification of sex hormone deficiencies, adrenal function deficiencies, and thyroid dysfunction. Additional hormone panels are recommended 3-6 months after BHRT initiation, annually, and when deemed necessary to assist with BHRT customization. During the initial evaluation, patients are questioned regarding medical history, menopausal symptoms, and treatment goals. They are educated on several components of hormone therapy including: hormonal changes of menopause, causative factors associated with menopausal symptoms, risks and benefits of hormone therapy (both conventional and bioidentical therapies), and different BHRT dosage forms. During initial evaluation and follow-up visits, pharmacists use a standardized form to monitor symptom resolution and adverse effects. This form lists several symptoms associated with menopause. Patients are asked to indicate whether their symptoms are "absent," "mild," "moderate," or "severe."
The pharmacist and patient decide on an individualized treatment plan consisting of either (1) a prescription recommendation to be faxed to their physician for modification, signature, and approval and/or (2) over-the-counter (OTC) products. The pharmacist's letter to the physician describes the patient's hormone imbalance(s), laboratory results, and current menopausal symptoms. It also suggests a customized BHRT regimen and outlines the benefits of compounded BHRT. BHRT compounds vary by active ingredients, dose, and dosage form. Once the physician's approval is received, the individualized BHRT compound is prepared. The most common compounded BHRT hormones include: biest (estriol/estradiol in varying concentrations), triest (estriol/estradiol/estrone), progesterone, testosterone, and dehydroepiandosterone (DHEA). Table depicts common bioidentical hormone dose classifications.
Common Compounded Bioidentical Hormones Dose Classifications
Patients are instructed to complete monthly evaluation forms for the first few months and every six months thereafter to monitor menopausal symptoms and side effects. Upon review of a patient's evaluation form, the pharmacist decides if further laboratory work, telephone, or face-to-face follow-up is needed. The pharmacist then makes changes to the patient's therapy in consultation with the patient and their physician.
Women ≥18 years of age receiving compounded BHRT at Oakdell Pharmacy Inc., from January 1, 2003 to April 30, 2010 were eligible for this study. Patients were excluded if they received compounded BHRT from Oakdell Pharmacy, but were managed outside the Oakdell Pharmacy system (i.e., physicians' offices). Patients were also excluded if they did not complete a follow-up hormone evaluation form. All data were collected at Oakdell Pharmacy from the existing medical records.
A customized, data collection instrument was developed using Microsoft Access 2007®
software. The instrument was designed to mimic the appearance of the initial patient intake and follow-up forms used during pharmacist consultations at Oakdell Pharmacy. All research personnel were trained on the tool prior to collection of any patient data. Data included patient demographics, comorbidities, laboratory values, medications, and adverse effects of hormone therapy. The last-observation-carried-forward (LOCF) method was used to determine BHRT effectiveness at 3 and 6 months follow-up. If patient data were available at 6 months, those data were used. That is, if patient data were available at 3 months, but not 6 months, then the data from 3 months were used. LOCF is an accepted method used by other HRT studies [5
The dependent variables utilized in this study were vasomotor symptoms, mood symptoms, myocardial infarction, and breast cancer. A decrease in symptom intensity was defined as a decrease in symptom ratings from baseline to follow-up (three to six months). Baseline and follow-up symptom ratings were also compared at each time point using the percentage of patients reporting either "moderate" or "severe." Reduction in symptom severity was also evaluated in a subgroup analysis of women between the ages of 40 and 70 years.
Myocardial infarction and breast cancer adverse event rates were reported as events and cases per 10,000 person years. Adverse event (AE) rates were calculated with the following method: number of AE/[(average time to AE) X (# of patients with AE follow-ups). This number was then multiplied by 10,000 to give AE rates per 10,000 person years.
The independent variables utilized in this study were BHRT regimen and BHRT dosage form. The term "estrogen" was used to describe the use of any of the estrogen combinations [i.e., triest (estriol 80%/estradiol 10%/estrone 10%), biest (estriol 80%/estradiol 20%), biest (estriol 70%/estradiol 30%), and biest (estriol 50%/estradiol 50%)].
Patient's length of therapy (LOT) was obtained from the pharmacy records and patient charts. LOT was calculated using the following method: date of most current BHRT prescription fill minus date of original fill. The patient's treatment timeframe was obtained from pharmacy records and was calculated as the date of follow-up minus the date of baseline assessment.
Data and Statistical Analysis
All statistical analyses were performed using JMP 8.0® (SAS Corp., Cary, NC). Statistical significance was defined as an alpha less than 0.05. Descriptive statistics (e.g., means, medians, and frequencies) were used to characterize the patient demographics, BHRT use, symptom resolution, and adverse effects. Patient demographics, baseline characteristics, comorbid conditions, baseline menopausal symptoms, dosing regimens, symptom improvement, and adverse effects were compared between groups. Categorical variables were compared using chi-square and Fisher's exact tests. Continuous variables were tested for normality using the Shapiro Wilk-W Test. Normally distributed variables were reported as means (standard deviations), while non-normally distributed variables were reported as medians (25th and 75th percentiles). Paired data were compared using the Wilcoxon signed-rank test. All tests were two-sided.