James P. Symons

Histologic classification and pathologic findings for endometrial biopsy specimens obtained from 2964 perimenopausal and postmenopausal women undergoing screening for continuous hormones as replacement therapy (CHART 2 Study)

OBJECTIVE The aim of this study was to screen for disorders and to histologically classify endometrial biopsy specimens from 2964 perimenopausal and postmenopausal women who were candidates for hormonal replacement therapy. STUDY DESIGN Endometrial biopsy specimens were obtained with a Vabra aspiration curette, processed by standard methods, and stained by hematoxylin and eosin and special methods to reveal subtle features of the endometrium. RESULTS Of the endometrial biopsy specimens, 68.7% were atrophic, 23.5% were proliferative, 0.5% were secretory, 0.6% were hyperplastic, 0.07% were adenocarcinoma, and 6.6% were insufficient for classification. Three independent senior microscopists agreed on the classification of each biopsy specimen. CONCLUSION The number of patients is the largest ever screened for a single hormone replacement therapy study. The low yield of endometrial cancer indicates that biopsies are unnecessary before hormone replacement therapy is initiated in asymptomatic women.

Unscheduled bleeding during initiation of continuous combined hormone replacement therapy: A direct comparison of two combinations of norethindrone acetate and ethinyl estradiol to medroxyprogesterone acetate and conjugated equine estrogens

ObjectiveTo determine whether there are differences between continuous combined hormone replacement therapies on bleeding control. DesignNine hundred and forty-five postmenopausal women were randomized to one of seven double-blind treatment groups (placebo, 0.25 mg norethindrone acetate (NA)/5 &mgr;g ethinyl estradiol (EE), 1 mg NA/5 &mgr;g EE, 0.5 mg NA/10 &mgr;g EE, 1 mg NA/10 &mgr;g EE, 5 &mgr;g EE, and 10 &mgr; EE) or unmasked 0.625 mg conjugated equine estrogens (CEE)/2.5 mg medroxyprogesterone acetate (MPA). Treatment was for 12 months; subjects kept daily diaries recording whether they had bleeding and/or spotting. ResultsThe results focused on currently commercially available hormone replacement therapy products (femhrt [1 mg NA/5 &mgr;g EE] and Prempro [0.625 mg CEE/2.5 mg MPA]) as well as a high-dose NA/EE dose combination (1/10) over the first 6 months of use, the most critical period in establishing treatment adherence. At the end of month 6 there was a greater incidence of amenorrhea with both NA/EE dose combinations compared with CEE/MPA (p = 0.009 for 1 mg NA/5 &mgr;g EE and p = 0.006 for 1 mg NA/10 &mgr;g EE). Statistically significantly more women were amenorrheic at every month based on cumulative amenorrhea for 1 mg NA/5 &mgr;g (p < 0.05) compared with CEE/MPA; at months 3 and 6 more women were amenorrheic on 1 mg NA/10 &mgr;g EE compared with CEE/MPA using the cumulative amenorrhea parameter. ConclusionsThe results indicate that statistically significantly more women attained amenorrhea based on various parameters when administered continuous combined NA/EE compared with CEE/MPA. The potential for long-term treatment compliance based on better bleeding control may optimize the opportunity to prevent osteoporosis as well as other associated health benefits.

A Methodology Study to Validate a Structured Diagnostic Method Used to Diagnose Female Sexual Dysfunction and Its Subtypes in Postmenopausal Women

The currently accepted gold standard for diagnosis of female sexual dysfunction (FSD) is a nonstandardized interview by a clinician whose field of expertise is FSD. However, the limited number of experts in the field has implications for running efficient large-scale clinical trials. Therefore, we developed a structured diagnostic method (SDM) to enable diagnosis of FSD in postmenopausal women by health care professionals who are not FSD experts. Our study objectives were to evaluate both convergent validity and intrarater reliability of the SDM. The results showed that the method had good convergent validity and excellent intrarater reliability. Thus, we conclude that the SDM can reliably diagnose FSD status and FSD subtypes in postmenopausal women.