Effect of hormone replacement and selective estrogen receptor modulators (SERMs) on the biomechanics and biochemistry of pelvic support ligaments in the cynomolgus monkey (Macaca fascicularis).

OBJECTIVE: To evaluate the effect of selective estrogen receptor modulators and ethinyl estradiol on the biomechanical and biochemical properties of the uterosacral and round ligaments in the monkey model of menopause. STUDY DESIGN: A randomized, double-blind, placebo-controlled study on 11 female macaque monkeys. Ovariectomized monkeys received 12 weeks of placebo, raloxifene, tamoxifen, or ethinyl estradiol. Biomechanical step-strain testing and real-time polymerase chain reaction was performed on the uterosacral and round ligaments. RESULTS: Tamoxifen and raloxifene uterosacrals expressed differing collagen I/III receptor density ratios, but both selective estrogen receptor modulators showed decreased tensile stiffness compared to ethinyl estradiol and controls. CONCLUSION: These findings support a possible effect of selective estrogen receptor modulators on biomechanical and biochemical properties of uterosacrals. This may play a role in pelvic organ prolapse.

Validation of a simplified technique for using the POPQ pelvic organ prolapse classification system.

Our objective was to determine the inter-examiner agreement of a simplified pelvic organ prolapse quantification (POPQ) exam and to assess its correlation with the standard POPQ exam. This study consists of two parts; both were performed in a prospective, randomized, blinded fashion on women presenting with complaints attributed to pelvic organ support defects. The first study was done to determine the inter-examiner reliability of a simplified POPQ exam. The simplified POPQ exam is based on the POPQ with similar ordinal staging but with only four points measured instead of nine. Forty-eight women underwent exams by five different investigators. The order of exams was randomized and the examiners were blinded to the results of each other's findings. The results of these two exams were compared using weighted kappa statistics. The second part of the study was done to determine the inter-system agreement between the simplified vs standard POPQ exam. A group of 49 women were examined by four different investigators: one using the simplified and the other using standard POPQ exams. The order of the exams was randomized and the examiners were blinded to the results of each other's exam. Kendall's tau-b statistics were used to determine the inter-system agreement. For the inter-examiner reliability of the POPQ exam, the average age was 60+/-13 years. The weighted kappa statistics for the inter-examiner reliability of the simplified prolapse classification system were 0.86 for the overall stage, 0.89 and 0.86 for the anterior and posterior vaginal walls, respectively, 0.82 for the apex/cuff, and 0.72 for the cervix. All demonstrate significant agreement. For the inter-system association between the simplified POPQ and standard POPQ, the average age was 61+/-15 year. The Kendall's tau-b value for overall stage was 0.90, 0.83, and 0.87 for the anterior and posterior walls respectively, and 0.78 for the cuff/apex and 0.98 for the cervix. There is good inter-examiner agreement of a simplified POPQ classification system and it appears to have good inter-system association with the POPQ.

The effects of hormone replacement on the biomechanical properties of the uterosacral and round ligaments in the monkey model.

OBJECTIVE: The purpose of this study was to determine effects of ovariectomy (OVX) and conjugated equine estrogens plus medroxyprogesterone acetate (CEE/MPA), or ethinyl estradiol plus norethindrone acetate (EE/NA) on biomechanics of uterosacral (USL) and round (RL) ligaments in postmenopausal (PMP) monkeys. STUDY DESIGN: This was a randomized, triple blind, placebo-controlled study. OVX monkeys received 12 months no treatment (Pbo) (n = 19), CEE/MPA (n = 19), or EE/NA (n = 21). USL and RL step strains and stress-relaxation data were curve-fitted, giving strain-dependent tensile modulus (TM) from 0% to 30%. RESULTS: (1) USL: TM for both treatment groups was greater than Pbo for strains from 0% to 12% (P < .04). (2) RL: TM for both treatment groups was smaller than Pbo for strains from 12% to 30% (P < .05). No differences were found between treatment regimens. CONCLUSION: CEE/MPA and EE/NA both affect functional biomechanical properties by increasing tensile stiffness in the USL and decreasing it in the RL.

Pessary reduction and postoperative cure of retention in women with anterior vaginal wall prolapse.

This study aimed to determine whether preoperative pessary reduction of anterior vaginal wall prolapse in patients with elevated postvoid residual (PVR) volumes relieves urinary retention, and if reconstructive pelvic surgery in these patients cures urinary retention. The records of all women with symptomatic anterior vaginal wall and urinary retention (PVR >or=100 cc) who underwent evaluation and surgical repair of the anterior vaginal wall at our institution between 1996 and 1999 were retrospectively reviewed. All patients underwent a detailed urogynecologic and urodynamic evaluation and had a pessary trial prior to surgery. Cure of urinary retention was defined as PVR <100 cc at 3 months postoperatively. Sensitivity, specificity, positive and negative predictive values for pessary reduction testing were calculated. Twenty-four patients met the inclusion criteria. Two patients (8%) had stage 2, eleven (46%) stage 3, and eleven (46%) stage 4 anterior vaginal wall prolapse. Preoperatively, the use of pessary was associated with relief of urinary retention in 75% patients. In predicting postoperative cure of urinary retention, pessary testing had a sensitivity of 89%, specificity of 80%, positive predictive value of 94%, and negative predictive value of 67%. Nineteen of 24 patients had a PVR <100 cc postoperatively, indicating a 79% cure rate for urinary retention. In women with symptomatic anterior vaginal wall prolapse and urinary retention, use of a pessary is associated with relief of retention in the majority of patients. Furthermore, pessary reduction testing has good sensitivity, specificity, and positive predictive value for postoperative voiding function.

Short-term urogenital effects of raloxifene, tamoxifen, and estrogen.

OBJECTIVE: The purpose of this study was to assess the urogenital effects of raloxifene, tamoxifen, conjugated equine estrogen, and placebo in healthy postmenopausal women. STUDY DESIGN: This randomized, double-blind, placebo-controlled study compared the urogenital effects of 0.625 mg of conjugated equine estrogen (n = 15 women), 20 mg of tamoxifen (n = 14 women), 60 mg of raloxifene, (n = 15 women), and placebo (n = 13 women). Evaluations at baseline and evaluations after 20 weeks receiving the drug included a pelvic examination with cytologic evaluation of vagina and urethra, pelvic organ prolapse quantitation, and urethral axis deflection by cotton swab test (only in patients with incontinence [33%]). RESULTS: Conjugated equine estrogen increased the maturation value of both urethral and vaginal cytologic condition (P =.002, P =.032, respectively). There was a decrease in vaginal maturation value in the raloxifene group (not significant). Two of 8 women in the conjugated equine estrogen group showed evidence of worsening prolapse by pelvic organ prolapse quantitation; the condition of 2 of 8 women improved. In the raloxifene, tamoxifen, and placebo groups 8 of 12 women, 4 of 13 women, and 2 of 11 women had worsening in prolapse scores, respectively, whereas none of the women had improvement. Increased cotton swab deflection was found in 3 of 5 women in the raloxifene group, in 5 of 8 women in the tamoxifen group, in 0 of 4 women in the placebo group, and in 0 of 2 women in the conjugated equine estrogen group. Seventy-five percent of the patients who received raloxifene and 60% of the patients who received tamoxifen had increases in prolapse by any measure (ie, pelvic organ prolapse quantitation or cotton swab or clinical assessment) compared with 18% of the patients in the placebo group and 22% of the patients in the conjugated equine estrogen group (P =.015), although symptoms did not differ among groups. CONCLUSION: Neither raloxifene nor tamoxifen improve cytohormonal effects in the vagina or urethra, whereas conjugated equine estrogen does. Raloxifene and tamoxifen appear to show worsening prolapse compared with conjugated equine estrogen and placebo. The clinical relevance of these effects is unknown and requires investigation.