Perioperative Vaginal Estrogen as Adjunct to Native Tissue Vaginal Apical Prolapse Repair: A Randomized Clinical Trial.

Importance: Surgical repairs of apical/uterovaginal prolapse are commonly performed using native tissue pelvic ligaments as the point of attachment for the vaginal cuff after a hysterectomy. Clinicians may recommend vaginal estrogen in an effort to reduce prolapse recurrence, but the effects of intravaginal estrogen on surgical prolapse management are uncertain. Objective: To compare the efficacy of perioperative vaginal estrogen vs placebo cream on prolapse recurrence following native tissue surgical prolapse repair. Design, Setting, and Participants: This randomized superiority clinical trial was conducted at 3 tertiary US clinical sites (Texas, Alabama, Rhode Island). Postmenopausal women (N = 206) with bothersome anterior and apical vaginal prolapse interested in surgical repair were enrolled in urogynecology clinics between December 2016 and February 2020. Interventions: The intervention was 1 g of conjugated estrogen cream (0.625 mg/g) or placebo, inserted vaginally nightly for 2 weeks and then twice weekly to complete at least 5 weeks of application preoperatively; this continued twice weekly for 12 months postoperatively. Participants underwent a vaginal hysterectomy (if uterus present) and standardized apical fixation (either uterosacral or sacrospinous ligament fixation). Main Outcomes and Measures: The primary outcome was time to failure of prolapse repair by 12 months after surgery defined by at least 1 of the following 3 outcomes: anatomical/objective prolapse of the anterior or posterior walls beyond the hymen or the apex descending more than one-third of the vaginal length, subjective vaginal bulge symptoms, or repeated prolapse treatment. Secondary outcomes included measures of urinary and sexual function, symptoms and signs of urogenital atrophy, and adverse events. Results: Of 206 postmenopausal women, 199 were randomized and 186 underwent surgery. The mean (SD) age of participants was 65 (6.7) years. The primary outcome was not significantly different for women receiving vaginal estrogen vs placebo through 12 months: 12-month failure incidence of 19% (n = 20) for vaginal estrogen vs 9% (n = 10) for placebo (adjusted hazard ratio, 1.97 [95% CI, 0.92-4.22]), with the anatomic recurrence component being most common, rather than vaginal bulge symptoms or prolapse repeated treatment. Masked surgeon assessment of vaginal tissue quality and estrogenization was significantly better in the vaginal estrogen group at the time of the operation. In the subset of participants with at least moderately bothersome vaginal atrophy symptoms at baseline (n = 109), the vaginal atrophy score for most bothersome symptom was significantly better at 12 months with vaginal estrogen. Conclusions and Relevance: Adjunctive perioperative vaginal estrogen application did not improve surgical success rates after native tissue transvaginal prolapse repair. Trial Registration: ClinicalTrials.gov Identifier: NCT02431897.

Protease Inhibition Improves Healing of The Vaginal Wall after Obstetrical Injury: Results from a Preclinical Animal Model.

Vaginal delivery with obstetrical trauma is a risk factor for pelvic organ prolapse later in life. Loss of fibulin-5 (FBLN5), an elastogenesis-promoting cellular matrix protein, results in prolapse in mice. Here, we evaluated effects of pregnancy, parturition, and obstetrical injury on FBLN5 content, elastic fibers, biomechanics, and histomorphology of the vaginal wall in rats. Further, we analyzed the effects of actinonin, a protease inhibitor, on obstetrical injury of the vaginal wall. Vaginal FBLN5 decreased significantly in pregnancy, and injury resulted in further downregulation. Stiffness of the vaginal wall decreased 82% in pregnant rats and 74% (p = 0.019) with injury relative to uninjured vaginal delivery controls at 3d. Actinonin ameliorated loss of FBLN5, rescued injury-induced loss of elastic fibers and biomechanical properties after parturition, and reduced the area of injury 10-fold. We conclude that pregnancy and parturition have a profound impact on vaginal FBLN5 and biomechanics of the vaginal wall. Further, obstetrical injury has significant deleterious impact on recovery of the vaginal wall from pregnancy. Actinonin, a non-specific matrix metalloprotease inhibitor, improved recovery of the parturient vaginal wall after obstetrical injury.

Effects of preoperative local estrogen in postmenopausal women with prolapse: a randomized trial.

CONTEXT: Pelvic organ prolapse (POP) increases in prevalence with age; recurrence after surgical repair is common. OBJECTIVE: The objective of the study was to determine the effects of local estrogen treatment on connective tissue synthesis and breakdown in the vaginal wall of postmenopausal women planning surgical repair of POP. DESIGN: This was a randomized trial. SETTING: The study was conducted at an academic tertiary medical center. PATIENTS OR OTHER PARTICIPANTS: Postmenopausal women with a uterus and symptomatic anterior and/or apical prolapse at stage 2 or greater participated in the study. INTERVENTION: Estrogen (Premarin) or placebo cream for 6 weeks preoperatively was the intervention. MAIN OUTCOME MEASURES: Full-thickness anterior apical vaginal wall biopsies were obtained at the time of hysterectomy and analyzed for mucosa and muscularis thickness, connective tissue synthesis, and degradation. Serum levels of estrone and 17ß-estradiol were analyzed at baseline and the day of surgery using highly sensitive liquid chromatography-tandem mass spectrometry. RESULTS: Fifteen women per group (n = 30 total) were randomized; 13 per group underwent surgery. Among drug-adherent participants (n = 8 estrogen, n = 13 placebo), epithelial and muscularis thickness was increased 1.8- and 2.7-fold (P = .002 and P =.088, respectively) by estrogen. Collagen types 1α1 and 1α2 mRNA increased 6.0- and 1.8-fold in the vaginal muscularis (P < .05 for both); collagen type Ia protein increased 9-fold in the muscularis (P = .012), whereas collagen III was not changed significantly. MMP-12 (human macrophage elastase) mRNA was suppressed in the vaginal mucosa from estrogen-treated participants (P = .011), and matrix metalloprotease-9 activity was decreased 6-fold in the mucosa and 4-fold in the muscularis (P = .02). Consistent with menopausal norms, serum estrone and 17ß-estradiol were low and did not differ among the two groups. CONCLUSIONS: Vaginal estrogen application for 6 weeks preoperatively increased synthesis of mature collagen, decreased degradative enzyme activity, and increased thickness of the vaginal wall, suggesting this intervention improves both the substrate for suture placement at the time of surgical repair and maintenance of connective tissue integrity of the pelvic floor.

An analysis of two indigenous reproductive health illnesses in a Nahua community in Veracruz, Mexico.

BACKGROUND: This article describes the local concepts indigenous Nahua women hold regarding their reproduction. Specifically it provides a description of two indigenous illnesses--isihuayo and necaxantle, it discusses their etiology, symptoms, and treatments, and it analyzes them within the local ethnomedical framework and sociopolitical context. A perception of female vulnerability is shown to be an underlying shaper of women's experiences of these illnesses. METHODS: This research took place in a small Nahua village in Mexico. Qualitative data on local perceptions of these illnesses were collected by a combination of participant observation and interviews. Ethnobotanical data was obtained through interviews, and medicinal plants were collected in home gardens, fields, stream banks, and forested areas. The total study population consisted of traditional birth attendants (N = 5), clinicians (N = 8), and laywomen (N = 48). RESULTS: Results showed that 20% of the village women had suffered from one or both of these illnesses. The article includes a detailed description of the etiology, symptoms, and treatments of these illnesses. Data shows that they were caused by mechanical, physical, and social factors related to a woman's weakness and/or lack of support. Traditional birth attendants often treated women's illnesses. Five medicinal plants were salient in the treatment of these illnesses: Ocimum basilicum L., Mentzelia aspera L., Pedilanthus tithymaloides (L.) Poit., and Piper umbellatum L. were used for isihuayo, while Solanum wendlandii Hook f. was used for necaxantle. CONCLUSIONS: The research on these two ethnomedical conditions is a useful case study to understanding how indigenous women experience reproductive health. Reproductive health is not simply about clinically-based medicine but is also about how biomedicine intersects with the local bodily concepts. By describing and analyzing indigenous women's ill health, one can focus upon the combination of causes--which extend beyond the physical body and into the larger structure that the women exist in.

Management of chronic vaginal prolapse in an eastern bongo (Tragelaphus eurycerus isaaci).

A 4.5-yr-old multiparous female eastern bongo (Tragelaphus eurycerus isaaci) presented with a prolapsed vagina 4 mo after dystocia and vaginal extraction of a large calf. The prolapse was corrected via manual reduction and vulvoplasty (Caslick operation). A melengesterol acetate contraceptive implant was placed and the bongo was asymptomatic for 6 yr until vaginal prolapse recurrence. The vaginal prolapse recurred four times over a 2-yr span and was managed with repeat Caslick procedures and several epidural injections using 95% grain alcohol. Complications secondary to long-term progestin implant usage, acquired urovagina, as well as perineal atony from the alcohol epidurals are believed to have contributed to prolapse recurrence. Ovariohysterectomy and vaginoplasty ultimately were elected and were curative. According to a survey conducted in response to this case, obstetrical issues and female reproductive tract problems appear to occur sporadically in captive bongo but are not uncommon.

Extensive cervical prolapse during labor: a case report.

BACKGROUND: An extensive, irreducible cervical prolapse during pregnancy is a rare condition and can lead to various complications, including severe cervical edema and dystocia in labor. Treatment options are very limited. CASE: A 33-year-old woman with spina bifida and a history of multiple intraabdominal operations and extensive intraperitoneal adhesions was admitted in labor at 36(6/7) weeks' gestation with an irreducible cervical prolapse. The cervical prolapse was reduced by topical application of concentrated magnesium sulfate. CONCLUSION: In active labor, a prolapsed cervix that is enlarged and edematous can be managed with a topical concentrated magnesium solution to prevent cervical dystocia and lacerations.

Efficacy of tolterodine in women with detrusor overactivity and anterior vaginal wall prolapse: is it the same?

The aim of this study was to assess the efficacy of tolterodine in women with overactive bladder (OAB) and concomitant anterior vaginal prolapse. In this prospective study, 235 consecutive women with OAB symptoms and urodynamic diagnosis of detrusor overactivity who either had no prolapse or had pure anterior vaginal prolapse were included: 184 women (group 1) had no prolapse and 51 women (group 2) had anterior prolapse greater than and equal to stage IIa. Tolterodine 4 mg slow release once a day was prescribed. After 12 weeks, women were reassessed using a 3-point scale (no change, improvement and cured). A total of 158 (85.9%) women in group 1 and 31 (60.8%) women in group 2 reported improvement or cure (P = 0.0002). Women with OAB and significant anterior vaginal prolapse should be informed of a reduced efficacy of antimuscarinics in treating their urinary symptoms.

Molecular analysis of human endometrium: short-term tibolone signaling differs significantly from estrogen and estrogen + progestagen signaling.

Tibolone, a tissue-selective compound with a combination of estrogenic, progestagenic, and androgenic properties, is used as an alternative for estrogen or estrogen plus progesterone hormone therapy for the treatment of symptoms associated with menopause and osteoporosis. The current study compares the endometrial gene expression profiles after short-term (21 days) treatment with tibolone to the profiles after treatment with estradiol-only (E(2)) and E(2) + medroxyprogesterone acetate (E(2) + MPA) in healthy postmenopausal women undergoing hysterectomy for endometrial prolapse. The impact of E(2) treatment on endometrial gene expression (799 genes) was much higher than the effect of tibolone (173 genes) or E(2) + MPA treatment (174 genes). Furthermore, endometrial gene expression profiles after tibolone treatment show a weak similarity to the profiles after E(2) treatment (overlap 72 genes) and even less profile similarity to E(2) + MPA treatment (overlap 17 genes). Interestingly, 95 tibolone-specific genes were identified. Translation of profile similarity into biological processes and pathways showed that ER-mediated downstream processes, such as cell cycle and cell proliferation, are not affected by E2 + MPA, slightly by tibolone, but are significantly affected by E(2). In conclusion, tibolone treatment results in a tibolone-specific gene expression profile in the human endometrium, which shares only limited resemblance to E(2) and even less resemblance to E2 + MPA induced profiles.

The controversies regarding the role of estrogens in urogynecology.

Estrogens are crucial for the proper functioning of genitourinary tract. Hypoestrogenism related to menopause could be linked to numerous disturbances of lower urinary tract. However, the results of most well designed clinical studies do not support use of estrogen or hormone replacement therapy for the treatment of genitourinary symptoms. According to evidence base medicine stress urinary incontinence, overactive bladder syndrome or pelvic organ prolapse are best treated by the surgery or non-hormonal drug therapy.

A thermal burn to a prolapsed uterus.

Burns to the concealed area of the perineum, are relatively rare and usually associated with massive burns and a high mortality rate. A rare case of a thermal burn to a prolapsed uterus is described. The victim was a 72-year-old Bedouin woman, with a 70 per cent total body surface area deep burn from an open fire. In addition to the conventional treatment dictated by such a burn, two unique problems must be considered: (1) the common pathogens of the uterus, Neisseria gonorrhoeae, Chlamydia trachomatis and mycoplasma, are different from those of the skin; (2) the lymphatics of the uterus drain directly into the abdominal cavity and the risk of peritonitis and generalized infection is potentially higher. Intravenous, prophylactic, broad-spectrum antibiotics were therefore initiated immediately following admission. These included: cefoxitin, gentamicin and metronidazole a combination that covers both the potential pathogens of the uterus and the common pathogens of the skin. In addition, and for the same reason, Betadine substituted Flamazine for the local treatment of the exposed uterus. Our patient did not survive the burn, but in a similar, unusual case, the local and systematic remedies must protect against uterine pathogens that are not commonly seen in a burn victim.

Clinical effects of preoperative oestradiol treatment before vaginal repair operation. A double-blind, randomized trial.

The objective of the study was to assess the effects of low-dose vaginal treatment with oestradiol before vaginal operation. In a double-blind randomized study including 43 postmenopausal women scheduled for vaginal repair operation for genital descensus, it was found that 7 patients suffered from concomitant urinary stress incontinence. Vagifem (25 micrograms oestradiol) or placebo was administered as vaginal pessaries daily, 3 weeks prior to surgery and the clinical effects evaluated. One month postoperatively the prevalence of bacteriuria (> 100,000 CFU/ml urine) was significantly lower when using oestradiol than in the placebo group. At follow-up 3 years later 40 women (93%) answered the questionnaires. None received hormone replacement therapy. Nineteen percent in the preoperative oestradiol group and 11% in the preoperative placebo group had had more than two episodes of cystitis treated with antibiotics. This difference is not statistically significant (p > 0.05). Recurrent cystitis was not correlated to bacteriuria postoperatively. Seventy-nine percent of the women with genital prolapse but only 29% of the women with concomitant urinary stress incontinence were cured (p < 0.05). Neither preoperative oestradiol treatment nor body weight had any influence on relapse. Preoperative low-dose vaginal oestradiol treatment may reduce the incidence of bacteriuria in the immediate postoperative period but no long-lasting effects on recurrent cystitis or relapse were seen. Longer-lasting hormone replacement therapy may be necessary to achieve lasting effects.

Intravenous nitroglycerin for uterine relaxation of an inverted uterus.

Intravenous nitroglycerin has recently come to the attention of obstetricians as a potent uterine relaxant. In the case presented, it was used to permit replacement of a tightly contracted, inverted uterus. Relaxation was rapid, effective, and associated with no adverse side effects.

[Puerperal inversion of the uterus]. / Die Inversio uteri puerperalis.

In Europe, one inversion per 25,000 births is expected with present day obstetric management. Faulty management of the third stage of labour may increase the incidence many-fold. North American figures show that the omission of medications during the third stage of labour and traction on the umbilical cord have increased the incidence to 1 in 2,000. Whether cord traction is as free of danger as has been claimed within recent years, needs to be re-evaluated. The classical symptoms and signs of inversion of the uterus are pain, vascular shock and bleeding. If manual reposition of the uterus occurs immediately following the inversion, even without anesthesia, severe complications and post-operative morbidity are low. Following inversion of the uterus, further normal pregnancies can be expected.