Carlos Alberto Petta

Prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 18) L1 virus-like particle vaccine in young women: a randomised double-blind placebo-controlled multicentre phase II efficacy trial

BACKGROUND A randomised double-blind placebo-controlled phase II study was done to assess the efficacy of a prophylactic quadrivalent vaccine targeting the human papillomavirus (HPV) types associated with 70% of cervical cancers (types 16 and 18) and with 90% of genital warts (types 6 and 11). METHODS 277 young women (mean age 20.2 years [SD 1.7]) were randomly assigned to quadrivalent HPV (20 microg type 6, 40 microg type 11, 40 microg type 16, and 20 microg type 18) L1 virus-like-particle (VLP) vaccine and 275 (mean age 20.0 years [1.7]) to one of two placebo preparations at day 1, month 2, and month 6. For 36 months, participants underwent regular gynaecological examinations, cervicovaginal sampling for HPV DNA, testing for serum antibodies to HPV, and Pap testing. The primary endpoint was the combined incidence of infection with HPV 6, 11, 16, or 18, or cervical or external genital disease (ie, persistent HPV infection, HPV detection at the last recorded visit, cervical intraepithelial neoplasia, cervical cancer, or external genital lesions caused by the HPV types in the vaccine). Main analyses were done per protocol. FINDINGS Combined incidence of persistent infection or disease with HPV 6, 11, 16, or 18 fell by 90% (95% CI 71-97, p<0.0001) in those assigned vaccine compared with those assigned placebo. INTERPRETATION A vaccine targeting HPV types 6, 11, 16, 18 could substantially reduce the acquisition of infection and clinical disease caused by common HPV types.

High sustained efficacy of a prophylactic quadrivalent human papillomavirus types 6/11/16/18 L1 virus-like particle vaccine through 5 years of follow-up

Human papillomavirus (HPV) causes cervical, vulvar, and vaginal cancers, precancerous dysplasia, and genital warts. We report data for the longest efficacy evaluation to date of a prophylactic HPV vaccine. In total, 552 women (16–23 years) were enrolled in a randomised, placebo-controlled study of a quadrivalent HPV 6/11/16/18 L1 virus-like-particle vaccine with vaccination at months 0, 2, and 6. At regular intervals through 3 years, subjects underwent gynaecologic examination, cervicovaginal sampling for HPV DNA, serum anti-HPV testing, and Pap testing, with follow-up biopsy as indicated. A subset of 241 subjects underwent two further years of follow-up. At 5 years post enrolment, the combined incidence of HPV 6/11/16/18-related persistent infection or disease was reduced in vaccine-recipients by 96% (two cases vaccine versus 46 placebo). There were no cases of HPV 6/11/16/18-related precancerous cervical dysplasia or genital warts in vaccine recipients, and six cases in placebo recipients (efficacy=100%; 95% CI:12–100%). Through 5 years, vaccine-induced anti-HPV geometric mean titres remained at or above those following natural infection. In conclusion, a prophylactic quadrivalent HPV vaccine was effective through 5 years for prevention of persistent infection and disease caused by HPV 6/11/16/18. This duration supports vaccination of adolescents and young adults, which is expected to greatly reduce the burden of cervical and genital cancers, precancerous dysplasia, and genital warts.

Bleeding patterns and clinical performance of the levonorgestrel-releasing intrauterine system (Mirena) up to two years.

The objectives of this study were to evaluate the bleeding patterns and clinical performance during the first 2 years of use of an intrauterine system releasing 20 microg/day of levonorgestrel (LNG-IUS, Mirena). Two-hundred-fifty-six women accepted use of Mirena from April 1998 through September 1998. The gross cumulative discontinuation rate due to pregnancy and expulsion were significantly higher in women who used the device because of heavy bleeding. There was one pregnancy at the 15th month of use after an inadvertent expulsion of the device. The continuation rate was 66.2 at the end of the second year. Forty-four percent of women reported amenorrhea at the 6th month of use. This rate maintained stability at 50% after 12 and 24 months of use. Spotting was present in 25% of the users at 6 months, decreasing to 8% and 11% at 18 and 24 months, respectively. Oligomenorrhea was described by one-quarter of women and was similar at each observation period. Removals due to menstrual bleeding problems were concentrated in the first 6 months of use and mostly due to amenorrhea or menorrhagia. In conclusion, LNG-IUS showed a high contraceptive efficacy and a good continuation rate up to 2 years. In addition, a reduction of blood loss was observed a few months after insertion.

Depression in women with endometriosis with and without chronic pelvic pain

Aim. The aim of the study is to compare the prevalence of depression in women surgically diagnosed with endometriosis according to the presence or absence of pelvic pain. Methods. This cross‐sectional prospective study evaluated 100 women receiving care at the Outpatients’ Clinic for Endometriosis, Department of Obstetrics and Gynecology, Universidade Estadual de Campinas (UNICAMP), Campinas, São Paulo, Brazil, equally divided into two groups: one suffering from chronic pelvic pain and the other pain‐free. The Beck Depression Inventory was used in order to measure depression. Results. Depression was detected in 86 and 38% of the women with and without chronic pelvic pain, respectively. Complaints of depression, such as somatic concerns, work inhibition, dissatisfaction, and sadness, were observed at a significantly higher rate in the group with pain. A sensation of failure was the only variable observed more frequently in the pain‐free group. Conclusions. Depression is highly prevalent in women with endometriosis, especially those with pelvic pain. Careful evaluation can identify women with depression who may benefit from treatment.

Salivary cortisol concentrations, stress and quality of life in women with endometriosis and chronic pelvic pain

The objective of this study was to evaluate the perceived stress index, quality of life, and hypothalamus-pituitary-adrenal axis activity in women with endometriosis and chronic pelvic pain. For the study, 93 women with endometriosis and 82 healthy women volunteered. The visual analogue scale (VAS) (0 = no pain; 10 = severe pain) was used to determine pain intensity; the perceived stress questionnaire (PSQ) defined stress index, and the health-related quality-of-life (HRQOL)-SF-36 questionnaire was used to evaluate quality of life. Salivary cortisol was measured at 0800, 1600, and 2000 h and the awakening cortisol response was assessed to evaluate the hypothalamus-pituitary-adrenal axis activity. The results show that women with endometriosis and chronic pelvic pain of moderate intensity (4.1 ± 0.58, mean ± SEM) have higher levels of perceived stress (0.55 ± 0.01 versus 0.42 ± 0.01, p < 0.05), a poorer quality of life expressed as lower scores for all items of the inventory and hypocortisolism. Lower levels of salivary cortisol were observed in all three samples collected, as well as in the awakening cortisol response, for women with endometriosis (0.19 ± 0.09 μg/dl) when compared with controls (0.78 ± 0.08 μg/dl, p < 0.05 l), and it was independent of pain intensity and Mental health (MH) scores in SF-36. We concluded that women with endometriosis and chronic pelvic pain show low concentrations of salivary cortisol and a high level of perceived stress, associated with a poor quality of life. Whether the hypocortisolism was an adaptive response to the aversive symptoms of the disorder or a feature related to the etiology of endometriosis remains to be elucidated.

Rectal endoscopic ultrasound with a radial probe in the assessment of rectovaginal endometriosis.

STUDY OBJECTIVE To evaluate the accuracy of rectal endoscopic ultrasound and to evaluate endometriosis in the rectovaginal septum, rectum, and sigmoid walls. DESIGN Validation of diagnostic test (Canadian Task Force classification II-1). SETTING Tertiary care hospital. PATIENTS Thirty-two consecutive women clinically suspected of having rectovaginal septum endometriosis without previous surgical treatment. INTERVENTION Colonoscopy, transrectal ultrasound, and rectal endoscopic ultrasound, followed by laparoscopy or laparotomy. MEASUREMENTS AND MAIN RESULTS The disease was classified according to 1996 standards of the American Society of Reproductive Medicine. Images obtained by colonoscopy, endoscopic ultrasound, and surgery and histologic findings were compared. In 6 patients endometriosis infiltrated bowel muscularis wall, in 20 it infiltrated rectovaginal septum, and in the remaining 6 there was no evidence of lesions. In all women in whom infiltration of the intestinal wall was suspected, rectal endoscopic ultrasound and colonoscopy confirmed the lesions (sensitivity 100%, specificity 67%). CONCLUSION Endoscopic ultrasound was useful in preoperative assessment of women with endometriosis.

Therapeutic use of levonorgestrel-releasing intrauterine system in women with menorrhagia: a pilot study

The objective of this study was to evaluate the efficacy and performance, for up to 1 year, of an intrauterine system releasing 20 microg/day of levonorgestrel (LNG-IUS, Mirena) in the treatment of women with menorrhagia. It was a descriptive, prospective, non-comparative study. A 20 microg/day LNG-releasing-IUS was inserted on any day during bleeding to 44 women (between 24 and 49 years of age) who presented with menorrhagia after medical therapies had failed. Menstrual patterns were assessed, and hemoglobin concentrations were measured before LNG-IUS was inserted and at 3, 6, 9, and 12 months of use. The most common bleeding pattern at 3 months after insertion was spotting, and after 6, 9, and 12 months the majority of women presented with amenorrhea or oligomenorrhea. Three women requested removal of the LNG-IUS because of spotting, and six women expelled it spontaneously. Hemoglobin levels were improved from 102 g/L to 123 and 128 g/L at 3 and 12 months, respectively, after insertion of the LNG-IUS (p < 0.01). At 12 months 79.5% of participants continued the use of LNG-IUS. In conclusion, LNG-IUS was an effective treatment for three out of four women with menorrhagia and could be an alternative treatment for women with menorrhagia who are either contraindicated for or refuse hysterectomy or endometrial ablation.

Forearm bone density in users of Depo-Provera as a contraceptive method

OBJECTIVE To determine the influence of depot medroxyprogesterone acetate (MPA) on bone mineral density when used as a contraceptive method. DESIGN Cross-sectional study. SETTING Academic tertiary-care hospital. PATIENT(S) Fifty premenopausal women who had used depot MPA as a contraceptive method for > or =1 year and 50 women who had never used hormonal contraceptive methods. INTERVENTION(S) Bone mineral density was evaluated at the midshaft and at the distal radius of the nondominant forearm using single x-ray absorptiometry. MAIN OUTCOME MEASURE(S) Bone mineral density. RESULT(S) Bone mineral density at the midshaft of the forearm was lower in depot MPA users than in women who had never used hormonal contraceptive methods, but the difference was not statistically significant. At the distal portion, bone mineral density was significantly lower in the study group. The duration of depot MPA use was not related to bone mineral density. CONCLUSION(S) Women > or =35 years of age presented with a lower bone mineral density only at the distal portion of the forearm after the use of depot MPA for > or =1 year. However, this decrease was not related to the duration of depot MPA use. It is not possible to conclude that women who use depot MPA are at risk of osteoporosis.

Vascular endothelial growth factor concentrations in the serum and peritoneal fluid of women with endometriosis

Objectives: To investigate whether there is an association between vascular endothelial growth factor (VEGF) levels in serum and peritoneal fluid, and the presence of pelvic endometriosis and its clinical symptoms. Methods: Blood and peritoneal fluid sample levels of VEGF were measured in 46 women undergoing laparoscopy: 32 with suspected endometriosis and 14 with confirmed endometriosis. Data were analyzed according to phase of the menstrual cycle, symptoms, disease stage, and disease site. Results: There were no significant associations between serum and peritoneal fluid levels of VEGF and the presence of endometriosis, even when controlling for the menstrual phase. However, among the women with confirmed endometriosis, there was a significant increase (P = 0.002) in the mean peritoneal VEGF level in those in the late secretory phase compared with those in the proliferative and early secretory phases. Conclusions: Measuring VEGF levels in symptomatic patients is not helpful to differentiate those with endometriosis from those with a different condition. However, in the late secretory and menstrual phases, mean VEGF levels were higher in women with confirmed endometriosis than in those suspected of having the disease.

Forearm bone density in long-term users of oral combined contraceptives and depot medroxyprogesterone acetate.

OBJECTIVE To compare the bone mineral density of users of combined oral contraceptives (OC) or depot medroxyprogesterone acetate (depot-MPA) with women who have never used a hormonal contraceptive method. DESIGN Cross-sectional study. SETTING Academic tertiary-care hospital. PATIENT(S) A total of 189 women, aged 30 to 34 years old, were allocated to three groups: 63 who had used OC for at least 2 years; 63 who had used depot-MPA for at least 2 years; and 63 control women who had never used hormonal contraceptives. INTERVENTION(S) Each womans bone mineral density (BMD) was evaluated at the distal and ultradistal section of the radius of the nondominant forearm by the use of single x-ray absorptiometry. MAIN OUTCOME MEASURE(S) We obtained BMD measurements for each participant. RESULT(S) Independent of the period of use and the section of the forearm studied, we found no difference in BMD for OC or depot-MPA users when compared to women who had never used hormonal contraceptive methods. In addition, BMD was similar between OC users and depot-MPA users. The multiple linear regression analysis showed that the variables associated with BMD were weight, number of pregnancies, and the womans occupation. CONCLUSION(S) Women aged 30 to 34 years who have used OC or depot-MPA have similar BMD as control women. These findings suggest that the use of OC or depot-MPA does not affect the BMD of women in this age group.