Bleeding profile satisfaction and pain and ease of placement with levonorgestrel 19.5 mg IUD: findings from the Kyleena® Satisfaction study.

PURPOSE: To investigate bleeding profile satisfaction and pain and ease of placement with levonorgestrel 19.5 mg IUD in routine clinical practice. METHODS: Women who independently chose levonorgestrel 19.5 mg IUD during routine counselling were invited to participate in this prospective, multinational, observational study. Patient-reported pain and clinician-reported ease of placement were assessed. Bleeding profile satisfaction was evaluated at 12 months/premature end of observation. RESULTS: Most participants (77.8%, n = 878/1129) rated levonorgestrel 19.5 mg IUD placement pain as 'none' or 'mild' and most clinicians (91.1%, n = 1029/1129) rated placement as 'easy'. Pain was more often rated higher in nulliparous compared with parous (p < .0001) and younger (<26 years) compared with older participants (p < .0001), although 67.7% and 69.0% of nulliparous and younger participants respectively reported 'none' or 'mild' pain. Bleeding profile satisfaction at 12 months/end of observation was similar in parous (72.9%, n = 318/436) and nulliparous (69.6%, n = 314/451) participants. Most participants irrespective of age reported bleeding profile satisfaction, ranging from 67.8% (n = 206/304) for 18-25 years to 76.5% (n = 218/285) for >35 years. CONCLUSION: We observed high bleeding profile satisfaction regardless of age or parity with levonorgestrel 19.5 mg IUD and confirmed that device placement is easy and associated with no more than mild pain in most cases in routine clinical practice. Real-world evidence from the Kyleena® Satisfaction Study in routine clinical practice shows high bleeding profile satisfaction with levonorgestrel 19.5 mg IUD regardless of age or parity. IUD placement was easy and associated with little to no pain for most women.

Satisfaction and continuation with LNG-IUS 12: findings from the real-world kyleena® satisfaction study.

PURPOSE: The Kyleena® Satisfaction Study (KYSS) aimed to assess satisfaction and continuation with levonorgestrel-releasing intrauterine system (LNG-IUS) 12 (Kyleena®) in routine clinical practice and to evaluate factors that influence satisfaction. MATERIALS AND METHODS: This prospective, observational, multicentre, single-arm cohort study, with 1-year follow-up, was conducted in Belgium, Canada, Germany, Mexico, Norway, Sweden, Spain and the United States from 2017 to 2018. During routine counselling, women who independently selected to use LNG-IUS 12 were invited to participate in the study. KYSS assessed LNG-IUS 12 satisfaction, continuation and safety. RESULTS: Overall, there were 1126 successful LNG-IUS 12 placements, with insertion attempted in 1129 women. Most participants (833/968, 86.1%, 95% CI 83.7-88.2%, with satisfaction outcome data available) reported satisfaction with LNG-IUS 12 at 12 months (or at the final visit if the device was discontinued prematurely). Satisfaction was not associated with age, parity or motivation for choosing LNG-IUS 12. The majority of women (919/1129, 81.4%) chose to continue after 12 months. Discontinuation was not correlated with age or parity. Overall, 191 women (16.9%) reported a treatment-emergent adverse event. CONCLUSIONS: Results from KYSS provide the first real-world evidence assessing LNG-IUS 12, and demonstrate high satisfaction and continuation rates irrespective of age or parity. Clinical trial registration: NCT03182140.

VCAM-1 on peritoneum and α4ß1 integrin in endometrium and their implications in endometriosis.

The objective of the study is to investigate vascular cellular adhesion molecule-1 (VCAM-1) expression on peritoneal mesothelial cells and α4ß1 integrin on eutopic endometrium as possible mechanisms in the pathogenesis of endometriosis. It is a case-control study carried out at an academic medical center. Participants are patients with (n=9) and without (n=15) endometriosis. The main outcome measures included VCAM-1 expression on peritoneal mesothelial cells and α4ß1 expression on eutopic endometrium using immunohistochemistry and flow cytometry, respectively. Patients with endometriosis were more likely to express VCAM-1 on peritoneal mesothelial cells, both in areas with and without macroscopic disease, compared with patients without endometriosis (9/9 vs. 3/15, P<0.001). No differences were found between cases and controls in regards to eutopic endometrial expression of α4ß1 integrin. The presence of VCAM-1 on peritoneal mesothelial cells is associated with endometriosis. This field effect, in addition to the similarity found with regards to the expression of α4ß1 integrin in eutopic endometrium between cases and controls, may implicate the expression of VCAM-1 in the peritoneum, and not changes in the eutopic endometrium, as a contributor to the pathogenesis of endometriosis.

Sexual function in women with polycystic ovary syndrome.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is a common endocrinologic disorder. Little is known about the effects of PCOS on overall sexual functioning, phases of the sexual response cycle, and sexual satisfaction. AIM: To compare the differences in sexual function between women with PCOS and controls, and to assess the relationship of serum testosterone, body mass index (BMI), hirsutism, and acne with sexual function scores in women with PCOS. METHODS: A cross-sectional analysis in which women who met the National Institute of Child Health and Human Development criteria for PCOS were compared with a group of healthy volunteers. MAIN OUTCOME MEASURES: Results from the validated Changes in Sexual Functioning Questionnaire (CSFQ) were used to assess sexual function. In women with PCOS, serum testosterone levels, BMI, self-reported hirsutism, and acne were assessed as independent variables. RESULTS: Ninety-two women with PCOS and 82 controls were studied. Based on total CSFQ scores, sexual dysfunction was present in 27.2% of cases vs. 24.4% of controls (not signifcant). Women with PCOS had a significantly lower orgasm/completion score compared with women in the control group (P < 0.001). Women with PCOS whose testosterone levels were >1 standard deviation above the mean had significantly better sexual functioning vs. those within 1 SD (P = 0.015) and those >1 SD below the mean (P = 0.033). In women with PCOS, increasing BMI was associated with a significant reduction in the orgasm/completion subdomain, but no significant associations were found in regard to acne or hirsutism. CONCLUSIONS: Women with PCOS have similar sexual functioning scores compared with controls except in regard to orgasm/completion. The subpopulation of women with PCOS whose serum testosterone levels are in the normal reproductive range are at increased risk for sexual dysfunction.

What Is New in Endometriosis?: Best Articles of the Past Year.

This month we focus on current research in endometriosis. Dr. Stovall discusses four recent publications, which are concluded with a "bottom-line" that is the take-home message. A complete reference for each can be found in on this page along with direct links to the abstracts.

The effects of combined raloxifene and oral estrogen on vasomotor symptoms and endometrial safety.

OBJECTIVE: To compare effects of 52 weeks' treatment with either raloxifene 60 mg/day alone (RLX) or in combination with 17beta-estradiol 1 mg/day (RLX + E) on vasomotor symptoms (n = 83) and endometrial safety (n = 123) in postmenopausal women who transitioned from estrogen-progestin therapy. DESIGN: In this randomized, double-blind clinical trial, the frequency of vasomotor symptoms, hot flashes, and night sweats was assessed for up to 52 weeks. Endometrial thickness was assessed by transvaginal ultrasonography at baseline and at 12 and 52 weeks. An exit endometrial biopsy was performed at study completion or early termination. RESULTS: The frequency of vasomotor symptoms, hot flashes, and night sweats was unchanged from baseline with RLX but was significantly reduced in women treated with RLX + E, from baseline (all P < 0.001) and the RLX group at 6, 12, 24, 36, and 52 weeks (all P < 0.01). Women in the RLX + E group had significantly increased endometrial thickness (0.74 +/- 0.28 mm, mean +/- SEM) at 52 weeks, from baseline and RLX (P < 0.05), with no statistically significant changes in women treated with RLX. Two women, both in the RLX + E group, had endometrial hyperplasia (one with atypia) on the exit biopsy. CONCLUSIONS: In women transitioning from estrogen-progestin therapy, occurrence of vasomotor symptoms was unchanged from baseline with RLX treatment, but these symptoms were significantly reduced with combined RLX + E therapy. Signs of endometrial stimulation were observed in the RLX + E group. Further studies using different estrogen doses and preparations are needed before concomitant use of raloxifene with systemic estrogens can be recommended.

Primary and preventive healthcare in obstetrics and gynecology: a study of practice patterns in the mid-atlantic region.

OBJECTIVES: To assess the current perspective of regional obstetrician/gynecologists on providing primary/preventive healthcare, including their desire to provide primary care in their practices and whether or not they are adequately trained as primary care providers. METHODS: A self-administered survey with a Likert scale that included demographic information and questions about the practice of primary healthcare was mailed to regional obstetrician/gynecologists both in practice and in residency training. RESULTS: One hundred thirty-nine physicians responded to the survey (33% response rate). Respondents were divided (48% agreed vs. 52% disagreed) when asked if obstetrician/gynecologists should be considered primary healthcare providers. When asked if they viewed themselves as specialists who also provide primary care for women, the majority of physicians (62%) agreed. The majority of physicians (64%) disagreed when asked if they wanted to include primary care in their practice. When asked if they thought that they were adequately trained to provide primary healthcare, respondents were divided (47% agreed vs. 53% disagreed). However, a significant gender difference was found between respondents, with male physicians being more likely than female physicians to agree (55% vs. 33%, p < 0.05) when asked if they were adequately trained to provide primary care. CONCLUSIONS: In this regional study of obstetrician/gynecologists, physician opinions were divided regarding their status as primary care providers, but the majority of respondents did not want to include primary healthcare in their practice. A significant gender difference exists between physicians with regard to the question of adequate training for primary care, with male obstetrician/gynecologists being more likely as to agree that they are adequately trained to provide primary care.

Laparoscopy training in United States obstetric and gynecology residency programs.

OBJECTIVES: To assess laparoscopic training curriculums in US Obstetrics and Gynecology residency programs. METHODS: A list of E-mail addresses was obtained for the accredited Obstetrics and Gynecology residency programs in the US from the CREOG Directory of Obstetric-Gynecologic Residency Programs and Directors. An E-mail survey containing 8 questions regarding laparoscopy training was sent to all residency directors with current E-mail addresses. RESULTS: Seventy-four residency directors responded to the survey for a response rate of 41%. Residency programs from all sections of the US were included in the study. Results of the survey indicate that 69% of residency programs had implemented a formal laparoscopy training program. At least half of the program directors surveyed stated that lack of faculty time and funds were the main barriers to laparoscopic surgery training. Seventy-two percent of those surveyed thought that in the future the health-care industry would demand proof of competency in laparoscopy as standard of care. CONCLUSIONS: Most US Obstetrics and Gynecology residency programs have implemented a formal laparoscopy training curriculum, use more than one method to train their residents, and involve almost half of their faculty on average in training residents to perform laparoscopic surgery.

What Is New in Estrogen Agonists and Antagonists?: Best Articles From the Past Year.

This month we focus on current research in estrogen agonists and antagonists. Dr. Stovall discusses four recent publications, which are concluded with a "bottom line" that is the take-home message. The complete reference for each can be found in Box 1 on this page, along with direct links to the abstracts.

Pelvic pedicled omental flaps and autologous free omental grafts in a rabbit model.

BACKGROUND: There is a need to identify an inexpensive, effective method to prevent postoperative adhesion formation. The objective of this study was to create a novel model for studying omentum as a pelvic adhesion barrier. Randomized, prospective, controlled surgical intervention with serial follow-up in 16 female rabbits at a University-based Center for Comparative Medicine. Interventions included bilateral hysterotomy incision and repair. The left hysterotomy was randomized into coverage with an omental flap or graft; the right hysterotomy remained uncovered. Adhesions were scored via laparoscopy on postoperative days 2, 4, 8, and 12; postmortem evaluation and scoring took place on postoperative day 16. Statistical tests consisted of Kappa tests of agreement between adhesion scorers and Kruskal-Wallis nonparametric tests for the comparison of adhesion scores by intervention arm and by uterine horn. RESULTS: All omental flaps and grafts survived. The only significant difference in mean adhesion scores was seen in non-hysterotomy-associated adhesions, where grafts had a lower score than flaps (p = 0.03). CONCLUSIONS: Survival of all omental flaps and grafts demonstrates that this is a practical model for studying omentum as a pelvic adhesion barrier. Determining the efficacy of omentum as a pelvic adhesion barrier will require further investigation.

Menopausal symptoms in older women and the effects of treatment with hormone therapy.

OBJECTIVE: In some women, hot flashes and other symptoms attributed to menopause persist for many years after the cessation of menses. The frequency and severity of such symptoms and response to hormone therapy in older women have not been well documented. METHODS: We used data from the Heart and Estrogen/Progestin Replacement Study, a blinded, clinical trial among 2763 women with documented coronary disease and a uterus who were randomized to receive either conjugated estrogens 0.625 mg plus medroxyprogesterone acetate 2.5 mg in one tablet or placebo. Participants were queried at baseline and annually regarding menopausal symptoms. Breast symptoms were self-reported, and uterine bleeding was recorded on a daily diary. RESULTS: Symptoms associated with menopause were relatively common among Heart and Estrogen/Progestin Replacement Study participants, whose average age was 67 years and who averaged 18 years since menopause. At baseline, 16% of women reported frequent hot flashes, 26% vaginal dryness, 10% genital irritation, 55% trouble sleeping, and 53% early awakening. Women assigned to hormone therapy reported less frequent hot flashes, vaginal dryness, and trouble sleeping compared with women assigned to placebo, but more frequent vaginal discharge, genital irritation, uterine bleeding, and breast symptoms. The reporting of breast symptoms among women in the hormone group decreased from 40% at 1 year to 13% by the 4th year. Uterine bleeding was reported by 31% and spotting by an additional 33% of women in the hormone group during the 1st year of treatment; by the 4th year, these proportions had fallen to 11% and 20%, respectively. CONCLUSION: Symptoms typically attributed to menopause are common in elderly women. Postmenopausal hormone therapy reduces hot flashes, trouble sleeping, and vaginal dryness, but at standard doses in elderly women is associated with vaginal discharge, genital irritation, uterine bleeding, and breast symptoms.

Effects of age, parity, and device type on complications and discontinuation of intrauterine devices.

OBJECTIVE: To conduct an analysis of intrauterine device (IUD)-related outcomes including expulsion, contraceptive failure, and early discontinuation and to compare these outcomes in regard to age, parity, and IUD type. METHODS: This was a multicenter retrospective chart review of adolescents and women aged 13-35 years who had an IUD inserted for contraception between June 2008 and June 2011. RESULTS: A total of 2,523 patients' charts were reviewed. Of these, 2,138 patients were included in our analysis. After a mean follow-up of 37±11 months, the overall rates of IUD expulsion and pregnancy were 6% and 1%, respectively, and were not significantly different by age or parity. Intrauterine device discontinuation rates were 19% at 12 months and 41% after a mean follow-up of 37 months. Despite similar rates of IUD discontinuation between age groups at 12 months of use, teenagers and young women aged 13-19 years were more likely to request early discontinuation at the end of the total follow-up period. No significant difference was noted in pelvic inflammatory disease rates (2%) based on age. After adjusting for age and parity, we found that copper IUD users were more likely to experience expulsion and contraception failure compared with levonorgestrel intrauterine system users (hazard ratios 1.62, 95% confidence interval [CI] 1.06-2.50 and hazard ratios 4.89, 95% CI 2.02-11.80, respectively). CONCLUSION: Similar to adults, IUD use in adolescents and nulliparous women is effective and associated with low rates of serious complications. Health practitioners should therefore consider IUDs for contraception in all females. Teenagers and young women are more likely to request premature discontinuation of their IUDs and may benefit from additional counseling.

Persistence with oral contraceptive pills versus metformin in women with polycystic ovary syndrome.

OBJECTIVE: We studied patient persistence with oral contraceptive pills (OCPs) compared to metformin for treatment of polycystic ovary syndrome (PCOS) in an urban university clinic population. METHODS: We conducted a retrospective cohort study of women with PCOS who were treated in our specialty clinic between 2004 and 2006. All women with the diagnosis of PCOS, defined as oligomenorrhea or amenorrhea in conjunction with clinical or biochemical evidence of hyperandrogenism, with exclusion of other causes, were included in the study. We abstracted data on demographic characteristics, medical history, anthropometrical measures, desire for pregnancy, prescribed treatment, and patient report of persistence with treatment at 3, 6, and 12 months. The primary outcome measure was persistence with prescribed treatment. RESULTS: One hundred nineteen subjects were included in the study. Demographic and anthropometrical characteristics were similar between the groups. At 3 months, 57.1% were persistent with OCPs, and 57.8% were persistent with metformin (p=0.93). At 6 months, the percentages dropped to 38.1% with OCPs and 43.9% with metformin (p=0.46). At 12 months, only 21.7% continued with OCPs compared to 31.2% with metformin (p=0.19). Subjects were significantly more likely to be persistent with either OCPs or metformin at 3 months compared to either 6 or 12 months (p<0.01). CONCLUSIONS: Women with PCOS showed similar persistence rates with OCPs compared to metformin. Persistence with either treatment precipitously decreases over time and is modest at 12 months.

Perioperative evaluation in Herlyn-Werner-Wunderlich syndrome.

BACKGROUND: Herlyn-Werner-Wunderlich syndrome is defined by uterine didelphys, obstructed hemivagina, and ipsilateral renal agenesis. We report the presentation, radiographic findings, and outcomes of three patients with Herlyn-Werner-Wunderlich syndrome who underwent surgical management at a tertiary care academic medical center. CASES: Two patients were diagnosed by magnetic resonance imaging and one by ultrasonography. All three underwent successful transvaginal septoplasty and drainage of the hematocolpos and hematometra. One required septoplasty revision with temporary vaginal stent placement. CONCLUSION: Herlyn-Werner-Wunderlich syndrome is a rare condition. The most urgent concern is the obstruction of menstrual effluent. Unlike an isolated transverse vaginal septum, the vaginal septum with Herlyn-Werner-Wunderlich syndrome is parallel to the patent vaginal canal, less pliable, and closer to the cervix. These anatomical differences result in pronounced distortion with significant diagnostic and surgical challenges.

Alternatives to hysterectomy: focus on global endometrial ablation, uterine fibroid embolization, and magnetic resonance-guided focused ultrasound.

The aim of this study was to inform the clinician of alternatives to hysterectomy through a critical evaluation of three treatment options: global endometrial ablation, uterine fibroid embolization, and magnetic resonance-guided focused ultrasound. Studies published in English-language, peer-reviewed journals were systematically searched using Cochrane and Medline. Keywords used included "alternatives to hysterectomy," "endometrial ablation," "uterine fibroid embolization," "uterine artery embolization," and "focused ultrasound." Articles meeting the inclusion criteria were reviewed and analyzed for themes and similarities. All three alternative methods of treatment reviewed are currently approved for use in the United States and abroad. In fact, five different global endometrial ablation devices are approved by the Food and Drug Administration for treatment of menorrhagia. Patient satisfaction scores after endometrial ablation are high (90%-95%), but amenorrhea rates are much lower (15%-60%). Data from randomized trials demonstrate that uterine fibroid embolization results in a shorter hospital stay and quicker return to work as compared with abdominal hysterectomy for leiomyomas, but after embolization, up to 20% of women need a second procedure. Ex-ablative therapy of leiomyomas with focused ultrasound is the newest of the three methods. It has a special set of patient selection criteria and is only available at less than 20 medical centers in the United States. Leiomyoma symptom relief after focused ultrasound therapy at 1 year post-procedure is high (85%-95%). There are many effective alternatives to hysterectomy in women with menorrhagia and/or symptomatic leiomyomas. However, because these procedures are performed by individuals from different subspecialists, primarily gynecologists and interventional radiologists, clinicians must consider using a multidisciplinary approach to find the best procedure for a given patient. There are no randomized trials comparing uterine fibroid embolization to vaginal hysterectomy, laparoscopic hysterectomy, or laparoscopic myomectomy.

Tissue-selective estrogen complex bazedoxifene and conjugated estrogens for the treatment of menopausal vasomotor symptoms.

Menopause occurs on average at age 51.4 years. Most, but not all, women who undergo menopause experience significant vasomotor symptoms (VMS). Although single agent estrogen therapy can relieve VMS, over time estrogen can stimulate the endometrial lining leading to an increased risk for endometrial hyperplasia and adenocarcinoma. Although a progestin has traditionally been given in combination with estrogen to 'protect' the endometrium, a new and innovative approach to this traditional combination hormone therapy is to substitute the progestin with an alternative agent. One such alternative agent is bazedoxifene, an estrogen agonist-antagonist. Based on data from randomized trials, when bazedoxifene is given in combination with oral conjugated estrogens to post-menopausal women, the risk of estrogen-associated endometrial stimulation is significantly reduced. The combination of bazedoxifene and conjugated estrogens has also been shown to relieve menopause-associated VMS and vaginal atrophy, and has been shown to be safe for short-term use. Long-term studies of this combination are needed to determine if the combination of conjugated estrogens/bazedoxifene can be used for >3 years without increasing the risk of breast cancer, stroke, cognitive deficit, pulmonary embolism or coronary heart disease. Short-term data regarding this combination has been submitted to the FDA and is currently under review for clinical use, with the relief of VMS as its primary indication. Data regarding the effects of combination conjugated estrogens/bazedoxifene therapy on bone are promising in terms of the prevention and treatment of post-menopausal osteoporosis.

Effect of combined metformin and oral contraceptive therapy on metabolic factors and endothelial function in overweight and obese women with polycystic ovary syndrome.

In this randomized, double-blind, placebo-controlled study, 19 overweight women with polycystic ovary syndrome were randomized to a 3-month course of either metformin plus combined hormonal oral contraceptive (OC) (n = 9) or OC plus matched placebo (n = 10). After 3 months, both treatments had similar effects on androgen levels, lipid profile, insulin sensitivity, and serum inflammatory markers, but flow-mediated dilatation increased by 69.0% in the metformin plus OC group while it remained unchanged in the OC group. CLINICAL TRIAL REGISTRATION NO: NCT00682890.

Aprela, a single tablet formulation of bazedoxifene and conjugated equine estrogens (Premarin) for the potential treatment of menopausal symptoms.

Aprela, in development by Pfizer Inc, is a once-daily, orally administered, tissue-selective estrogen complex that contains the selective estrogen receptor modulator bazedoxifene (BZA) and conjugated equine estrogens (CE). Aprela was designed as an alternative to combination estrogen and progestin therapy to treat the vasomotor symptoms associated with menopause without the potential safety concerns associated with combination estrogen/progestin therapy, and with better tolerability. Both estrogens and BZA bind to estrogen receptors (ER)alpha and beta, but when BZA binds to an ER, the result may be an estrogen agonistic or antagonistic effect. In contrast, progestins antagonize the effects of estrogen in the uterus, but along with estrogen, stimulate breast tissue increasing the risk for breast cancer. In phase III clinical trials, Aprela significantly reduced the number and severity of vasomotor symptoms, reduced vaginal atrophy and increased bone mineral density. However, higher doses of BZA tended to attenuate these positive effects of CE. At the time of publication, there were no clinical data from women taking Aprela for > 2 years, and no definitive trials to determine the effects of Aprela on the risks for cardiovascular events, stroke, breast cancer, venous thromboembolism or cognitive function had been completed. Nevertheless, at the time of publication, Aprela was under consideration by the FDA for approval to treat vasomotor symptoms in postmenopausal women.