Endometrial effects, bleeding control, and compliance with a new postmenopausal hormone therapy regimen based on transdermal estradiol gel and every-other-day vaginal progesterone in capsules: a 3-year pilot study

In a 3-year prospective study, 30 postmenopausal women received transdermal E2 gel and every-other-day vaginal P in capsules. At study completion, endometrial thickness was significantly reduced as compared with baseline (2.7 +/- 0.5 vs. 3.4 +/- 0.9 mm), endometrial biopsy showed endometrial atrophy in all cases, and amenorrhea was achieved in 92.6% of cycles, while excellent patient satisfaction was achieved.     

Symptomatic vaginal bleeding in a postmenopausal woman: a case report of pancreatic adenocarcinoma metastasizing exclusively to the vagina

Although primary vaginal cancer is uncommon, representing 1-2% of all female genital malignancies, metastatic disease to the vagina is not. Most cases represent metastases from other pelvic organs or the colon. We present the second case in the literature of a pancreatic adenocarcinoma metastasizing exclusively to the vagina.     

Safety and efficacy of tibolone and menopausal transition: a randomized,double-blind placebo-controlled trial

Objective: To evaluate the efficacy, safety and tolerability of Tibolone use during the menopausal transition (MT). Methods: Sixty-five healthy women aged 40–55 years (48.5?±?3.5 years) were recruited for a randomized, double-blind controlled trial. Thirty participants were recruited to receive oral Tibolone 2.5?mg/day – Tibolone Group (TG), and 35 participants were assigned to the Placebo Group (PG), which received one capsule of lactose/day. Both groups were treated for 12 consecutive weeks. The Blatt-Kupperman Menopausal Index (KMI) and the Greene Climacteric Scale (GCS) were used. The glycaemic and lipid profiles, biochemical measures of hepatic function and endometrial thickness were measured for safety. A daily registry of complaints related to the treatment was maintained, and anthropometric measures were obtained to assess tolerability. Results: A total of 57 women completed the study. After 12 weeks of Tibolone use, the total score and percentage of the KMI and GCS were significantly decreased compared to baseline, which reflected the efficacy of the treatment of climacteric symptoms. The improvement in blood biochemistry, endometrial atrophy and maintenance of the anthropometrical measures reflected the safety of Tibolone use. The absence of serious side effects demonstrated good tolerability for Tibolone use. Conclusions: The results showed good efficacy, tolerability and safety of Tibolone use during the MT.     

Effects of tibolone and continuous combined hormone replacement therapy on bleeding rates,quality of life and tolerability in postmenopausal women

Objective To compare the effects of tibolone and conjugated equine oestrogens continuously combined with medroxyprogesterone acetate on bleeding rates, quality of life (QoL) and tolerability.
Design A double-blind, randomised comparative trial.
Setting Thirty-seven centres in six European countries.
Population Five hundred and one postmenopausal women, under 65 years of age with an intact uterus.
Interventions For 12 months, women received daily treatment with tibolone 2.5 mg (   n = 250  ), or conjugated equine oestrogens 0.625 mg continuously combined with medroxyprogesterone acetate 5 mg (CEE–MPA,   n = 251  ).
Main outcome measures The primary outcome was vaginal bleeding rate during cycles 4–6. The secondary outcomes were vaginal bleeding rate during cycles 1–3, 7–9 and 10–13, cumulative bleeding rate, QoL, wellbeing, climacteric symptoms, urogenital complaints and tolerability.
Results Treatment with tibolone led to a significantly lower bleeding rate during cycles 4–6 compared with CEE–MPA (15.0% vs 26.9%;   P = 0.004  ); there was a similar difference during cycles 1–3. Both treatments improved QoL, wellbeing, climacteric symptoms and urogenital complaints. By intent-to-treat analysis, tibolone significantly improved sexual drive, interest and/or performance, compared with CEE–MPA at 12 months (   P = 0.017  ). Although both treatments were well tolerated, there was a significantly lower incidence of breast tenderness with tibolone than CEE–MPA (2.4% vs 17.1%;   P < 0.001  ).
Conclusion The vaginal bleeding rate during cycles 4–6 was significantly lower in women using tibolone. Both treatments improved QoL, wellbeing, climacteric symptoms and urogenital symptoms. Breast tenderness was significantly less frequent with tibolone.     

绝经期激素治疗与阴道疾病

绝经后妇女卵巢内分泌功能减退,体内雌激素水平降低,下生殖道出现萎缩,并引起相关症状,即阴道干涩,外阴阴道刺激和瘙痒以及性交困难等,通常是进行性的。因此,需采用激素治疗以改善妇女绝经后症状,提高生活质量。     

Effects of tibolone and continuous combined hormone therapy on mammographic breast density and breast histochemical markers in postmenopausal women

OBJECTIVE: To compare changes in mammographic density and the expression of markers of proliferation (Ki67) and apoptosis (Bcl-2) after 1 year of treatment with tibolone and continuous conjugated equine estrogens combined with medroxyprogesterone acetate (CEE-MPA). DESIGN: Comparative, randomized, evaluator-blinded study. SETTING: City research hospital. PATIENT(S): Thirty-seven postmenopausal women. INTERVENTION(S): Tibolone (2.5 mg; n = 18) or continuous conjugated estrogens (0.625 mg) combined with medroxyprogesterone acetate (5 mg; n = 19) for 1 year. MAIN OUTCOME MEASURE(S): Mammographic density (BI-RADS density score), expression of immunohistochemical markers Ki67 and Bcl-2. RESULT(S): Mean breast density score decreased significantly from 2.22 to 1.67 in the tibolone group, compared with a significant increase in the CEE-MPA-treated group from 1.84 to 2.63. Ki67 expression decreased in 12 of 15, increased in 2 of 15, and remained unchanged in 1 of 15 subjects in the tibolone group, compared with 1 of 19, 15 of 19, and 3 of 19 subjects, respectively, in the CEE-MPA group. Bcl-2 expression decreased in 12 of 15, increased in 2 of 15, and remained unchanged in 1 of 15 subjects in the tibolone group, compared with 5 of 19, 9 of 19, and 5 of 19 subjects, respectively, in the CEE-MPA group. CONCLUSION(S): One-year treatment with tibolone induced a decrease in breast density, with a reduction in proliferation and a stimulation of apoptosis, whereas 1-year treatment with CEE-MPA induced an increase in breast density, with stimulation of proliferation and inhibition of apoptosis, indicating that tibolone effects on the breast are different from those of CEE-MPA.     

Long-term satisfaction and tolerability with low-dose flutamide: a 20-year surveillance study on 120 hyperandrogenic women

Objective: To evaluate the long-term safety, satisfaction and tolerability of flutamide therapy for female hyperandrogenism.

Design: A 20-year surveillance study.

Methods: Setting: Gynecology Department in a teaching hospital. Patients: Hyperandrogenic women complaining for hirsutism treatment were followed between February 1995 and April 2015. Interventions: Women received flutamide 125 or 250?mg/day alone (n?=?55) or combined with oral contraceptives (n?=?65). Main outcome measures: Adverse events, safety, tolerability satisfaction and efficacy were assessed every 6 months during all the follow-up. Lab tests including liver and lipid profiles were also recorded in each control.

Results: Patients under flutamide therapy showed significant improvements in hirsutism scores after 6 months of treatment with a maximum effect at 12 months that was maintained during all the therapy time. Satisfaction reported by patients with the efficacy of the drug in a visual scale was also high. A total of 54.2 % women presented one or more adverse effects during the follow-up; 33.3% showed at least one adverse effect possibly related with the study drug; and 24.1% withdrew from the study because of adverse effects. During the follow-up, as many as 89.9 % of patients abandoned flutamide. Reasons include: questions linked to medical problems (50%), attempt pregnancy (4%) and significant improvement in the symptomatology (35.8%).

Conclusions: Flutamide is very effective for hirsutism treatment; however, adverse effects are very frequent and affect compliance.     

First trimester vaginal bleeding and adverse pregnancy outcomes among Chinese women: from a large cohort study in China

Objectives: To examine the effect of first trimester vaginal bleeding on adverse pregnancy outcomes including preterm delivery, low birth weight and small for gestational age. Methods: This is a prospective population-based cohort study. A questionnaire survey was conducted on 4342 singleton pregnancies by trained doctors. Binary logistic regression was used to estimate risk ratios (RRs) and 95% con?dence intervals (95% CI). Results: Vaginal bleeding occurred among 1050 pregnant women, the incidence of vaginal bleeding was 24.2%, 37.4% of whom didn’t see a doctor, 62.6% of whom saw a doctor for vaginal bleeding. Binary logistic regression demonstrated that bleeding with seeing a doctor was significantly associated with preterm birth (RR 1.84, 95% CI 1.25–2.69) and bleeding without seeing a doctor was related to increased of low birth weight (RR 2.52, 95% CI 1.34–4.75) and was 1.97-fold increased of small for gestational age (RR 1.97, 95% CI 1.19–3.25). Conclusions: These results suggest that first trimester vaginal bleeding is an increased risk of low birth weight, preterm delivery and small for gestational age. Find ways to reduce the risk of vaginal bleeding and lower vaginal bleeding rate may be helpful to reduce the incidence of preterm birth, low birth weight and small for gestational age.     

Apical vaginal recurrence of ovarian carcinoma: presentation, treatment and survival

The object of this study was to evaluate the incidence, presenting symptoms, treatment, and survival of patients with recurrence of ovarian carcinoma at the vaginal apex. The charts of 19 patients with recurrent ovarian carcinoma at the vaginal apex diagnosed and treated between January, 1971 and December, 1993 were reviewed retrospectively. Statistical analysis was carried out using the nonparametric Wilcoxon rank-sum test and survival rates were calculated using the Kaplan-Meier method. Nineteen of 393 patients (4.8%) with recurrent ovarian carcinoma were found to have recurrent tumor involving the vaginal apex. Nine patients (47%) were symptomatic from the vaginal recurrence: eight patients experienced vaginal bleeding, one had abnormal discharge, and one patient had symptoms related to a rectovaginal fistula in addition to vaginal bleeding. Ten patients (53%) had an asymptomatic mass found on follow-up examination or at the time of second-look laparotomy. Fifteen of 19 patients underwent surgical exploration: eight had recurrent disease isolated to the vaginal apex, four had vaginal apex and pelvic disease, two had disease at the vaginal apex and in the upper abdomen, and one had disease present diffusely throughout the abdomen and pelvis in addition to the vaginal recurrence. Median time from original diagnosis to the diagnosis of a vaginal apical recurrence was 26 months. As of December, 1993, 15 of 19 patients had died of disease and four of 19 patients were alive with disease. The 1-year survival rate from the time of diagnosis of vaginal recurrence was 66% (95% confidence interval: 43–88%); 56% for patients with vaginal bleeding and discharge and 78% for those with asymptomatic masses. Mean survival time was at least 19 months. Patients presenting with a vaginal apex recurrence of ovarian carcinoma should be treated aggressively, especially if symptomatic, since they are likely to survive for at least 1 year following the recurrence.     

An open-label, multicentre trial to evaluate the vaginal bleeding pattern of the combined contraceptive vaginal ring NuvaRing

Objective

The objective of this multicentre, non-controlled, open-label study is the evaluation of the bleeding patterns during the use of a vaginal combined contraceptive, its safety in relation to occurrence of adverse effects, its efficacy as a contraceptive method and user compliance.

Study design

Healthy female volunteers (N = 165), asking for contraception, were enrolled to participate in the study. Each subject was given seven vaginal rings, releasing an average amount of 120 μg etonogestrel (ENG) and 15 μg ethinylestradiol (EE) per day. Study period was 7 cycles. A total of 878 cycles was valid for statistical analysis. The primary parameter, (breakthrough bleeding and/or spotting), was recorded for each cycle. The subjects were asked to report any adverse effect experienced during the treatment period, general physical and gynaecological examinations were performed and haematological blood tests were taken.

Results

Breakthrough bleeding/spotting occurred in 5.01% cycles (44 out of 878 cycles, of whom 37 were breakthrough spotting only). Absence of withdrawal bleeding during the ring-free period was reported in 1.94% cycles (17 out of 878). Forty-one subjects (24.8%) reported 66 events that were potentially drug-related. The most frequently drug-related events were weight increase (10 cases), headache (9 cases), nausea (4 cases). No pregnancy was reported during the study period. Haematology and chemical chemistry tests showed no clinically significant abnormality.

Conclusions

In the present study, NuvaRing^® has shown to be a valid contraceptive method to ensure optimal cycle control with low incidence of irregular bleeding and altered withdrawal bleeding. The low incidence of gastrointestinal side effects (nausea, vomiting) may be related the low hormonal dose and to the vaginal delivery of hormones which avoids the gastrointestinal tract.     

Successful treatment of combined vaginal and broad ligament hematoma using pelvic pressure pack and arterial embolization

The puerperal hematoma,especially broad liga-ment/retroperitoneal hematoma,is a rare but potentiallylethal complication which might not be recognized,of-ten until the parturient has exhibited signs of hypov-olemic shock.Despite the reports of effective manage-ment protocols,retroperitoneal hematoma is still associ-ated with a high mortality rate[1-3].Pelvic pressurepacking after hysterectomy to stop persistent hemor-rhage has been described in the literature[4],but itsrole in puerperal hemorrh…     

Effectiveness,tolerability and acceptance of an oral estradiol/levonorgestrel formulation for the treatment of menopausal complaints: a non-interventional observational study over six cycles of 28 days

Background: Use of hormone therapy for menopausal complaints is a subject of controversy and increased uncertainty and concerns. This non-interventional study aimed to investigate a marketed oral formulation containing 1?mg estradiol and 0.04?mg levonorgestrel for continuous treatment of menopausal symptoms for approximately 6 months in women visiting gynecological practices in Germany.

Methods: Changes in the menopause rating scale (MRS) total and sub-domain scores after three and six 28-d cycles served as primary endpoint. Skin- and hair-related complaints, quality of sexual life and subjective satisfaction with the treatment were assessed. Adverse drug reactions (ADRs), adverse events (AEs) and vaginal bleeding were evaluated.

Results: MRS scores improved significantly above 5 points of clinical relevance as compared to baseline (n?=?736, p?75% of the subjects were amenorrheic throughout the study. Medication's effectiveness and tolerability was rated very good/good by >80% of the participants, who also continued treatment.

Conclusion: This estradiol/low-dose levonorgestrel formulation safely alleviates menopausal symptoms in peri- and postmenopausal women with add-on benefits regarding dermatological and sexual life complaints.     

Insight: prolonged vaginal bleeding during central precocious puberty therapy with a long-acting gonadotropin-releasing hormone agonist: a proposed mechanism and management plan

We have previously described our data collected after administration of gonadotropin releasing hormone-agonist (GnRH-a) to delay sexual maturation, in premenarchal girls suffering from idiopathic central precocious puberty.¹ We have explained the recurrent episodes of bleeding due to discontinuation of the estrogen support of the proliferative and stable endometrium. The recognition in recent years of the extra-pituitary functions of GnRH-a, the ability of GnRH to stimulate prostaglandin production and the known role of prostaglandins in irregular vaginal bleeding prompted us to seek alternative explanations to our data.We suggest considering a potential clinical use of combination therapies of GnRH agonists and prostanoid receptor antagonists to treat central precocious puberty.     

TVT-O和TVT治疗单纯女性压力性尿失禁的疗效对比:立足随机对照试验的Meta分析

目的:系统评价经阴道无张力尿道中段悬吊带术(闭孔路径)(TVT-O)和经阴道无张力尿道中段悬吊带术(TVT)治疗女性压力性尿失禁的客观成功率和并发症发生率。方法:计算机配合手工检索1994年1月~2007年6月各数据库和灰色文献中TVT-O和TVT疗效的随机对照试验(RCT),用Revman4.2.2软件,对两种术式的客观成功率、并发症发生率进行Meta分析。结果:共纳入10个随机对照试验。TVT-O组553例,TVT组575例。Meta分析显示,TVT-O客观成功率、主观成功率均与TVT相似[P>0.05,OR 0.78,95%可信区间(CI):0.47~1.30;P>0.05,OR 0.93,95%CI:0.51~1.68)],TVT-O的"膀胱损伤"发生率低于TVT(P<0.01,OR 0.16,95%CI:0.05~0.49),TVT-O的"尿路症状"发生率与TVT相似(P>0.05,OR 0.90,95%CI:0.61~1.34)。因文献的异质性和结论的高敏感性,不能确定TVT-O"术后疼痛"发生率是否增高。结论:TVT-O术是一种疗效确切的无张力阴道吊带术,与TVT术的成功率、尿路症状相似而膀胱损伤的风险减少。但须进一步研究确证"术后疼痛"发生率是否增加。     

The relation between age, time since menopause, and endometrial cancer in women with postmenopausal bleeding

The objective is to assess among women with postmenopausal bleeding the relationship of age and time since menopause on one hand and the presence of endometrial cancer and atypical hyperplasia on the other hand. In a multicenter prospective cohort study, 614 women presenting with postmenopausal bleeding were included. Women underwent transvaginal sonography and, in cases where the endometrial thickness was >4 mm, endometrial sampling. Splines were used to assess the association between each of the continuous variables and (pre)malignancy of the endometrium. Subsequently, univariate and multivariate analysis were performed. The average age for women without (pre)malignancy was 61.7 years (SD 9.8). As malignant and premalignant cases were found to have similar age, these subgroups were merged in the analyses. Age was an independent predictor of (pre)malignancy. In women younger than 55 years, the odds ratio was 1.9 (95% CI: 1.1-3.3) for each year under 55 years of age and 1.03 (95% CI: 1.00-1.06) for each year over 55 years of age. The risk of (pre)malignancy of the endometrium was 4.9% in women less than 3 years postmenopausal versus 19.7% in women more than 20 years postmenopausal. However, in a multivariate analysis only age contributed to the prediction of risk. This study demonstrates that, in postmenopausal women with vaginal bleeding, the risk of (pre)malignancy of the endometrium is low in women under 50 years of age, increases considerably until 55 years of age, and rises only modestly with further advancing age. Future studies should explore whether these findings can be incorporated in the diagnostic work-up of women with postmenopausal bleeding.     

Cryotherapy as the treatment modality of postcoital bleeding: A randomised clinical trial of efficacy and safety

Background:  Postcoital bleeding is a common gynaecological problem that impacts on a woman's quality of life and sexual function. There is little systematic research into its management.
Aims:  To assess the efficacy and side-effects of cryotherapy as treatment for postcoital bleeding.
Methods:  A prospective randomised controlled trial was conducted in a tertiary referral hospital in Hong Kong. A total of 85 women who presented with postcoital bleeding were recruited, and randomised to cryotherapy or no treatment. The treatment group received cryotherapy with compressed carbon dioxide through a cryoprobe placed on the cervix, and controls had cryoprobe on the cervix without compressed carbon dioxide flow. All recruited women were followed up two weeks, three months and six months to review their symptoms and response to the treatment.
Results:  The treatment group had a significantly better long-term cure rate and improvement rate. At six months, the cryotherapy group reported a cure rate of 72.1% while that in the control group the cure rate was 50.0% ( P  = 0.04). The number needed to treat was 5. The mean improvement rate of the cryotherapy group was 82.88% ± 35.87 but was only 61.62% ± 55.30 in the control group ( P  = 0.04). The results were more significant in women with the defined pathological cervix. Apart from the vaginal discharge at second week follow up in the treatment group, there was no statistical significant difference in side-effects and complications among two groups.
Conclusion:  Our study demonstrated that cryotherapy is a safe and an effective treatment for postcoital bleeding.     

Constant estrogen, intermittent progestogen vs. continuous combined hormone replacement therapy: tolerability and effect on vasomotor symptoms.

OBJECTIVE: To compare the efficacy and tolerability of a novel oral constant estrogen plus intermittent progestogen hormone replacement therapy (HRT) regimen to a continuous combined HRT regimen in postmenopausal women. METHODS: Subjects were randomly assigned to receive treatment with either constant 17beta-estradiol (E2), 1 mg, plus intermittent norgestimate (NGM) 90 microg (3 days off, 3 days on) (n=221) or E2 2 mg/norethisterone acetate (NETA) 1 mg (n=217) for 1 year. Treatments were evaluated based on the incidence of hot flushes and uterine bleeding. RESULTS: Both regimens had similar bleeding profiles and provided comparable vasomotor symptom relief. However, breast discomfort and edema were experienced by twice as many subjects who received E2/NETA. CONCLUSIONS: The constant E2/intermittent NGM regimen was well tolerated and possesses similar efficacy compared with a continuous combined E2/NETA regimen and may be considered whenever HRT without withdrawal bleeding is deemed appropriate.