Recent and past use of conjugated estrogens in relation to adenocarcinoma of the endometrium

It has been suggested that the reported association between estrogen use and endometrial cancer may have been biased because estrogens provoke uterine bleeding in women with otherwise asymptomatic disease. To evaluate this hypothesis we compared 149 patients with endometrial cancer and 402 control subjects with other conditions with reference to the time when they had last used conjugated estrogens. In women who had last used conjugated estrogens two or more years previously and who had taken them for at least five years, the rate-ratio estimate was 3.3 (95 per cent confidence interval, 1.4 to 8.0) relative to women who had never used them. Uterine bleeding, and hence the diagnosis of otherwise asymptomatic cancer, cannot be attributed to estrogen use that ceased in the distant past. Our results suggest that such use has a residual effect on the risk of endometrial cancer; this effect is not accounted for by biased selection of cases according to estrogen use.     

Increased risk of endometrial carcinoma among users of conjugated estrogens.

The possibility that the use of conjugated estrogens increases the risk of endometrial carcinoma was investigated in patients and a twofold age-matched control series from the same population. Conjugated estrogens (principally sodium estrone sulfate) use was recorded for 57 per cent of 94 patients with endometrial carcinoma, and for 15 per cent of controls. The corresponding point estimate of the (instantaneous) risk ratio was 7.6 with a one-sided 95 per cent lower confidence limit of 4.7. The risk-ratio estimate increased with duration of exposure: from 5.6 for 1 to 4.9 years exposure to 13.9 for seven or more years. The estimated proportion of cases related to conjugated estrogens, the etiologic fraction, was 50 per cent with a one-sided 95 per cent lower confidence limit of 41 per cent. These data suggest that conjugated estrogens have an etiologic role in endometrial carcinoma.     

Sequential use of conjugated estrogens and medroxiprogesterone in the climacteric syndrome: clinical and histological findings

Seventy-four symptomatic postmenopausal women received conjugated equine estrogens, 0.625 mg daily, alternating 3 wk of treatment with 1 wk free. Medroxyprogesterone acetate, 10 mg daily, was added from day 12 to day 21 of the estrogen therapy. The length of treatment ranged between 36 and 50 mth (media 42.8).

This sequential treatment appears to be an effective medication for menopausal women as 86.4% of patients showed a complete regression of symptoms. Its acceptability may be considered good since few side effects and low incidence of abandons (12.2%) were registered.

Medroxyprogesterone seems to be a useful agent to counteract the possible cocarcinogenetic effect of conjugated estrogens on account of the high incidence of induced secretory endometrium obtained (92.2%), the reversal of six pretreatment endometrial hyperplasias and the absence of any premalignant endometrial lesion after at least 3 yr of this sequential treatment. The only case of endometrial cancer registered does not jeopardize this conclusion as was observed in a women who took medroxyprogesterone very irregularly.     

Risk of gestational hypertension and preeclampsia in women who discontinued or continued antidepressant medication use during pregnancy

Purpose

This study aimed to examine the association between discontinued and continued use of antidepressants and risk for gestational hypertension (GH) and preeclampsia (PE).

Methods

Data from the MotherToBaby pregnancy studies from 2004 to 2014 were analyzed to compare women who discontinued antidepressant use ?20 weeks of gestation (discontinuers) and women who continued antidepressant use ≥20 weeks of gestation (continuers) to non-users for risk of GH (blood pressure ≥140/90 mmHg on two or more occasions at ≥20 weeks of gestation) and PE (GH with proteinuria). Maternal data, including exposures and study outcomes, were collected through multiple phone interviews. Medical records were used to validate outcomes. Odds ratios (ORs) and 95 % confidence intervals were estimated using logistic regression. Risk for GH and PE were also assessed within antidepressant drug classes.

Results

Data from 3471 women were analyzed. Continuers were significantly at risk for GH (adjusted odds ratios (aOR) 1.83; 95 % CI 1.05, 3.21) after adjustment. Analyses by drug class showed that continued use of serotonin-norepinephrine reuptake inhibitors (SNRI) increased risk for GH; however, of the 21 women who continued to use SNRI, only 3 developed GH. Continuers who used two or more antidepressant drug classes had increased risk for PE. Selective serotonin reuptake inhibitors or other antidepressant use was not associated with increased risk for GH or PE. No significant associations with PE or GH were found for discontinuers.

Conclusions

Results suggest that women who continued to use antidepressants in the second half of pregnancy are at risk for GH and PE. No significant association was found among discontinuers.

     

Bazedoxifene/conjugated estrogens and quality of life in postmenopausal women

Objective

To assess the effects of bazedoxifene/conjugated estrogens (BZA/CE) on sleep parameters and health-related quality of life (HR-QOL).

Methods

This was a 12-week, multicenter, double-blind, placebo-controlled phase 3 study. Postmenopausal women with an intact uterus and experiencing ≥7 moderate-to-severe hot flushes daily were randomized to BZA 20 mg/CE 0.45 mg, BZA 20 mg/CE 0.625 mg, or placebo. In these secondary efficacy analyses, the Medical Outcomes Study (MOS) sleep scale and Menopause-Specific Quality of Life (MENQOL) questionnaires and the Menopause Symptoms Treatment Satisfaction Questionnaire (MS-TSQ) evaluated measures of sleep, menopausal symptoms, and satisfaction with treatment, respectively.

Results

A total of 318 subjects (mean age, 53.4 years) received ≥1 dose of study drug. At Week 12, BZA 20 mg/CE 0.45 and 0.625 mg showed significant improvements over placebo in the MOS sleep scale for time to fall asleep, sleep adequacy, sleep disturbance, and sleep problems indexes I and II (P < 0.001). A reduction in hot flush frequency was significantly associated with improvement in sleep parameters (P < 0.05) based on linear regression and responder analyses. Both BZA/CE doses showed significantly greater improvements over placebo in vasomotor function and total MENQOL score (P < 0.001). Results of the MS-TSQ showed that subjects treated with BZA/CE versus placebo reported significantly greater overall satisfaction with treatment (P < 0.05), as well as greater satisfaction with sleep quality, ability to control hot flushes during the day and night, effect on mood/emotions, and tolerability.

Conclusion

Symptomatic postmenopausal women treated with BZA/CE experienced significant improvements in sleep parameters and overall HR-QOL.     

子宫内膜癌腹水细胞学阳性的危险因素和预后意义

目的探讨子宫内膜癌患者腹水细胞学阳性的危险因素和预后意义。方法收集2005年1月1日至2010年12月31日北京协和医院收治的486例初治子宫内膜癌患者的临床资料进行回顾性分析,单因素及多因素分析腹水细胞学阳性对预后的影响。结果 1)子宫内膜癌患者中腹水细胞学检查阳性率为4.8%。2)非子宫内膜样癌(P=0.000)、FIGO分期(2009)为Ⅲ-Ⅳ期(P=0.000)、子宫深肌层受累(P=0.001)、宫颈间质浸润(P=0.018)是子宫内膜癌腹水细胞学阳性的影响因素。3)子宫内膜癌腹水细胞学阳性患者的5年无进展生存率(70.9%vs90.0%)、5年总生存率(72.2%vs 96.0%)均低于腹水细胞学阴性患者;单因素分析腹水细胞学阳性对无进展生存时间和总生存时间的影响,差异均具有统计学意义(P=0.005,P=0.000);4)多因素分析显示腹水细胞学阳性并不是无进展生存时间、总生存时间的独立危险因素(RR=3.812,95%CI 0.897~16.200,P=0.070;RR=3.426,95%CI 0.800~14.673,P=0.097)。结论子宫内膜癌的腹水细胞学阳性与非子宫内膜样的病理类型、FIGO分期(2009)、深肌层浸润、宫颈间质浸润相关。腹水细胞学阳性不是子宫内膜癌的独立预后影响因素。     

2型糖尿病与子宫内膜癌关系的回顾性分析

目的:探讨2型糖尿病对子宫内膜癌的影响.方法:回顾性分析旺旺医院2005年至2010年间25例子宫内膜癌病例资料,分析合并有糖尿病的子宫内膜癌患者在肿瘤患病率、分期、预后等方面与未合并糖尿病的患者间的差异.结果:合并糖尿病的子宫内膜癌患者诊断时更多属于Ⅲ期;合并糖尿病的子宫内膜癌患者中体质量指数多为超重,同时血糖控制不...     

Cost is a barrier to widespread use of liquid-based cytology for cervical cancer screening in Korea

This study aimed to document current cervical cancer screening practices of physicians in Korea. Questionnaires were distributed to 852 Korean obstetricians and gynecologists, who attended the 91st Conference of the Korean Society of Obstetrics and Gynecology held during May, 2005. Questionnaires were returned by 30.6% (260/852) of the recipients and 254 of these were eligible for analysis. Sixty-seven percent started cervical cancer screening women at age 20, and 65% replied that they would continue annual screening in a 35-yr-old woman with three consecutive normal cytologic tests. Over 65% of respondents preferred conventional cytologic screening to liquid-based cytology. The cost was a major determinant for selecting screening method. Fifty-three percent used the human papillomavirus DNA test as a triage for atypical squamous cells of undetermined significance. Our findings suggest that majority of Korean obstetricians and gynecologists in hospital prefer annual conventional cytologic testing to liquid-based cytology for financial reason.     

Metastases to the ovary arising from endometrial,cervical and fallopian tube cancer: recent advances

The introduction of genomic studies has enabled assessment of the clonality of synchronous tumours involving the ovary and other sites in the female genital tract in a definitive way. This has led to the abandonment of conventional approaches to primary site assignment, and the recognition that most such synchronous neoplasms are clonally related single tumours with metastatic spread, rather than independent primary tumours. These discoveries have implications for diagnostic practice, analogous to the gradual change over the last few decades in our approach to mucinous neoplasms of the ovary metastatic from the gastrointestinal tract. In this review, we first examine the routes of metastasis to the ovary, and then discuss the diagnostic and clinical implications of concurrent ovarian carcinomas arising in combination with endometrial, endocervical and tubal carcinomas. It is proposed that cases of primary low-grade endometrioid endometrial carcinoma with a secondary unilateral ovarian tumour, both with indolent characteristics, may be classified as ‘FIGO stage IIIA-simulating independent primary tumours’, with a comment that conservative management would be appropriate. It should be recognised that human papillomavirus-associated endocervical adenocarcinomas may result in synchronous or metachronous ovarian metastases that appear to be unrelated to the primary tumour, and that these may be managed conservatively in the absence of other sites of disease. In cases of tubo-ovarian high-grade serous carcinoma, tubal intraepithelial or contralateral adnexal involvement should count as a pelvic disease site for staging purposes.     

Androgens and estrogens in relation to hot flushes during the menopausal transition.

In this paper, the association of hormones to vasomotor complaints during the menopausal transition is discussed. Fifty-seven regularly menstruating women without history of hormone replacement therapy (HRT) were selected for a longitudinal, prospective study around the menopausal transition. The mean age at the start of the study was 51.3 (+/-2.0) years. At intervals of 12 months all women went through a semi-structured interview and filled in questionnaires. Venous blood samples were collected every 12-month for analyses of estradiol (E2), testosterone, androstendione, dehydroepiandrosterone-sulphate (DHEA-S), follicle stimulating hormone (FSH), thyrotropin (TSH), and luteinizing hormone (LH). Vasomotor complaints were tested using questions about hot flushes and bouts of sweating in terms of occurrence, frequency and degree of distress. Forty-six percent of the subjects reported hot flushes and bouts of sweating before menopause, increasing to 67% during the first year after menopause and 49% in the second year postmenopause. Low levels of estradiol and high levels of FSH were associated with vasomotor complaints before menopause. During menopause high levels of TSH were related to vasomotor complaints. The first year after menopause, women, who at this point achieved hot flushes, were characterised by high levels of E2, but declining and low levels of FSH, but increasing. Postmenopausal, high levels of testosterone and DHEA-S seemed to protect against vasomotor symptoms. Our most important finding was, that among women who achieved hot flushes at the first assessment postmenopause, the high androgen levels was a significant predictor of recovery from hot flushes at the last assessment, 1 year later.     

Tibolone versus conjugated estrogens and sequential progestogen in the treatment of climacteric complaints

Objective: Tibolone has been shown to alleviate climacteric symptoms. This study was designed to compare the effect of tibolone (Livial®, 2.5 mg daily) on different climacteric complaints and its impact on the endometrium, determined by vaginal ultrasound, with that of conjugated estrogens (Premarin®, 0.625 mg daily) continuously for 6 months in combination with the progestogen medrogestone (Colpron®, 2 × 5 mg daily for 12 days each month). Methods: One hundred and twenty-nine postmenopausal women were recruited and the severity of climacteric symptoms as well as endometrial thickness were recorded at the pre-trial examination and after 1, 3, and 6 months. Results: With the exception of vertigo, mood depression, mood disorder, loss of libido, and dryness of skin, where tibolone was found to be more effective than conjugated estrogens/medrogestone, climacteric symptoms improved significantly in both groups over the 6-month study period. Endometrial thickness did not increase significantly in the tibolone group, whereas in the conjugated estrogens/medrogestone group there was a highly significant increase after 1 month and still a trend towards significance after 6 months. Recurrence of vaginal bleeding occurred significantly less frequently in the tibolone group than in the comparison group. Conclusion: Tibolone seems to offer a complete treatment of the climacteric complaints whilst avoiding some of the problems associated with classical hormone replacement therapy.     

The effect of conjugated equine estrogens on ovariectomy-induced osteopenia in the rat

The effect of estrogen replacement on ovariectomy-induced bone loss was evaluated in mature Sprague-Dawley rats. Undecalcified tibia of ovariectomized rats were processed for quantitative histologic assessment of cancellous bone in longitudinal sections from the primary and secondary spongiosa of the proximal metaphysis. Bone content in tissue specimens was quantified as the parameter B. Ar, two-dimensional bone mineral area. Estrogen, supplied as orally administered conjugated equine estrogens, prevented bone loss through 6 weeks of treatment. The effect of conjugated equine estrogens was dose-dependent, with significant protection against bone loss observed at doses of 10 g/kg/day and higher.     

Histopathology of breast cancer in young women in relation to use of oral contraceptives.

A detailed review was made of the histopathology of 227 tumours taken from 261 women under 45 years of age with breast cancer. The tumours were classified as follows: whether oral contraceptives had been used at any time; and whether oral contraceptives had been used before first term pregnancy. All analyses were adjusted for the effects of age. Overall, 201 (88.5%) of tumours were infiltrating ductal in type, 19 (8.4%) were infiltrating lobular, and seven (3.1%) were in situ ductal. Of the infiltrating ductal tumours, 28 (14%) were grade I 88 (44%) grade II, and 84 (42%) grade III. Various other tumour characteristics were also examined (per cent of carcinoma in situ, lymphatic permeation, necrosis, lymphoplasmocytic reaction and tumour edge). None of the histopathological features assessed showed any significant association with oral contraceptive use. Some characteristics of the areas of breast tissue adjacent to the tumours were also studied. The degree of cyst formation was considerably less pronounced in those using oral contraceptives before first term pregnancy than in those not doing so.     

The effect of low-dose conjugated equine estrogens and cyclic MPA on bone density

OBJECTIVE: to compare the effect of 0.3 and 0.625 mg conjugated equine estrogens on bone mineral density (BMD) in a private practice setting. METHODS: postmenopausal women interested in hormone replacement therapy were prescribed either 0.3 or 0.625 mg conjugated equine estrogens daily with 10 mg medroxyprogesterone acetate days 1-12 of the month. All women were given calcium citrate 1000 mg/day and vitamin D 400 IU/day. DEXA bone mineral density studies of the spine and hip were performed at baseline and 1 year. RESULTS: there was no significant difference in BMD at the spine, the trochanter or the femoral neck compared with baseline in either the 0.625 or 0.3 mg group. The mean percent increase in BMD for the 0.3 versus 0.625 mg group was: spine 2.6 versus 3.8%, femoral neck 1.8 versus 1.5%, and trochanter 0.5 versus 2.6%. CONCLUSION: both the 0.625 mg dose and the 0.3 mg dose of conjugated equine estrogens preserved BMD at the spine and hip over one year in early postmenopausal women who were also given cyclic medroxyprogesterone acetate, calcium citrate and vitamin D.     

Comparative effect of estriol and equine conjugated estrogens on the uterus and the vagina

Estriol has been reported to act selectively on the vagina and cervix without causing endometrial proliferations. Studies comparing this effect of estriol to that of equine conjugated estrogens after intravaginal administration have not been reported. In this study, intravaginally administered Ortho- Gynest which contains estriol, and Premarin which contains equine conjugated estrogens, were evaluated for their ability to stimulate vaginal maturation and uterine growth in rats. Approximately 15 times more conjugated estrogens than estriol was needed to induce the same degree of vaginal cornification in castrated rats. In contrast, estriol was less potent than the conjugated estrogens in causing uterine growth in immature rats after subcutaneous administration in sesame oil and in mature rats after intravaginal administration in cream preparations. In studies evaluating the vaginal irritation potential of estriol vaginal cream, the irritation exhibited by treated rabbits was found to be comparable to that of sham-treated control rabbits. Estriol was well-tolerated in an oral acute safety study in rats.