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PubMedDate not supplied

High-resolution MR imaging of the vagina.

High-resolution magnetic resonance (MR) imaging with pelvic phased-array and endoluminal coils provides information on vaginal abnormalities heretofore not available with other imaging modalities. Congenital anomalies of the vagina can result from disorders of lateral fusion of the descending müllerian ducts and ascending urogenital sinus, developmental absence of the müllerian ducts, or disorders of vertical fusion. In these conditions, MR imaging can depict the presence or absence of the vagina, cervix, and uterus and help determine whether these structures contain a septum or are duplicated or distended with blood. Gartner duct cysts and Bartholin gland cysts have the same signal intensity characteristics, but the former are located in the anterolateral aspect of the proximal third of the vagina and the latter are in the posterolateral portion of the lower vagina. Entero-, vesico-, and ureterovaginal fistulas result from obstetric and surgical trauma, radiation therapy, or inflammatory bowel disease. MR imaging has great potential for detection and characterization of these fistulas. MR imaging can be used to detect and stage primary and secondary vaginal tumors. However, neither signal intensity nor patterns of enhancement enable confident prediction of the histologic subtype of vaginal malignancy.

Adult↗
PubMed1999

Clinical evaluation of follow-up methods and results of atypical glandular cells of undetermined significance (AGUS) detected on cervicovaginal Pap smears.

OBJECTIVES: The aim of this study was to evaluate the efficacy of the follow-up methods and results of atypical glandular cells of undetermined significance (AGUS) detected on cervicovaginal Pap smears. METHODS: From May 1991 to December 1996, we have performed 407, 451 cervicovaginal Pap smears, of which 326 patients were identified as AGUS. Of the 326 patients, 268 patients were followed by repeat Pap smears, colposcopy, cone biopsy, or endometrial curettage. RESULTS: The incidence of AGUS on Pap smears is approximately 0.08%. The mean age of the patients was 43 years (range 22-79 years). The most common complaint was abnormal vaginal bleeding. The gross findings of the cervix were normal to mild erosion. The following past histories of patients could affect the AGUS results on Pap smear: 30 had cone biopsy, 21 had Pap smears on pregnancy and within 8 weeks after delivery or evacuation, 3 were on hormonal replacement therapy, 2 had intrauterine devices for contraception, and 5 were undergoing follow-up after treatment of cervical cancer. The benign lesions detected during follow-up periods were 6 microglandular hyperplasia of the cervix, 5 atypical squamous metaplasia of the cervix, 2 cervical endometriosis, 2 tubal metaplasia, 10 cervical myoma, 11 cervical polyps, 9 endometrial polyps, 3 uterine myoma, 1 pelvic endometriosis, 1 ovarian endometriosis, and 4 uterine adenomyosis. The premalignant or malignant lesions of the cervix were 4 low-grade squamous intraepithelial lesions, 24 high-grade squamous intraepithelial lesions, 8 glandular atypia/dysplasia, 5 adenocarcinoma in situ, 3 microinvasive adenocarcinoma, and 4 invasive adenocarcinoma. The neoplastic lesions of the uterus were 6 endometrial hyperplasia, 11 endometrial adenocarcinoma, 1 malignant mixed Müllerian tumor, and 1 metastatic endometrial adenocarcinoma. Sixty-seven (25%) of 268 patients followed up were identified as having clinically significant lesions of the cervix or uterus. The detection rates of abnormal lesions were 3.1% with repeated Pap smears (3/98), 28.4% with colposcopic-directed biopsy (31/109), 63.6% with cone biopsy (35/55), and 29.7% with endometrial curettage (19/64). CONCLUSION: AGUS on Pap smears showed various benign and malignant lesions of the cervix or uterus. The clinicians must communicate with the pathologists regarding the patient's clinical information as well as the origin of the atypical glandular cells in Pap smears. We recommend that patients with AGUS on Pap smear should undergo immediate intensive diagnostic studies, including colposcopic-directed biopsy with endocervical curettage or cone biopsy, to detect cervical lesions and endometrial curettage to detect endometrial lesions.

Adult↗
PubMed1995

Vulvar and vaginal colposcopic pictures of human papillomavirus infection.

The recognition of both overt and subclinical vulvar HPV infection has become increasingly important. However, although molecular biological evidence has indicated a strong link between HPVs and cancer, clinical or epidemiological evidence is still not fully convincing. We studied 159 HPV DNA positive patients, using a dot blot hybridization technique (ViraPap and ViraType, Digene Diagnostics. USA), and 69 randomly selected HPV negative controls drawn from the same clinical setting, at the outpatient clinic, Department of Obstetrics and Gynecology, University Central Hospital, Helsinki, Finland. Seven patients had HPV 6/11, 51 had HPV 16/18, 52 had HPV 31/33/35 25 had more than one of the three HPV DNA groups ("mixed"), and 24 had untypable HPV DNA. Cases and controls were examined at four month intervals. The mean follow-up time was 12.2 months (SD 8.7) for the cases, and 12.8 (SD 6.9) for the controls. Although vulvar or vaginal abnormalities (acetowhite epithelium, squamous papillomatosis, filaments, satellite lesions, fissure, papules, or exophytic condylomas) were more commonly seen in the cases than in the controls, the difference was significant only for exophytic condylomas. In conclusion, colposcopy is not a good predictor of HPV infection and should not be used as an HPV screening test. HPV DNA hybrodization did not help more than the histopathologic findings in the diagnosis, but allowed the recognition of high-risk patients. The role of an accurate colposcopic examination with target biopsies remains essential.

Adult↗
PubMed2005

Primary cervical lymphoma: report of two cases and review of the literature.

BACKGROUND: Primary lymphoma arising from the female genital tract has been rarely encountered. Primary cervical lymphoma is even rarer in gynecologic oncology practice and accounts for approximately only 1% of extranodal lymphomas. In this article, two cases of cervical lymphoma are presented with a review of the available literature. CASE HISTORIES: A 51-year-old woman presented with abnormal vaginal discharge. On pelvic examination, cervix was apparently normal; however, a solid and mobile pelvic mass was palpated. Pap smear was reported as HSIL at another institution. Radiological evaluation revealed a cervical mass with a 3 cm diameter. Histopathological evaluation of LEEP material was reported as diffuse large B cell lymphoma. We performed abdominal hysterectomy plus bilateral salphingo-oopherectomy and the patient was treated with adjuvant 6 cycles of CHOP chemotherapy. A second case was a 49-year-old postmenopausal woman who had undergone a routine gynecologic follow-up examination without any complaint at another institution. Routine cytological smear revealed HSIL. Punch biopsy under colposcopic examination presented no remarkable pathology except for a benign inflammation. Due to discordance between cytology and histology, LEEP was performed under colposcopic examination, which revealed follicular lymphoma grade III. This patient was treated with 6 cycles CHOP chemotherapy without any surgery. CONCLUSION: Primary cervical lymphoma is a rare disorder. Although most reported cases in the literature have a normal Pap smear, some may represent with co-existent cytological abnormalities. Therefore, cervical lymphomas should be kept in mind in patients with cytological abnormalities.

Female↗
PubMed2002

Endometrial-type cells in cervico-vaginal smears: clinical significance and cytopathologic correlates.

This study assessed the significance of endometrial-type cells (ETC) in cervico-vaginal (CV) smears in patients 45 yr and older by evaluating quantitatively and qualitatively the relationship of ETC to subsequent endometrial pathology. In a 3-yr period (1997-1999) at the Johns Hopkins Cytopathology Laboratory, 1,162 CV smears with ETC were found in patients 45 yr and older. In all cases with positive follow-up by tissue biopsy/resection, i.e., endometrial hyperplasia (EHP) and endometrial adenocarcinoma (EACA), the CV smears were reevaluated and compared to the control group (i.e., patients with normal endometrial biopsies). The following cytologic characteristics were recorded: quantity of ETC, type of ETC (epithelial, stromal/histiocyte-type, or mixed), cellular atypism, presence of inflammation, smear background, and associated estrogen effect. Of the 1,162 patients with ETC, 432 cases (37%) had tissue follow-up as follows: EACA, 18 (4.2%); EHP, 20 (4.6%); leiomyomata, 17 (3.9%); endometrial polyp, 21 (4.9%); benign/within normal limits (WNL), 339 (78.5%); nondiagnostic, 17 (3.9%). Cytologic characteristics of ETC showed subtle but definite quantitative and qualitative differences in the major pathologic groups examined. All instances of cancers and hyperplasia occurred in postmenopausal (PM) women. Abnormal vaginal bleeding was the presenting complaint in 66.7% of EACA, 45% of EHP, and 28.6% of benign endometrium. ETC in PM CV smears are associated with significant endometrial lesions (carcinoma, hyperplasia) in less than 9% of the patients. It is concluded that the distinction between EACA and EHP can be difficult. The presence of a large number of ETC, predominantly of epithelial or a mixed (epithelial and stromal) type, is more often associated with EACA or EHP than with benign endometrium. The presence of cytologic atypia and/or diathesis is additionally helpful for the diagnosis of EACA.

Adenocarcinoma↗
PubMed2000

Alpha-fetoprotein producing uterine corpus carcinoma: A hepatoid adenocarcinoma of the endometrium.

A case of alpha-fetoprotein (AFP) producing endometrial carcinoma in a 60-year-old Japanese woman is presented. The patient complained of abnormal vaginal bleeding of 10 days' duration. On admission a uterine corpus mass and high serum AFP concentration (31950 ng/mL) was noted. There was no tumorous lesion in any other organ radiographically and endoscopically. Histologically, the biopsy specimen taken from the uterine mass showed a poorly differentiated endometrial carcinoma and a radical hysterectomy was subsequently performed. The postoperative serum AFP value transiently decreased with chemotherapy, however, lung metastases were found and the patient died 12 months following surgery. The resected uterus had a necrotic tumor, 6 x 5 x 4 cm in size, filling the endometrial cavity, characterized by exophytic growth with infiltration in the myometrium. Histologically, the tumor was composed of the main medullary carcinoma area with microcysts and admixed small areas of well-differentiated endometrioid adenocarcinoma, accompanied by a smooth transition with one another. In both the areas, the tumor cells had immunoreactive AFP, alpha-1-antitripsin, albumin, transferrin, carcinoembryonic antigen, CA19-9, and epithelial membrane antigen. There was no histologic evidence for a germ cell tumor. Based on these findings, this uterine corpus tumor was regarded as hepatoid variant of endometrial carcinoma. Although the histogenesis remains controversial, we assume the hypothesis that the tumor may arise in the endometrium per se in association with abnormal differentiation of muellerian duct elements.

Adenocarcinoma↗
PubMed1981

Statutes of limitations: the special problem of DES suits.

In 1971, medical studies determined that DES causes a rare type of vaginal cancer in a small number of daughters of mothers who took DES during pregnancy. Subsequently, medical studies determined that exposure to DES can cause other vaginal abnormalities in the daughters, some of which may be precancerous. As a result of these discoveries, many lawsuits have been filed by these daughters against DES manufacturers. Many DES suits may be barred by statutes of limitations, both because the number of years between the daughters' exposure to DES in utero and the discovery that DES can cause injuries exceeds the statutory period, and because the cancer or other injuries caused by DES may not develop for many additional years. This Note discusses two methods that DES plaintiffs may be able to use to overcome the potential statutes of limitations bar: the discovery rule, and state provisions which toll the statute of limitations for minors. The Note contends that courts should apply an expanded discovery rule to DES suits to avoid the unfair result of barring a claim before the plaintiff could have known that she had a cause of action. In addition, the Note argues that the injury which causes the statute of limitations to begin to run in DES suits should not be rigidly defined. Finally, the Note urges that courts allow eligible DES plaintiffs to take advantage of applicable state provisions that toll the statute of limitations for minors.

Adenocarcinoma↗
PubMed1978

Contraception.

Explore the source record for details and available documents.

Adolescent↗
PubMedDate not supplied

Endometrial carcinoma presenting as hematometra mimicking a large pelvic cyst.

Large pelvic cysts are commonly seen in gynecologic practice; their heterogeneous origin is reflected in their pleomorphic clinical features. We report the case of a 64-year-old multiparous postmenopausal woman with an unusual manifestation of endometrial adenocarcinoma that presented as hematometra mimicking a large pelvic cyst. In this case, hematometra was well demonstrated by transabdominal sonography, but transvaginal sonography allowed better visualization of the endometrial lining and suggested the correct diagnosis of endometrial cancer. Abnormal vaginal bleeding or hematometra in postmenopausal women should lead to assessment of the endometrial mucosa. Transvaginal sonography can be used to visualize neoplastic lesions in the endometrium when hematometra is detected through transabdominal sonography.

Adenocarcinoma↗
PubMed1996

Endometrial metaplasia as a source of atypical glandular cells in cervicovaginal smears.

Cytohistological correlation of abnormal cervicovaginal smears indicates that endometrial metaplasia may be associated with the presence of atypical glandular cells. Seven patients with histologically confirmed endometrial metaplasia had atypical glandular cells in cervicovaginal smears; five smears were interpreted as being suspicious for endometrial adenocarcinoma. Most of the patients (5/7) were postmenopausal (mean age = 61.3 years), and three of seven patients had abnormal vaginal bleeding. The corresponding endometrial tissue specimens demonstrated various combinations of eosinophilic, papillary, squamous, and tubal metaplasia; in one case tubal metaplasia occurred in association with an endometrial polyp. Cytologic features noted in the cervicovaginal smears from all seven patients were similar and included small clusters of atypical glandular cells in an inflammatory background. Intracytoplasmic vacuoles were often present, and a moderate degree of aniosonucleosis was noted. Enlarged glandular nuclei contained finely granular chromatin and distinct nucleoli. The differential diagnosis of atypical glandular cells includes endometrial hyperplasia and well-differentiated endometrial adenocarcinoma. The atypical cells associated with endometrial metaplasia were characterized by a relatively low N:C ratio and evenly distributed chromatin. In contrast, the cells of endometrial carcinoma typically demonstrate increased N:C ratios and irregularly distributed chromatin.

Adenocarcinoma↗
PubMed2000

Cytology of polypoid adenomyomas: a report of two cases.

Uterine polypoid adenomyomas, both typical and atypical variants, often arise in the lower uterine segment or endocervical canal as pedunculated polypoid masses that may be accessible for cytologic sampling. However, their cytologic findings have rarely been described in the literature. Two women in their reproductive age presented with abnormal vaginal bleeding. The cervicovaginal smear of the first patient contained sheets and strips of reactive endocervical cells in an inflammatory background. In addition, loose aggregates of spindle-shaped smooth muscle cells were also noted. The findings were consistent with those of a typical polypoid adenomyoma. The cervicovaginal smears of the second patient consisted of tightly packed, crowded clusters of glandular cells which were initially interpreted as atypical glandular cells, suspicious of adenocarcinoma. In retrospect, loose aggregates of smooth muscle stromal cells were noted. Subsequent curettage revealed an atypical polypoid adenomyoma. The cytologic findings of typical polypoid adenomyoma were nonspecific except for the presence of loose aggregates of smooth muscle cells. The cytologic features of an atypical polypoid adenomyoma may mimic that of a neoplastic glandular process. The findings of tightly packed clusters of glandular cells and loose aggregate of bland-appearing smooth muscle cells in premenopausal patients may suggest the diagnosis of atypical polypoid adenomyoma. Diagn. Cytopathol. 2000;22:176-180.

Adenomatous Polyps↗
PubMed1999

Puerperal and intrapartum group A streptococcal infection.

OBJECTIVE: To determine the demographic and clinical variables characteristic of non-epidemic intrapartum or puerperal group A streptococcal (GAS) infection. METHODS: The records of 47 patients diagnosed with intrapartum or puerperal GAS infection over a 6 1/2 year period at Hadassah-University Hospital-Mt. Scopus, Jerusalem were reviewed. Data regarding 25,811 women, the general population of women that delivered during that period, were obtained from their computerized medical records. Frequency distributions, t-test, chi-square, and Spearman's Rank Correlation were used, as appropriate, to analyze and compare demographic and clinical variables associated with development of GAS infection, its clinical course and subsequent development of septic shock. RESULTS: Mean age of mothers with GAS infection was higher than that of our general pregnant population (30.4 versus 27.4 years, P = 0.0019), and a higher proportion of GAS infected patients (30% versus 12%, P < 0.005) experienced PROM. Thirty-one (66%) women had fever as their sole presenting symptom, eight (17%) had fever and abdominal pain, seven (15%) had fever and abnormal vaginal bleeding, and one patient (2%) presented with a rash. Three patients (6%) developed a septic shock. Two of these patients presented with symptoms more than 14 days after delivery. CONCLUSIONS: We describe the characteristics of non-epidemic intrapartum or puerperal GAS infection. Data from our study and review of the literature suggest that some patients who develop septic shock may present later in the puerperium than patients with an uncomplicated GAS infection.

Abdominal Pain↗
PubMed1988

Breast cancer metastasizing to the uterine cervix.

Three cases of breast cancer that metastasized to the uterine cervix are presented. A review of the literature disclosed 21 additional cases. Seventy-five percent of the patients presented with abnormal vaginal bleeding, 62% had no gross evidence of malignancy on examination, and in 89% the cervical metastases were a manifestation of widespread disease.

Adult↗
PubMed1990

Adenocarcinoma of the uterine cervix.

In Finland, the incidence of cervical cancer has shown a decreasing tendency since the 1960s. The same trend, however, has not been noticed in the incidence of cervical adenocarcinoma. The reason for this is not known, although many studies have shown differences in the cause, epidemiology, and biology of the epidermoid and adenocarcinoma of the uterine cervix. A total of 106 new patients with cervical adenocarcinoma were treated at our institution from 1976 to 1980, which represents 20.4% of all cervical carcinomas treated. The mean age of the patients was 58.1 years (range, 29 to 82 years) and the peak incidence was in the group 60 to 69 years of age. Most of the patients were postmenopausal (71.7%) and the main symptom was abnormal vaginal bleeding (78.3%). The proportion of Stage I was 61.3%. Combined operative and radiation therapy was used in 74.5% of the patients. The overall 5-year survival rate was 65.1% (corrected 74.5%), which did not differ from that of patients with squamous cell carcinoma. The most significant prognostic factors were the size of the tumor, presence of pelvic lymph node metastases, and the stage of the disease.

Adenocarcinoma↗
PubMed1991

Stage IE primary malignant lymphomas of the uterine cervix.

The experience of the authors with primary non-Hodgkin's lymphoma of the uterine cervix from 1980 to 1986 included five Ann Arbor Stage IE cases successfully managed by meticulous staging and radiation therapy. The clinicopathologic features of the patients are described and compared with 38 previously reported Stage IE cases. When all 43 patients were evaluated, the median age was 40 years of age (range, 20 to 80 years of age) and 77% were premenopausal. Most patients (74%) reported abnormal vaginal bleeding, although approximately 20% were asymptomatic. The primary cervical tumors were typically of large size, with half exceeding 4 cm in diameter. Using the International Federation of Gynecology and Obstetrics (FIGO) system for staging cervical cancer, stage distribution was 44% Stage I, 42% Stage II, 12% Stage III, and 2% Stage IV. Histologically, approximately 70% were of the diffuse, large cell type (Working Formulation). External beam radiation therapy supplemented by brachytherapy or hysterectomy was used for 76% of the patients reviewed. There was only one treatment failure among the 28 patients whose treatment included radiation and whose cases were followed for at least 2 years. This experience and a review of the literature indicate that most cases of primary lymphoma of the uterine cervix are Ann Arbor Stage IE, and can be cured with traditional combinations of surgery and radiation therapy after careful evaluation.

Aged↗
PubMed2000

Hormone replacement therapy in postmenopausal women: endometrial hyperplasia and irregular bleeding.

BACKGROUND: The decline in circulating oestrogen around the time of the menopause often induces unacceptable symptoms that affect the health and well being of women. Hormone replacement therapy (both unopposed oestrogen and oestrogen and progestogen combinations) is an effective treatment for these symptoms. In women with an intact uterus, unopposed oestrogen may induce endometrial stimulation and increase the risk of endometrial hyperplasia and carcinoma. The addition of progestogen reduces this risk but may cause unacceptable symptoms, bleeding and spotting which can affect adherence to therapy. OBJECTIVES: The objective of this review is to assess which hormone replacement therapy regimens provide effective protection against the development of endometrial hyperplasia and/or carcinoma with a low rate of abnormal vaginal bleeding. SEARCH STRATEGY: Electronic searches for relevant randomised controlled trials of the Cochrane Menstrual Disorders and Subfertility Group Register of Trials, MEDLINE, EMBASE, PsychLIT, Current Contents, Biological Abstracts, Social Sciences Index and CINAHL were performed. Attempts were also made to identify trials from citation lists of review articles and drug companies were contacted for unpublished data. In most cases, the corresponding author of each included trial was contacted for additional information. SELECTION CRITERIA: The inclusion criteria were randomised comparisons of unopposed oestrogen therapy, combined continuous oestrogen-progestogen therapy and sequential oestrogen-progestogen therapy with each other and placebo administered over a minimum treatment period of six months. Trials had to assess which regimen was the most protective against the development of endometrial hyperplasia/carcinoma and/or caused the lowest rate of irregular bleeding. DATA COLLECTION AND ANALYSIS: Twenty three RCTs were identified and five were excluded. The reviewers assessed the eighteen included studies for quality, extracted the data independently and odds ratios for dichotomous outcomes were estimated. Outcomes analysed included frequency of endometrial hyperplasia or carcinoma, frequency of irregular bleeding and unscheduled biopsies or dilation and curettage, and adherence to therapy. MAIN RESULTS: Unopposed moderate or high dose oestrogen therapy was associated with a significant increase in rates of endometrial hyperplasia with increasing rates at longer duration of treatment and follow up. Odds ratios ranged from 5.4 (1. 4-20.9) for 6 months of treatment to 16.0 (9.3-27.5) for 36 months of treatment with moderate dose oestrogen (in the PEPI trial, 62% of those who took moderate dose oestrogen had some form of hyperplasia at 36 months compared to 2% of those who took placebo). Irregular bleeding and non adherence to treatment were also significantly more likely under these unopposed oestrogen regimens with greater effects with higher dose therapy. There was no evidence of increased hyperplasia rates, however, with low dose oestrogen. The addition of progestogens, either in continuous combined or sequential regimens, helped to prevent the development of endometrial hyperplasia and improved adherence to therapy (odds ratios of 3.7 for sequential therapy and 6.0 for continuous therapy). Irregular bleeding, however, was more likely under a continuous than a sequential oestrogen-progestogen regimen (OR = 2.3, 95% CI 2.1-2.5) but at longer duration of treatment, continuous therapy was more protective than sequential therapy in preventing endometrial hyperplasia (OR = 0.3, 95% CI 0.1-0.97). There was evidence of a higher incidence of hyperplasia under long cycle sequential therapy (progestogen given every 3 months) compared to monthly sequential therapy (progestogen given every month). No increase in endometrial cancer was seen in any of the treatment groups during the limited duration (maximum of 3 years) of these trials. (ABSTRACT TRUNCATED)

Endometrial Hyperplasia↗
PubMed2004

Hormone replacement therapy in postmenopausal women: endometrial hyperplasia and irregular bleeding.

BACKGROUND: The decline in circulating oestrogen around the time of the menopause often induces unacceptable symptoms that affect the health and well being of women. Hormone replacement therapy (both unopposed oestrogen and oestrogen and progestogen combinations) is an effective treatment for these symptoms. In women with an intact uterus, unopposed oestrogen may induce endometrial stimulation and increase the risk of endometrial hyperplasia and carcinoma. The addition of progestogen reduces this risk but may cause unacceptable symptoms, bleeding and spotting which can affect adherence to therapy. OBJECTIVES: The objective of this review is to assess which hormone replacement therapy regimens provide effective protection against the development of endometrial hyperplasia and/or carcinoma with a low rate of abnormal vaginal bleeding. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group trials register (searched January 2003), The Cochrane Library (Issue 2, 2003), MEDLINE (1966 to January 2003), EMBASE (1980 to January 2003), Current Contents (1993 to January 2003), Biological Abstracts (1969 to 2002), Social Sciences Index (1980 to January 2003), PsycINFO (1972 to February 2003) and CINAHL (1982 to January 2003). The search strategy was developed by the Cochrane Menstrual Disorder and Subfertility Group. Attempts were also made to identify trials from citation lists of review articles and drug companies were contacted for unpublished data. In most cases, the corresponding author of each included trial was contacted for additional information. SELECTION CRITERIA: The inclusion criteria were randomised comparisons of unopposed oestrogen therapy, combined continuous oestrogen-progestogen therapy and sequential oestrogen-progestogen therapy with each other and placebo administered over a minimum treatment period of six months. Trials had to assess which regimen was the most protective against the development of endometrial hyperplasia/carcinoma and/or caused the lowest rate of irregular bleeding. DATA COLLECTION AND ANALYSIS: Sixty RCTs were identified. Of these 23 were excluded and seven remain awaiting assessment. The reviewers assessed the thirty included studies for quality, extracted the data independently and odds ratios for dichotomous outcomes were estimated. Outcomes analysed included frequency of endometrial hyperplasia or carcinoma, frequency of irregular bleeding and unscheduled biopsies or dilation and curettage, and adherence to therapy. MAIN RESULTS: Unopposed moderate or high dose oestrogen therapy when compared to placebo was associated with a significant increase in rates of endometrial hyperplasia with increasing rates at longer duration of treatment and follow up. Odds ratios ranged from (1 RCT; OR 5.4, 95% CI 1.4 to 20.9) for 6 months of treatment to (4 RCTs; OR 9.6, 95% CI 5.9 to 15.5) for 24 months treatment and (1 RCT; OR 15.0, 95% CI 9.3 to 27.5) for 36 months of treatment with moderate dose oestrogen (in the PEPI trial, 62% of those who took moderate dose oestrogen had some form of hyperplasia at 36 months compared to 2% of those who took placebo). Irregular bleeding and non adherence to treatment were also significantly more likely under these unopposed oestrogen regimens that increased bleeding with higher dose therapy. Although not statistically significant, there was a 3% incidence (2 RCTs) of hyperplasia in women who took low dose oestrogen compared to no incidence of hyperplasia in the placebo group. The addition of progestogens, either in continuous combined or sequential regimens, helped to reduce the risk of endometrial hyperplasia and improved adherence to therapy. At longer duration of treatment, continuous therapy was more effective than sequential therapy in reducing the risk of endometrial hyperplasia. There was evidence of a higher incidence of hyperplasia under long cycle sequential therapy (progestogen given every three months) compared to monthly sequential therapy (progestogen given every month). No increase in endometrial cancer was seen in any of t in any of the treatment groups during the duration (maximum of six years) of these trials. During the first year of therapy irregular bleeding and spotting was more likely in continuous combined therapy than sequential therapy. However, during the second year of therapy bleeding and spotting was more likely under sequential regimens. REVIEWERS' CONCLUSIONS: There is strong and consistent evidence in this review that unopposed oestrogen therapy, at moderate and high doses, is associated with increased rates of endometrial hyperplasia, irregular bleeding and consequent non adherence to therapy. The addition of oral progestogens administered either sequentially or continuously is associated with reduced rates of hyperplasia and improved adherence to therapy. Irregular bleeding is less likely under sequential than continuous therapy during the first year of therapy but there is a suggestion that continuous therapy over long duration is more protective than sequential therapy in the prevention of endometrial hyperplasia. Hyperplasia is more likely when progestogen is given every three months in a sequential regimen compared to a monthly progestogen sequential regimen.

Endometrial Hyperplasia↗
PubMed1976

The exfoliating cervico-vaginal surface. II. Scanning electron microscopical studies during the estrous cycle in mice.

The exfoliating epithelial surface of the ectocervix (pars vaginalis) and the vagina from normal mice was studied by scanning electron microscopy during the four main phases of the ovulatory cycle, and after estrogen administration. At proestrus, the epithelial surface usually presented cobblestone-like structure furnished with thin microvilli; at estrus, large, flat mosaics covered by long, convoluted microrugae; at metestrus, the presenting cellular surfaces were of intermediate size (i.e., between cobblestone and mosaics) having fragmented microrugae; and at diestrus, by mosaics or intermediate structures covered by microvilli. Estrogen administration to intact and oophorectomized animals resulted in flat mosaics and large numbers of loosely attached cells with rolled-up borders which permitted the observation of the basal surface of the cells. In those animals the apical aspect of the cells which lined the lumen showed convoluted microrugae with circular configuration, while the basal aspect of such cells had club-tipped microvilli. The findings were correlated with post-scanning histological examination in all animals.

Animals↗