Endometrial Mucosa Research Articles

Hysteroscopic findings in women at risk of HNPCC. Results of a prospective observational study

To report the feasibility and results of diagnostic hysteroscopy in women at risk of HNPCC. Fifty-seven women with mismatch repair gene mutations (n = 11) or Amsterdam II criteria (n = 46) were followed-up prospectively from January 1999 to March 2005. Flexible hysteroscopy was performed once a year. The endometrium was sampled routinely. Of 91 attempted hysteroscopies, 10 failed. The endometrial mucosa appeared normal in 34 cases. Polyps were seen in 12 cases, atrophy in 11, hypertrophy in 10, and fibroids in 7; two hysteroscopies suspected malignancy. A micropolypoid appearance was visualized during five hysteroscopies (5/81, 6%). Of the 86 endometrial biopsy attempts, 64 were successful and showed atrophy (n = 14), proliferation (n = 12), secretion (n = 27), polyps (n = 6), simple hyperplasia without atypia (n = 3), or cancer (n = 2). Micropolypoid appearance was not associated with a specific histological pattern. Operative hysteroscopy was done in 24 cases; in two patients with apparently benign focal lesions the results showed simple hyperplasia without atypias. Five patients underwent hysterectomy (simple hyperplasia without atypias, n = 2; endometrioid adenocarcinoma, n = 2; or secretory mucosa, n = 1). This study led to diagnosis of endometrial simple hyperplasia in 6% of cases and of cancer in 3%. In patients at risk of HNPCC, hysteroscopy appears feasible to screen endometrial pathology. Two cancers have been diagnosed over 91 patient-years at risk. Hysteroscopy should be compared to sonography as a screening tool in women at risk of HNPCC.

Female genital tuberculosis: A disease seen again in Europe

Dramatic worsening of epidemiological situation with tuberculosis (TB) in the world has made extra-pulmonary tuberculosis actual again. Female genital TB is very rare, but each case still remains a serious medical problem. A 23-year-old human immunodeficiency virus (HIV) seronegative woman with two-month duration amenorrhea underwent surgery due to lower abdominal mass simulating a left ovary carcinoma, suggested by ultrasound examinations. During sampling, we found a mass of round, up to 3 mm, necrotizing nodules, diffuse in the uterus, ovarian and tubarial surfaces, in cervical and endometrial mucosa, and even in myometrium and fat omental tissue. No tumor mass was found. Microscopically, the tissue samples from all reproductive organs and omentum contained numerous tuberculous caseating granulomas. Mycobacteria were identified by Ziehl-Neelsen method. Antituberculosis treatment had been completed. In the differential diagnosis of an ovarian tumor and ascites TB should always be considered. It should also be suspected in recent Mycobacterium tuberculosis infection in younger women with amenorrhea, either HIV-seropositive or not.

2-DE protein expression in endometrial carcinoma

The objective of this study was to explore the protein expression pattern in normal endometrial mucosa (n = 5) and endometrial carcinoma (n = 15) of low (diploid) and high (aneuploid) malignancy potential by two-dimensional gel electrophoresis (2-DE). The specimens were evaluated for histopathologic subtype, stage and grade in relation to DNA ploidy. A match-set consisting of five samples from normal endometrium, eight diploid and seven aneuploid tumours was created. All the diploid and three of the aneuploid tumours were of endometrioid subtype, while the remaining four were of uterine seropapillary type. There were 192 protein spots differentiating diploid tumours from normal endometrium and 238 protein spots were separating aneuploid tumours from normal endometrium (p < 0.01). A cluster analysis based on 52 significantly deviating protein spots within the groups showed clustering and separation of the normal endometrium, diploid and aneuploid tumours. In conclusion this study showed significant differences in protein expression between normal endometrium and endometrial carcinoma as well as between endometrial carcinoma of low and high malignancy potential. In future studies these results may provide useful in finding new sensitive prognostic markers for endometrial cancer.

Local versus systemic effect of ovulation-inducing factor in the seminal plasma of alpacas

BackgroundCamelids are induced (reflex) ovulators. We have recently documented the presence of an ovulation-inducing factor (OIF) in the seminal plasma of alpacas and llamas. The objective was to test the hypothesis that OIF exerts its effect via a systemic rather than a local route and that endometrial curettage will enhance the ovulatory response to intrauterine deposition of seminal plasma in alpacas.MethodsFemale alpacas were assigned randomly to 6 groups (n = 15 to 17 per group) in a 2 × 3 factorial design to test the effect of seminal plasma versus phosphate-buffered saline (PBS) given by intramuscular injection, by intrauterine infusion, or by intrauterine infusion after endometrial curettage. Specifically, alpacas in the respective groups were given 1) 2 ml of alpaca seminal plasma intramuscularly, 2) 2 ml of PBS intramuscularly (negative control group), 3) 2 ml of alpaca seminal plasma by intrauterine infusion, 4) 2 ml of PBS by intrauterine infusion (negative control group), 5) 2 ml of alpaca seminal plasma by intrauterine infusion after endometrial curettage, or 6) 2 ml of PBS by intrauterine infusion after endometrial curettage (negative control group). The alpacas were examined by transrectal ultrasonography to detect ovulation and measure follicular and luteal diameters.ResultsIntramuscular administration of seminal plasma resulted in a higher ovulation rate than intrauterine administration of seminal plasma (93% versus 41%; P < 0.01), while intrauterine seminal plasma after endometrial curettage was intermediate (67%). None of the saline-treated controls ovulated. The diameter of the CL after treatment-induced ovulation was not affected by the route of administration of seminal plasma.ConclusionWe conclude that 1) OIF in seminal plasma effects ovulation via a systemic rather than a local route, 2) disruption of the endometrial mucosa by curettage facilitated the absorption of OIF and increased the ovulatory effect of seminal plasma, and 3) ovulation in alpacas is not associated with a physical stimulation of the genital tract, and 4) the alpaca represents an excellent biological model to evaluate the bioactivity of OIF.

Scanning electron microscopy of the endometrium of mares infused with gentamicin.

Scanning electron microscopy (SEM) was used to study the endometrium of nine 1-year-old thoroughbred mares after twice intrauterine infusions of gentamicin, on 2 consecutive days. Five mares were infused on 2 consecutive days with 40 ml gentamicin (50 mg/ml) mixed with 80 ml of normal saline. Four mares served as controls and were infused with 120 ml of saline on 2 consecutive days. Endometrial biopsies were obtained from all mares 3 days after the second intrauterine infusion. Each biopsy was processed for SEM by standard methods. The endometrial epithelium of the gentamicin-infused mares had more cellular perforations than the saline-infused mares. The gentamicin-infused mares had less and shorter microvilli. The ciliated cells were fewer and some ciliated cells had disrupted and some had drooping cilia. The endometrial epithelium of the gentamicin-infused mares had a considerable number of endometrial cells that lost their luminal surfaces and some that lost their microvilli, compared to the saline-infused mares. We suggest that the information gathered in this pilot study should be used as basis for further investigation, on a larger scale basis, of the effects of repeated intrauterine infusion of gentamicin on the endometrial mucosa of mares.

A New Technique of Hysteroscopic Myomectomy with Enucleation in Toto

Study Objective To determine the safety and effectiveness of a new technique for hysteroscopic resection of uterine submucous myomas with high intramural involvement (G2 type, European Society of Hysteroscopy classification). Design Prospective study (Canadian Task Force classification II-1). Setting University hospital. Patients Forty-four women. Intervention Hysteroscopic myoma enucleation in toto. Measurements and Main Results With a hysteroresectoscope and Collins electrode, an elliptic incision of endometrial mucosa that covers the myoma is made at the level of its reflection on the uterine wall until the cleavage zone of the myoma is reached. Connecting bridges between myoma and surrounding muscle fibers are resected. This allows nearly complete protrusion of the myoma into the uterine cavity, facilitating complete myomectomy by slicing. The procedure was performed in 41 (93.1%) of 44 women. Of these, 38 (92.6%) had myomas between 2 and 4 cm in diameter and 3 (7.4%) had myomas exceeding 4 cm. Mean operating time was 27 minutes (range 10–45 min). Conclusion This technique is efficient and allows complete resection of submucous myomas with large intramural component by favoring intracavitary protrusion of that part.

Wirkungen von Phytoöstrogenen und Mikronährstoffen auf menopausale Symptome - eine Beobachtungsstudie

Ziel der vorliegenden prospektiven, offenen Beobachtungsstudie war es, den Einfluss von Isoflavonen kombiniert mit ausgewählten Mikronährstoffen über 6 Monate auf typische klimakterische Symptome bei peri- und postmenopausalen Frauen zu untersuchen.

Pathophysiology of endometrial bleeding

Objectives: To review the morphological and molecular events responsible for uterine bleeding in health and disease. Methods: Review of pertinent literature focusing on the histology and pathophysiology of normal and abnormal uterine bleeding (AUB). Results: The seat of normal menstrual bleeding is located in the upper two-thirds of the endometrial mucosa and is recognized by tissue necrosis, disruption of microvasculature, migratory leukocytes and platelet/fibrin thrombi in microvessels. The molecular events responsible for tissue and vascular breakdown are related to the release of proteolytic lysosomal enzymes of endometrial cell and inflammatory cell origin. In cases of AUB, tissue breakdown is located in the superficial layer (subsurface) of the endometrium. It is either focal (breakthrough bleeding) or diffuse (withdrawal bleeding). It is initiated by either chronic endometritis and/or microerosions or vascular fragility due to structural abnormalities of microvessels. Endometritis and microerosions occur in otherwise normal endometrium, polyps, submucosal leiomyomata, atrophy and cancer (organic causes). Primary vascular alterations are found in hyperestrogenic-type endometria, i.e. anovulatory dysfunctional uterine bleeding (DUB) and progestational-type endometrium, i.e. progestational contraceptives and combined, continuous hormonal replacement therapy (HRT) (non-organic causes). Ovulatory DUB and coagulation disorders are not appreciated histologically. These are related to impaired vasoconstriction and fibrinolysis and impaired coagulation factors, respectively. Conclusions: Histology may contribute to better understanding of the mechanisms of action that initiate, regulate and lead to AUB. Better insight may trigger in the development of therapeutic procedures that could either prevent or control vascular breakdown which results in unexpected uterine bleeding.

Primary in situ squamous cell carcinoma of the endometrium, with extensive squamous metaplasia and dysplasia

Background. Primary squamous cell carcinoma of the endometrium is exceedingly rare. It has been described in association with pyometra but its etiology is still unclear. Case The authors report the case of a 75-year-old woman who presented with pelvic pain and pyometra. No gross tumor was identified in the uterus; however, extensive epidermalization of the endometrial mucosa was noted. Microscopic findings were consistent with a primary in situ squamous carcinoma of the endometrium associated with extensive squamous metaplasia and areas of dysplasia. HPV antigen and DNA detection were negative in both the endometrial lesions and the cervix. Conclusions These results support the sequence of change with squamous metaplasia, progressing through dysplasia to carcinoma as a possible pathogenetic process. HPV’s role, however, remains uncertain.

Effets sur l’endomètre des œstrogènes et des antiœstrogènes

Estrogens act through specific receptors located in the nuclei of epithelial and stromal cells of the endometrium. Estrogens stimulate the synthesis of these receptors and the progesterone inhibits their synthesis. Estrogens induce the proliferation of the mucosa during the proliferative phase. They also stimulate the synthesis of receptors for the progesterone, which is a prerequisite for progesterone activity. Hyperplasias most of the time do not contain cytological atypia and are developed under a hyperestrogenic background. They contain receptors for estrogen and progesterone, and are able to respond to progestogens. Hyperplasias with cytological atypia are precancerous lesions, associated with an hyperestrogenic or atrophic background. In the later case, they may be focal and are better diagnosed by hysteroscopy. They are best managed by simple hysterectomy. Progesterone may be used if the patient desires to conceive. Endometrial cancers are either associated with an hyperestrogenic or atrophic background. In the later case, they are often of serous or clear cell type. Endometrial effects of antiestrogens are known only for tamoxifene. Tamoxifene has an atrophic effect but sometimes may induce an estrogenic stimulation of the endometrial mucosa through the α and β estrogenic receptors. Polyp is the most frequent abnormality diagnosed but endometrial cancer is significantly more frequently diagnosed than in a control population. It is well differentiated and does not modify the survival of the patient.

Seroprevalence of an Endometriotropic Bovine Herpes Virus-4 in a Georgia Dairy

The University of Georgia Veterinary Diagnostic Laboratory has now confirmed more than 60 cases of suppurative, ulcerative endometritis associated with Bovine Herpesvirus-4 (BHV-4) in postparturient dairy cows. These cases have a clinical pattern of metritis that occurs 3 to 28 days postpartum. Beginning at 3 to 7 days postpartum, the uterus is characterized by necrotic, ulcerated endometrial mucosa with only mild inflammation in the lamina propria and submucosa. Over the ensuing 21 days, the ulcers become confluent/diffuse and epithelium is replaced by fibrinonecrotic, suppurative mats resulting in severe bacterial pyometra by day 24, usually involving Arcanobacterium pyogenes or Escherichia coli. In addition to the gross pathology, histopathologic evidence demonstrates viral inclusion bodies and virus detection techniques yield positive results for BHV-4.3 Before 1999, BHV-4-associated endometritis had rarely been recognized in the United States,4 but a syndrome of epizootic metritis similar in timing, course and outcome attributed to BHV-4 was reported in Europe in the 1980s.1,2,6 Significant seroconversion to BHV-4 occurs in affected herds. The viral sequence of this endometriotropic strain of BHV-4 differs from the BHV-4 strain that is associated with mild respiratory disease (DN599).3 Herds affected by this endometriotropic strain of BHV-4 have experienced high morbidity and mortality rates.3 One endemic dairy herd had a period mortality rate of 70% due to BHV-4- associated metritis (7 of 10 dead in one two-week interval). Due to concurrent or subsequent bacterial metritis associated with this viral infection, large economic losses are incurred from death, delayed breeding and infertility, discarded milk from antibiotic therapy, and decreased milk production from systemic effects of the metritis. Similar reports from other diagnostic laboratories indicate BHV-4 appears to be an emerging cause of endometritis in cattle throughout the southern and midwestern United States.

Correlation of survivin mRNA detection with histologic diagnosis in normal endometrium and endometrial carcinoma

Background. The objective of this study was to determine if survivin mRNA expression is a marker of endometrioid adenocarcinoma and if survivin mRNA levels correlate with tumor grade and stage. Methods. Twenty-six samples of endometrioid adenocarcinoma and 18 cases of benign endometrium were obtained at surgery. RNA was extracted from tissues and was used for quantitative real-time RT-PCR, targeting a 91-bp sequence of survivin mRNA and the levels were standardized to the levels of ribosomal RNA. Statistical analysis of the correlation between histologic diagnosis and the corrected survivin mRNA levels was performed by the Fisher Exact test and the Kruskal–Wallis test. Results. Survivin mRNA was detected in all specimens. Survivin mRNA levels were increased in proliferative endometrium (P = 0.0509) and was increased in correlation with ascending grade in endometrioid adenocarcinoma (P = 0.01). Conclusion. Survivin mRNA is not a specific marker of endometrial cancer, but may reflect an important mechanism in tumor progression of the endometrial mucosa.

The analyses of 17beta-hydroxysteroid dehydrogenase isozymes in human endometrial hyperplasia and carcinoma.

Intratumoral metabolism and synthesis of estrogens are considered to play very important roles in the pathogenesis and development of human endometrial adenocarcinoma. The 17beta-hydroxysteroid dehydrogenase (17beta-HSD) isozymes catalyze the interconversion of estradiol (E2) and estrone and thereby serve to modulate the tissue levels of bioactive E2. To elucidate the possible involvement of this enzyme in human endometrial carcinoma, we first examined the expression of 17beta-HSD type 1 and type 2 in 20 normal cycling human endometria, 36 endometrial hyperplasia, and 46 endometrial endometrioid adenocarcinoma using immunohistochemistry, and we then studied immunoreactivity of 17beta-HSD type 2 using immunoblotting analyses, the activity of 17beta-HSD type 1 and type 2 using thin-layer chromatography and their expression using RT-PCR in endometrial endometrioid adenocarcinoma. We correlated these findings with various clinicopathological parameters to examine the biological significance of 17beta-HSDs in human endometrial disorders. 17beta-HSD type 2 immunoreactivity in normal endometrium was present in all cases of secretory phase (n = 14), but not in any endometrial mucosa of proliferative phase (n = 6). In addition, 17beta-HSD type 2 immunoreactivity was detected in 27 of 36 (75%) endometrial hyperplasia and 17 of 46 (37%) carcinoma cases. 17beta-HSD type 1 immunoreactivity was not detected in all the cases examined. In both endometrial hyperplasia and carcinoma cases there were significant positive correlations between 17beta-HSD type 2 and progesterone receptor labeling index (LI). In carcinoma cases, a significant inverse correlation was detected between 17beta-HSD type 2 immunoreactivity and age. In addition, 17beta-HSD type 2 immunoreactivity was also correlated with 17beta-HSD type 2 enzymatic activity, and semiquantitative analyses of 17beta-HSD type 2 messenger RNA. No significant correlations were detected between 17beta-HSD type 2 and estrogen receptor LI, Ki67 LI, amount of aromatase messenger RNA or histological grade. These data indicated that the expression of 17beta-HSD type 2 in hyperplastic and/or neoplastic endometrium may represent altered cellular features through hyperplastic and neoplastic transformation. However, 17beta-HSD type 2 may also play some protective and/or suppressive roles toward unopposed estrogenic effects through inactivating E2 in situ, especially in premenopausal patients.

Accuracy of Hysteroscopy in Predicting Histopathology of Endometrium in 1500 Women

Study Objective To estimate the accuracy of hysteroscopy in predicting endometrial histopathology. Design Retrospective analysis (Canadian Task Force classification II-2). Setting Public hospital. Patients One thousand five hundred women undergoing diagnostic hysteroscopy for suspected endometrial pathology, mostly because of abnormal uterine bleeding. Interventions Hysteroscopy and endometrial biopsy. Measurements and Main Results Hysteroscopy imaging was matched with histology. Functional, dysfunctional, and atrophic endometrium were considered normal findings; endometritis, endometrial polyps, hyperplasia, and carcinomas were considered abnormal. Sensitivity, specificity, and negative (NPV) and positive (PPV) predictive values of hysteroscopy in detecting normal or abnormal endometrium were calculated. These figures were defined to assess hysteroscopic accuracy in estimating pathologic conditions. Histology showed normal endometrium in 927 patients. Endometritis, polyps, hyperplasia, and malignancies were found in 21, 265, 185, and 102 patients, respectively. Hysteroscopy showed sensitivity, specificity, NPV, and PPV of 94.2%, 88.8%, 96.3%, and 83.1%, respectively, in predicting normal or abnormal histopathology of endometrium. Highest accuracy was in diagnosing endometrial polyps, with sensitivity, specificity, NPV, and PPV of 95.3%, 95.4%, 98.9%, and 81.7%, respectively; the worst result was in estimating hyperplasia, with respective figures of 70%, 91.6%, 94.3%, and 60.6%. All failures of hysteroscopic assessment resulted from poor visualization of the uterine cavity or from underestimation or overestimation of irregularly shaped endometrium. Conclusion Hysteroscopy was accurate in distinguishing between normal and abnormal endometrium. Nevertheless, better knowledge of relationship between hysteroscopic imaging and pathophysiologic states of endometrium is necessary to improve its accuracy. Endometrial sampling is recommended in all hysteroscopies showing unevenly shaped and thick endometrial mucosa or an anatomically distorted uterine cavity, and when endouterine visualization is less than optimal.

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. © 1999 John Wiley & Sons, Inc. J Clin Ultrasound 27:541–543, 1999.

Microanatomy of the female reproductive organs in postmenopause by scanning electron microscopy

The detailed three-dimensional ultrastructural features of the reproductive organs of menopausal and postmenopausal women were studied by means of integrated transmission and scanning electron microscopy (SEM) and reported in a new colored microtopo-graphical fashion. These methods revealed significant alterations in the microanatomy of the various reproductive organs specifically related to the decline of plasma estrogen levels. In particular, the ovary progressively showed characteristic wide areas of loss of epithelium with consequent exposure of the underlying connective tissue. Both endometrial and tubal mucosa demonstrated a gradual but often dramatic decrease in the number of ciliated cells which was more evident in the tube. In addition, the non-ciliated (microvillous secretory) cells of the uterus, including both endocervix and tubal mucosa, became flattened and, in some instances, their apical poles developed unusual wrinkles (microridges or microplicae). The ectocervix and vaginal squamous cells presented a reduction in the number of their microridges and changes in the typical structural organization. These microtopographical results showed that the decline of estrogen during the menopause and postmenopause induces important and complex structural changes of the woman's reproductive system, much more detailed than those revealed to date by the use of only conventional optical and transmission electron microscopy (TEM). The three-dimensional findings offer the opportunity to re-evaluate the classic histopathology of the above aging organs using more refined microtopographical and morphophysiopathological parameters.

Identification of the ureter and dissection of the bladder pillar in laparoscopic-assisted radical vaginal hysterectomy

To determine the effect of tamoxifen on the endometrium in postmenopausal women with breast cancer and to try to identify, by pretreatment screening, subjects at higher risk of developing endometrial cancer. Between January 1993 and January 1996, 264 postmenopausal women with breast cancer were studied prospectively with pelvic ultrasonography. Outpatient hysteroscopy and endometrial biopsy were done if ultrasound abnormalities were detected. Initial endometrial evaluation was done before treatment with tamoxifen was started, 20 mg daily, and annually thereafter. Attention was focused on endometrial lesions and, especially, endometrial hyperplasia, which was defined according to World Health Organization classification. Endometrial hyperplasia was subdivided into two broad categories: hyperplasia without cytological atypia and hyperplasia with cytological atypia. Adenocarcinoma in situ was defined as a well-differentiated endometrial carcinoma confined to the endometrial mucosa without myometrial invasion. Forty-six women (17.4%) had asymptomatic endometrial lesions diagnosed before starting tamoxifen, and two of these were atypical lesions. Patients with initial lesions and those without initial lesions were followed separately. At 3 years of follow-up, the incidence of atypical lesions was significantly higher in women with lesions initially than in those without (three lesions among nine women versus one lesion among 51 women, P = .009). It appears that a group of high-risk subjects can be defined on the basis of endometrial evaluation before tamoxifen therapy; these women should be followed carefully because of the high incidence of severe atypical lesions.

Hyperplastic human endometrium

Endometrial hyperplasia is considered to be a frequent cause of menorrhagia. Traditionally, this pathology was diagnosed from specimens obtained by uterine curettage or after hysterectomy for benign disease. With hysteroscopy one can visualize the uterine cavity directly and perform guided biopsies of the endometrial mucosa. We assessed the reliability of hysteroscopic procedures in the diagnosis of endometrial hyperplasia. We performed 980 hysteroscopies in 3 years for menorrhagia and found endometrial hyperplasia in 128 women. We compared the results with histologic findings. Statistical analysis was performed according to McNemar test. On the basis of the results, hysteroscopy diagnoses and monitors endometrial hyperplasia.

Human Papillomavirus Detection of Endometrioid Carcinoma with Squamous Differentiation of the Uterine Corpus

Many studies have shown a link between human papillomavirus (HPV) and cervical carcinoma. However, studies on the association of HPV with endometrioid carcinoma of the corpus uteri are sparse and controversial. In this study, 33 formalin-fixed, paraffin-embedded tissue samples of endometrioid carcinoma with squamous cell differentiation in grade 1 (adenoacanthoma) and 10 additional samples of endometrioid carcinoma with less squamous cell differentiation in grade 2 or 3 (adenosquamous carcinoma) were examined by the hybrid capture system for the presence of the 14 most common anogenital HPV types, consisting of low-risk HPV types 6, 11, 42, 43, and 44, and intermediate- and high-risk HPV types 16, 18, 31, 33, 35, 45, 51, 52, and 56. No evidence of high-risk HPV DNA types was found in any of these samples. The low-risk HPV DNA types were found in three samples and showed borderline results (±) in 6 samples by the hybrid capture system. The 43 samples were tested by dot blot hybridization with HPV probes 6/11, 16/18, and 31/33/35. Only 1 sample was positive for HPV 6/11. The results of this study did not indicate an association between HPV infection and endometrioid carcinoma with squamous cells, though the endometrial mucosa of the corpus uteri is anatomically connected to the endocervical epithelium, and in some cases HPV has been postulated to possibly cause squamous cell differentiation of the endometrium. Our findings are in accord with the concept that HPV infection leading to malignancy is highly site- and tissue-specific. In conclusion, the endometrium may not be a suitable host epithelium for HPV replication and maturation.

Goserelin

Goserelin is a gonadotrophin-releasing hormone (GnRH) analogue which, during continuous administration, down-regulates the pituitary-ovarian gonadal axis and reduces levels of the gonadotrophins, luteinising hormone and follicle-stimulating hormone. In women, this results in suppression of ovarian steroidogenesis and a decline in estrogen to levels similar to those observed after menopause or following surgical oophorectomy. Thus, goserelin has a useful role in the management of some benign estrogen-dependent gynaecological disorders. Goserelin is available as a biodegradable sustained release depot 3.6mg injection which is administered every 28 days. In women with endometriosis, monthly injections of depot goserelin were effective in achieving resolution of endometriotic implants and in improving pelvic symptoms, including pain and dyspareunia. Randomised clinical comparisons of depot goserelin with danazol indicate that goserelin is at least as effective as danazol and is better tolerated in the treatment of endometriosis. In the management of uterine leiomyomata (fibroids), goserelin depot injections reduce uterine size and the size of uterine leiomyomata, with maximum clinical benefit achieved approximately 3 to 4 months after initiation of treatment. When used as an adjunctive pretreatment for women undergoing surgical removal of uterine leiomyomata, goserelin was associated with technically easier surgical procedures, reduced intraoperative blood loss and reduced transfusion requirements around the time of surgery. As an alternative to surgery, therapeutic use of goserelin is limited by the rapid regrowth of leiomyomata following cessation of treatment. However, goserelin may be a useful treatment for women approaching menopause, in whom uterine leiomyomata shrink naturally as endogenous estrogen levels decline. In women with dysfunctional uterine bleeding, treatment with depot goserelin before surgery facilitates resection and ablative procedures by suppressing endometrial growth and thinning the endometrial mucosa. Goserelin is also an effective alternative to surgery in this patient group. As adjuvant therapy for women undergoing assisted reproduction procedures, goserelin is associated with reduced cycle cancellation rates and with an increase in the rate of oocyte retrieval. The tolerability profile of goserelin is characterised by adverse effects typical of hypoestrogenism, including hot flushes, loss of libido and loss of bone mineral density. However, concomitant 'add-back' hormone replacement therapy appears to effectively reduce these hypoestrogenic symptoms. In summary, the availability of depot goserelin has broadened the spectrum of effective treatments for benign estrogen-dependent gynaecological disorders. As goserelin is effective as a sustained release depot formulation suitable for administration on a monthly basis, it is also a convenient and practical treatment choice.