Simplified artificial endometrial preparation,using oral estradiol and novel vaginal progesterone tablets: a prospective randomized study

There are various successful protocols for artificial endometrial preparation, comprising induction of endometrial proliferation with estrogens and secretory transformation with progestins. The aim of this prospective randomized study was to evaluate a simplified approach for endometrial preparation, comparing two constant doses of oral estradiol combined with a novel low-dose vaginal natural progesterone preparation (100 mg Endometrin^® tablets). Twenty-nine patients were enrolled in the study and divided randomly into two groups. Both groups received oral estradiol tablets from the beginning of menstruation, group A (15 patients) receiving 4 mg/day divided into two doses of 2 mg each, and group B (14 patients) receiving 6 mg/day divided into three doses. Serum estradiol and progesterone and sonographic thickness of the endometrium were measured on the 1st day of menstruation and on the 6th, 11th, 16th and 21st days of the artificial cycle. Following the first 12 days of estradiol priming, with an endometrial thickness of ≥ 8 mm, Endometrin vaginal tablets 100 mg were added twice a day for 10 days. On the 21st cycle day, an endometrial biopsy was taken from all patients using Pipelle^®. In all 29 patients, appropriate changes in estradiol, progesterone and endometrial thickness were observed. Estradiol levels were significantly higher in the 6 mg/day group on days 6 and 11, but no significant difference was noted in serum progesterone level and endometrial thickness between groups. Histological evaluation of endometrial biopsies, on the 21st day, revealed adequate late-secretory endometrium in 14/15 (93.3%) patients of group A and in 13/14 (92.9%) patients of group B. In conclusion, our results demonstrate that an appropriate endometrial secretory transformation may be induced using an economical regimen of fixed low-dose oral estradiol (4 mg/day) and low-dose vaginal progesterone tablets (Endometrin 100 mg twice daily).     

Long-term treatment of leiomyomas with gestrinone

A prospective randomized study was conducted in 100 women with leiomyomas in order to evaluate the effect of gestrinone, a synthetic derivative of ethynil-nor-testosterone. Patients in group A received capsules containing 2.5 mg of gestrinone three times weekly orally. Those in group B received capsules containing 5.0 mg twice weekly, also orally. In group C, patients used by vaginal route tablets containing 5 mg of gestrinone three times weekly. Reduction in uterine volume occurred in all three groups of patients. Of patients who discontinued treatment at 6 months, uterine volume remained lower than pretreatment values in 89%, 18 months after discontinuation. Of those patients who discontinued at 1 year, uterine volume remained below pretreatment levels in 76% 1 year after discontinuation. In patients treated continuously for 24 months, mean uterine volume decreased from a mean 339 cm3 to 273 cm3, a statistically significant difference. The vaginal route showed statistically more significant volume decreases than the oral route for all treatment intervals.     

Rollerball Endometrial Ablation: A Histological Study in Danazol Pretreated Patients

Summary: Endomyometrial biopsies were taken from danazol pretreated patients about to undergo rollerball endometrial ablation for menorrhagia. The biopsies were taken with a loop electrode at hysteroscopy before and after 1, 2, 3 passes of a rollerball electrode over the endometrium using powers of electrocoagulation diathermy varying from 30 to 100 watts. The biopsies were then assessed histologically. Nineteen biopsies from the perceived endocervical canal, 25 posttreatment curettings and 3 hysterectomy specimens were also assessed. Biopsies taken after danazol pretreatment but before diathermy showed a thinned inactive endometrium. A histological classification of the effect of electrocoagulation diathermy on the endometrium was developed describing increasing endometrial damage. The degree of endometrial damage was directly related to the number of rolls of the ball over the endometrium and to the power of electrocoagulation diathermy. Endometrium was found in 84% of biopsies from the perceived endocervical canal and endometrium was found in curettings from 3 of 11 patients who were amenorrhoeic following ablation.     

Tamoxifen and endometrial pathologies: a prospective study.

OBJECTIVE:The purpose of this study was to prospectively follow a group of women with breast cancer, on tamoxifen, for the development of endometrial pathologies. MATERIALS AND METHODS: Eighty women with breast cancer, on tamoxifen, were prospectively followed every 6 months with pelvic examination, Pap smear, vaginal ultrasound, and endometrial biopsy. RESULTS: Nine women were lost to follow-up prior to initiation of treatment and 4 refused biopsies, leaving 67 patients for evaluation. Fifty (74.6%) of the 67 patients were already on tamoxifen for a mean duration of 15.8 +/- 16.6 months and had a baseline benign, unremarkable endometrium at the time of entry into the study. The total duration of treatment was 32.5 +/- 19.6 months (median 30 months). The mean age of the patients was 51.7 +/- 9.9 years (median 52 years). Of the patients, 56.7% were postmenopausal. Sixty-three patients had a benign endometrium (mean age 51.8 +/- 10.1 years, mean duration 33.1 +/- 19.6 months). Two patients had simple hyperplasia (mean age 43.5 years, duration 28.5 +/- 33.2 months), 1 patient had complex hyperplasia with atypia (age 57 years, duration 13 months), and another patient developed adenocarcinoma (grade 3) after 22 months. These 4 patients had abnormal vaginal bleeding. Seven patients developed endometrial polyps (mean age 54.0 +/- 8.5 years, duration 36 +/- 24.2 months). The mean endometrial thickness for patients with histologically unremarkable and abnormal endometrium was not significantly different (7.6 +/- 3.9 vs 8.8 +/- 5.0 mm, respectively) (median 7.0 mm for both groups). No endometrial thickness cutoff point reached statistical significance. The patient who developed endometrial cancer had a thickness of only 3 mm. CONCLUSION: All patients who developed an abnormal endometrium had abnormal vaginal bleeding. There was no correlation between endometrial thickness and endometrial pathology; thus the value of routine screening remains controversial.     

Maturation of Vaginal and Endometrial Epithelium in Postmenopausal Breast Cancer Patients Receiving Long-Term Tamoxifen

To assess the estrogenic effects of tamoxifen on vaginal and endometrial epithelium and to investigate whether these changes are associated with any pathological findings in the endometrium, 53 postmenopausal breast cancer patients receiving long-term tamoxifen and 52 control breast cancer patients without any hormonal treatment were examined. Pathological findings in the endometrium were evaluated by hysteroscopy and curettage. The main outcome measures were the maturation index in Papanicolaou (Pap) smears, estrogen-like epithelial changes in the endometrium, serum concentrations of gonadotropins, sex hormone-binding globulin (SHBG), estradiol (E2), and testosterone (T). Informative Pap smears showed estrogenic effects in 89% (41/46) of the tamoxifen group and in 49% (22/45) of the control group, and in endometrial aspiration samples in 71% (32/45) and in 41% (19/46), respectively. These changes were associated with increased concentrations of serum E2 in the control group but not in the tamoxifen group. All five patients (11%) with endometrial polyps in the control group showed estrogenic endometrial changes, whereas among 14 women with polyps in the tamoxifen group, 9 showed estrogenic changes and 5 endometrial atrophy. Endometrial adenocarcinoma was found in 3 patients in the tamoxifen group and in 2 in the control group. Pap smears showed atrophy in 2 patients in the former and in one in the latter group. These findings confirmed estrogen-like effects of tamoxifen on the vaginal and endometrial epithelium in postmenopausal breast cancer patients, but these were not closely associated with benign or malignant endometrial lesions.     

"Ovulation during lactation" as determined by endometrial biopsy

A study was conducted at the Lady Hardinge Medical College and Hospital in New Delhi, India with the objective of determining the frequency of ovulation during lactation. It is now accepted that the most satisfactory proof of ovulation is the presence of a secretory endometrium late in the menstrual cycle. The histology of endometrium was the only method of study for the presumptive evidence of ovulation employed in this investigation. Out of a total of 197 endometrial biopsies, 77 were obtained from menstruating women, and 120 were obtained from women who had amenorrhea. Of these 98 were taken during lactational amenorrhea in 89 cases. Out of 77 biopsies from the menstruating group, 30 were obtained from 26 lactating mothers. The biopsies during amenorrhea of lactation showed that the proportion of biopsies revealing inactive endometrium increases with the duration of amenorrhea. It was also observed that it is often impossible to obtain any endometrial tissue if the period of amenorrhea has been prolonged. In 31.6% of the specimens there was no sign of growth or activity of the endometrium. The endometrium corresponding to late and midproliferative phase was found only if the biopsy was taken within 3 months after delivery. 16% of the 1st cycles in lactating mothers were ovular (total 12 biopsies) and 57% of 1st cycles in nonlactating women were ovular. The finding suggests that lactation does inhibit ovulation in addition to postponement of menstruation. Few biopsies were available for the subsequent cycles. In lactating women, 50% of the 2nd cycles and 83% of the 3rd cycles were ovular. In a fully lactating mother the earliest ovular biopsy was detected at 9 weeks postpartum. In 1 partially lactating and 3 nonlactating cases, ovular biopsies were obtained at 41 days postpartum. The endometrium tends to be atrophic as amenorrhea is prolonged, but this atrophy is reversible.     

Cytologically benign endometrial cells in the papanicolaou smears of postmenopausal women

OBJECTIVE: The objective of this study was to determine the clinical significance of the presence of benign endometrial cells in the Pap smears of postmenopausal women. METHODS: A retrospective analysis of the clinical outcome of 297 postmenopausal women containing benign endometrial cells in their Pap smears was performed. All patients had subsequent endometrial biopsies or routine follow-up for 1-5 years. In addition, Pap smears of 253 of the patients were reviewed with particular reference to the morphology and type of the endometrial cells. Immunohistochemical staining with CD68 was performed in 15 selected cases to determine the origin of the stromal cells. RESULTS: One hundred thirty-two (44%) women had endometrial biopsies while the remaining 165 (56%) were followed up by routine gynecologic examinations and repeat Pap smears. Endometrial lesions were detected in 14 patients of whom only 3 had significant lesions (2 atypical hyperplasias and 1 adenocarcinoma). Review of the Pap smears revealed benign superficial endometrial stromal cells in most cases (73%). Stromal cells showed CD68 positivity indicating a histiocytic origin. Glandular cells were present in 27%, either alone or in association with stromal cells. Statistical analysis revealed that the presence of endometrial glandular cells in Pap smears was associated with five times the likelihood of significant endometrial disease than found in women with normal Pap smears, although sensitivity and positive predictive value were very low (7.14 and 2.94%, respectively). Superficial endometrial stromal cells were not useful in predicting endometrial pathology. CONCLUSION: Significant endometrial lesions were present in 1% of postmenopausal women containing morphologically benign endometrial cells in the Pap smears. In the majority, the endometrial cells were of the superficial stromal type, which were demonstrated immunohistochemically to be histiocytes. The presence of endometrial glandular cells correlated significantly with endometrial pathology. Such an association was not observed in cases with stromal cells only.     

Prognostic value of persistent cancer cells in vaginal smears of patients with cervical carcinoma treated by radiotherapy

In an attempt to improve the therapeutic scheme in cervical carcinoma a clinical research program involving 100 patients with stages 1 and 2 of cervical carcinoma was started. All patients underwent radiation treatment only. In the series 32 patients were state 1 and 68 stage 2. About 1/2 had undifferentiated squamous epithelioma and the others moderately differentiated epthelioma. Radiotherapy consisted of intracavity radium of 5000 mg-hr. and an external telecobalt irradiation up to 4000 rad tumor dose through 4 portals. During and after radiotherapy patients were followed by clinical examiniations and vaginal smears. Months after beginning of treatment another cervical punch biopsy was done. The 3 year recovery rate was 97% of stage 1 but only 75% of stage 2 patients. Recovery seemed better in well differentiated epithelioma and in cases treated first with external radiation. There were 13 deaths from recurrent disease within 5 to 35 months after begining of treatment. Punch biopsies performed 4 months after beginning of treatment revealed carcinomatous tissue in the cervical area of only 2 of these 13 patients. In all 87 survivors, abnormal cells disappeared from vaginal smears by 7 weeks. In the 13 fatal cases, abnormal cells persisted for 7 weeks or beyond. In 5 of the 13 fatal cases, tumor cells in the vaginal smears persisted throughout the remainder of the patients' lives. Other follow-up methods seemed inefficient cases. Well defined vaginal cytology seemed of most prognostic value. The radioresistent group could be submitted to complementary surgical treatment to improve the prognosis.     

Diagnosis and management of out-of-phase endometrial biopsies among patients receiving clomiphene citrate for ovulation induction

Eighty-seven patients who underwent a late secretory phase endometrial biopsy while taking clomiphene citrate (CC) for ovulation induction were studied. Of the endometrial biopsies, 21 (24%) showed an endometrium greater than 2 days out of phase (OOP) with respect to the subsequent menstrual cycle. All 87 patients were categorized by age, weight, CC dosage, and underlying disease entity. The patients then were evaluated by these categories in relation to the incidence of an OOP biopsy while taking CC. Patients with a diagnosis of hypothalamic amenorrhea were statistically more likely to have an OOP endometrium. No other subgroup showed an increased or decreased incidence of OOP biopsies. Conception and spontaneous abortion rates were similar among patients with in-phase biopsies and those with out-of-phase biopsies, which subsequently were corrected with further medical therapy. An aggressive approach to the diagnosis and treatment of luteal phase insufficiency in patients who receive CC for ovulation induction is recommended.     

Estrogens, progestogens and endometrial cancer.

At the Wilford Hall U.S. Air Force Base Medical Center, Texas, about 4000 postmenopausal women received estrogen replacement therapy during 1975. Of these, 2700 took estrogens only and 1240 were given a progestogen along with estrogen. Hysterectomy had been done previously on 1700 patients (42%), leaving 2300 with intact uteri and a risk of endometrial cancer. Adenocarcinoma of the endometrium was diagnosed in 7 patients. Of these, 6 had received estrogen therapy. There was 1 endometrial malignancy in a patient also receiving a progestogen. Among 510 untreated postmenopausal women with intact uteri, 1 adenocarcinoma of the endometrium was found. Type and dosage of estrogen were unrelated to endometrial malignancy. In addition to the 7 endometrial cancers from the clinic, 22 cases were diagnosed elsewhere and referred for treatment, 11 of these had received no hormones. 10 were taking estrogens and 1 was receiving Oracon for birth control. The incidence of endometrial malignancy in the U.S. is reported to be 21/100,000 women/year. There is a 3-fold to 9-fold increased risk of endometrial cancer associated with obesity alone. The probability that untreated postmenopausal women with intact uteri will develop carcinoma of the endometrium is 1/1000/year. With estrogen users, it is reported to be increased -7.6/1000 women/year. In the author's clinic during 1975, the incidence among those receiving only estrogen was 4.7/1000. Among those also receiving a progestogen the incidence was .8/1000. Unopposed estrogens apparently have a role in the etiology of endometria hyperplasia and neoplasia through incomplete shedding of the endometrium. Progesterone produces more complete sloughing of the endometrium and also converts all degrees of hyperplasia into secretory endometrium. Nulliparity, infertility, and anovulation are predisoposing factors to endometrial carcinoma. Progestogens are palliative therapy for endometrial cancer.     

Simplified artificial endometrial preparation, using oral estradiol and novel vaginal progesterone tablets: a prospective randomized study.

There are various successful protocols for artificial endometrial preparation, comprising induction of endometrial proliferation with estrogens and secretory transformation with progestins. The aim of this prospective randomized study was to evaluate a simplified approach for endometrial preparation, comparing two constant doses of oral estradiol combined with a novel low-dose vaginal natural progesterone preparation (100 mg Endometrin tablets). Twenty-nine patients were enrolled in the study and divided randomly into two groups. Both groups received oral estradiol tablets from the beginning of menstruation, group A (15 patients) receiving 4 mg/day divided into two doses of 2 mg each, and group B (14 patients) receiving 6 mg/day divided into three doses. Serum estradiol and progesterone and sonographic thickness of the endometrium were measured on the 1st day of menstruation and on the 6th, 11th, 16th and 21st days of the artificial cycle. Following the first 12 days of estradiol priming, with an endometrial thickness of > or = 8 mm, Endometrin vaginal tablets 100 mg were added twice a day for 10 days. On the 21st cycle day, an endometrial biopsy was taken from all patients using Pipelle. In all 29 patients, appropriate changes in estradiol, progesterone and endometrial thickness were observed. Estradiol levels were significantly higher in the 6 mg/day group on days 6 and 11, but no significant difference was noted in serum progesterone level and endometrial thickess between groups. Histological evaluation of endometrial biopsies, on the 21st day, revealed adequate late-secretory endometrium in 14/15 (93.3%) patients of group A and in 13/14 (92.9%) patients of group B. In conclusion, our results demonstrate that an appropriate endometrial secretory transformation may be induced using an economical regimen of fixed low-dose oral estradiol (4 mg/day) and low-dose vaginal progesterone tablets (Endometrin 100 mg twice daily).     

Artificial versus stimulated cycles for endometrial preparation prior to frozen-thawed embryo transfer

The objective of this study was to compare the implantation rate, pregnancy rate and endometrial thickness of frozen-thawed embryo transfers using endometrial preparation with either an artificial cycle or stimulated cycle. This was a prospective randomized trial at a single academic IVF centre. Seventy-seven patients undergoing artificial cycles received oral oestradiol; patients with endometrium < 7 mm on day 9-10 were switched to vaginal oestradiol. Eighty-six patients undergoing stimulated cycles received recombinant FSH followed by human gonadotrophin hormone injection. Vaginal progesterone was begun 2 or 3 days prior to embryo transfer. There was no difference in implantation rate (8.5% versus 7.3%), pregnancy rate (16% versus 13%), cancellation rate (both 23%) or endometrium thickness (8.7 +/- 1.1 mm versus 8.7 +/- 1.0 mm) between artificial and stimulated cycles. Stimulated cycles had a higher incidence of thin endometrium (27% versus 5%, P < 0.01). In artificial cycles, patients switched to vaginal oestradiol had improved pregnancy rate (31%) versus patients who received oral oestradiol alone (13%) (P = 0.05). It is concluded that artificial and stimulated cycles produce comparable pregnancy rates, implantation rates, cancellation rates and endometrial thickness, although stimulated cycles have a higher incidence of thin endometrium. Vaginal oestradiol supplementation improved implantation rates.     

The significance of atypical glandular cells on routine cervical cytologic testing in a community-based population

OBJECTIVES: We sought to determine the follow-up rate of women with glandular atypia on routine Papanicolaou smears in a community-based population and to describe the associated pathologic findings. STUDY DESIGN: Over a 12-month period, all patients with Papanicolaou smears with atypical glandular cells of undetermined significance were reviewed for demographic and clinical characteristics and followed up for a period of 12 to 24 months. RESULTS: Of the 48,890 Papanicolaou smears examined, 141 (0.29%) were diagnosed with atypical glandular cells of undetermined significance. Of these, 22 (17.6%) had no record of any subsequent investigation, and only 64 (51.2%) were monitored with both colposcopy and biopsy. Of the 64 biopsy specimens, 39 (60.9%) were positive for disease. Twenty-six (66.7%) were of squamous origin, with the most advanced lesion being cervical intraepithelial neoplasia 3. An additional patient had a combined cervical intraepithelial neoplasia and adenocarcinoma in situ lesion. Four (10.3%) additional patients had glandular cervical lesions, 2 benign polyps and 2 adenocarcinoma in situ lesions. Seven (17.9%) patients had endometrial lesions (benign polyps, 2 patients; complex atypical endometrial hyperplasia, 1 patient; and endometrial carcinoma, 4 patients). One patient had ovarian cystadenocarcinoma. Postmenopausal women were 5 times more likely to have a glandular lesion. Women with abnormal vaginal bleeding were also more likely to have a glandular lesion. These same patient groups were also more likely to have endometrial disease. CONCLUSION: The incidence of atypical glandular cells of undetermined significance on Papanicolaou smears in this community-based population was 0.29%, which is consistent with estimates from institution-based populations. Nearly 50% of women studied were not followed up with tissue biopsy. Of those with a tissue biopsy, 61% had positive findings, including 5 with cancer. Although postmenopausal status and abnormal vaginal bleeding were associated with endometrial or glandular disease, studies of larger patient populations should be conducted to examine potential risk factors for these conditions.     

Effectiveness and tolerance of depot leuprorelin acetate for preoperative endometrium flattening before endometrial ablation. German Leuprorelin Study Group

OBJECTIVE: In order to assess the efficacy and tolerability of leuprorelin acetate depot in pre-operative flattening of the endometrium prior to hysteroscopic endometrial ablation, 94 patients from eight centres were included in the per protocol analysis. MATERIAL AND PATIENTS: The patients included were pre- or peri-menopausal, had completed their family planning and had intractable uterine bleeding. The primary target criterion was the reduction in maximum endometrial thickness after two injections of leuprorelin acetate depot with an interval of four weeks between injections. Surgery took place two weeks after the second injection. RESULTS: Sufficient pre-treatment was achieved in 91.5% of the patients with > 50% decrease and/or a type 1 endometrium according to sonographic and/or endometrial atrophy (Score 11) according to the central histological evaluation. The endometrium was flattened by a mean of 4.0 +/- 4.1 mm. In terms of clinical response, amenorrhoea, hypomenorrhoea or normal menstruation were achieved after endometrial ablation. Hence 91.5% of patients benefited from the overall treatment after six weeks and still 83% after six months. The trial medication was well tolerated overall. The most common side-effect described was hot flushes which could be attributed to the deliberate oestrogen withdrawal. CONCLUSION: In view of the good study results, hormone-suppressive pretreatment of the endometrium can be recommended prior to elective ablation. Surgery should take place during the oestrogen-suppressed phase.     

Sequential radiation changes in cytology of vaginal smears in carcinoma of cervix uteri during radiotherapy

The study deals with acute/immediate radiation changes in 2020 sequential vaginal smears in 101 patients of carcinoma of the cervix uteri, 97 were of squamous cell carcinoma and 4 of adenocarcinoma. The smears were collected after 12-14 days, 15-24 days and 25 days to 6 weeks following radiotherapy. The pretreatment vaginal smears were collected and examined for percentage of cancer cells. Subsequent smears were studied for radiation changes in benign and malignant cells, such as cell size, vacuolation of cytoplasm, multinucleation and nuclear changes, etc. A gradual and linear decline in cancer cells was observed until the end of therapy; 41.6% of patients had less than 10% cancer cells within 12-14 days of therapy, 63.4% of patients between 15 and 24 days and 74.6% after 25 days to 6 weeks following radiation. Eighty three percent of the patients attained zero level at the end of therapy.     

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.     

Vaginal micronized progesterone in continuous hormone replacement therapy. A prospective randomized study

BACKGROUND: In the non-hysterectomized post-menopausal woman undergoing estrogen replacement therapy, the co-administration of a progestogen is mandatory to counteract the estrogenic proliferative effect on the endometrium. Metabolic and tissue effects of the various progestins vary with dosage and route of administration. This study was performed to evaluate the effects of selected progestins on the lipidic profile and endometrial morphology. METHODS: This is a prospective randomised study including 60 post-menopausal women undergoing hormonal replacement therapy (HRT). All patients received transdermic ethinil-estradiol in a continuous schedule. The utilized progestogens were: medroxyprogesterone acetate (MPA) 10 mg p.o. 12 days/month, transdermic nor-ethisterone acetate (NETA) 0.25 mg integrated in the ethinil-estradiol patches for the last two weeks of each cycle, micronized progesterone (MP) 100 mg transvaginally 12 days/month. RESULTS: None of the tested protocols significantly altered the lipidic profile of this group of patients. We noticed different effects on the estrogen stimulated endometrium elicited by the different progestinic regimens. While the cyclic administration of oral MPA or transdermic NETA more frequently resulted in endometrial atrophy, the trans-vaginal administration of MP more often induced (p<0.005 at six-month and p <0.001 after 1 year) a functional-like secretive endometrium. CONCLUSIONS: Micronized progesterone, cyclically administered in the form of a vaginal cream, offers an acceptable and effective alternative for women on continuous HRT wishing to maintain their monthly cycle.     

Oncogenic potential of tamoxifen on endometria of postmenopausal women with breast cancer--preliminary report

Tamoxifen (TAM), a nonsteroidal antiestrogen, is used for pre- and postmenopausal patients with breast cancer. Recent reports suggest that TAM may cause endometrial neoplasia. This study is designed to evaluate the oncogenic potential of low-dose TAM on the endometrium. Initially, endometrial screening of patients with breast cancer who had received TAM therapy for at least 12 months was conducted. Seventy patients were interviewed and office endometrial biopsies were obtained from thirty-eight patients. Seven (18%) had hyperplastic changes, ranging from simple hyperplasia through complex hyperplasia with atypia. The following prospective study was conducted: after breast surgery and prior to initiation of TAM therapy, an office endometrial sampling was obtained as a control. After initiation of TAM therapy, biopsies were repeated every 4 to 6 months as long as the patients remained asymptomatic. Nineteen patients were interviewed. Twelve patients were biopsied and followed from 3 to 15 months. One patient refused additional biopsies. Eleven patients had repeat biopsies after initiation of TAM. New hyperplastic changes were found in 3/11 (27%) patients. The preliminary results of this study (although with a small number of patients) indicate that TAM may have some neoplastic effect on the endometrium of postmenopausal patients with breast cancer. This study is still in progress. Additional prospective studies are warranted before a significant correlation between TAM and endometrial neoplasia is confirmed.     

Verrucous carcinoma of the endometrium: case history, pathologic findings, brief review of literature and discussion

BACKGROUND: Verrucous carcinoma is a rare condition. A defined disease of the oral cavity, larynx, esophagus, skin, vulva, vagina and cervix. But a verrucous carcinoma arising from the endometrium without evidence of cervical malignancy or endometrial adenocarcinoma is extremely rare. CASE: A 67-year-old G2P2 menopausal patient that was referred for consultation 1 year after presenting with vaginal bleeding to her gynecologist who subsequently underwent several endometrial biopsies where the pathological findings were repetitively similar: papillary squamous proliferation, cytologically bland with low mitotic activity but extensive proliferation. A hysterectomy with bilateral salpingo-oophorectomy was performed. The final histologic examination revealed a squamous cell carcinoma of endometrium, verrucous and well differentiated, and there was no cervical invasion identified. CONCLUSION: This is a rare form of endometrial cancer with apparent favorable prognosis that must be considered when squamous cells are identified on endometrial samplings.     

Cytologic changes following the use of oral contraceptives

Abnormal cytologic findings in gynecologic smears were more common among patients using oral contraceptives than among control patients. Cytologic examination should be routinely performed before oral contraceptives are prescribed. The exfoliation of endometrial cells was essentially the same between control and oral contraceptive patients. No evidence of excessive stimulation of epithelial element in endometrium accompanied the continued use of hormonal contraceptives. In general, the cytohormonal effect associated with oral contraceptives showed a depressed superficial cell count in the vaginal smears. Teenagers using oral contraceptives constituted 2 to 3% of the surveyed group. Long-term effects of antiovulatory drugs in young females are yet to be observed.