[Suicidal adolescents can benefit from Family Group Conferences]. / Eigen Kracht-conferenties bij suïcidale adolescenten.

A risk factor among suicidal adolescents is generally their inability to form and maintain relationships with other people. In the case that we investigated, the technique known as Family Group Conference (FGC) was used successfully to break through the adolescent's passivity and social isolation. The FGC also helped to alter the adolescent's conviction of being a burden to relatives, friends and other people. The results are in line with additional studies that used FGC with other target groups. This case study suggests that FGC is a promising type of intervention that can reduce the passivity and isolation of suicidal adolescents, strengthening their relationships and boosting a feeling of belonging. These factors as well as the results of the case investigated are currently stimulating further research into the use of FGCs to foster feelings of belonging and togetherness among suicidal adolescents.

Limited numbers of apoptotic cells in fresh paraffin embedded bone marrow samples of patients with myelodysplastic syndrome.

In myelodysplasia (MDS) the precise mechanism of ineffective erythropoiesis is not fully elucidated, but it is suggested that apoptosis may contribute to this process. We performed TdT-mediated dUTP-nick end labelling (TUNEL) staining of paraffin embedded bone marrow specimens to assess the amount of apoptotic cells in 21 MDS patients (7 RA, 3 RARS, 5 RAEB, 3 RAEB-T, 3 CMML) and five normal controls. In 10 MDS patients the TUNEL assay was performed in combination with immunostaining for Glycophorin-A (GpA) to determine apoptosis in the maturing erythroid compartment. To assess the proliferation of the bone marrow cells the expression of Ki-67 antigen was used as a marker. The mean apoptotic index (AI) in MDS patients was not increased (2.3 +/- 3.0% in MDS versus 4.8 +/- 1.2% in normal controls (P < 0.05)). Moreover, no significant difference in mean AI was observed in the GpA+ compartment between MDS and normal controls (0.8 +/- 0.2% versus 0.6 +/- 0.1%). In addition the different FAB-classifications and the different International Prognostic Scoring System (IPSS)-risk groups showed no significant differences between the subgroups. The expression of Ki-67, as marker for proliferative activity, in the GpA+ compartment from MDS did not differ significantly from normal controls (84.0 +/- 12.2% versus 79.9 +/- 20.2%). Our findings suggest that the observed increased apoptosis in in vitro culture assays is related to the detachment of the cells from the microenvironment leading to an increased susceptibility to apoptosis.

Obstetric outcome of singleton pregnancies after IVF: a matched control study in four Dutch university hospitals.

In singleton pregnancies after IVF a high rate of preterm deliveries and an increased rate of small-for-gestational age (SGA) children in comparison to the general parturient population have been reported. However, due to differences between IVF mothers and their peers who conceived naturally, careful selection of the control group is necessary to assess whether IVF pregnancies really carry increased risks of adverse outcome. In our study 307 IVF pregnancies were compared with 307 control pregnancies after elaborate matching for an extensive number of maternal characteristics, as well as for the hospital that provided the obstetric care. Four Dutch university hospitals contributed to the study. In cases with spontaneous onset of labour, gestational age at delivery was 3 days shorter in the IVF group (275 versus 278 days, P = 0.05). The proportion of SGA was higher in the IVF group (16.2 versus 7.9%, P < 0.001). The combination of these two results denotes a distinct difference between IVF and control pregnancies. Placental weight was comparable in both groups.

Obstetric outcome of twin pregnancies after in-vitro fertilization: a matched control study in four Dutch university hospitals.

In singleton pregnancies after in-vitro fertilization (IVF), increased rates of obstetric and perinatal complications have been reported. Studies that compared IVF twin pregnancies with spontaneously conceived twins have yielded conflicting results. We compared 96 IVF twin pregnancies to 96 controls after elaborate matching. The design of our study precluded matching by zygosity. The monozygosity rate was higher in the control group and this implies that beforehand the risk for a less favourable outcome in the control group was higher than in the IVF group. However, the average birthweight of the IVF children was less than that of children in the control group (P = 0.04). This was not due to more intrauterine growth retardation in the IVF group. The mean gestational age at birth was 5 days shorter in IVF than control pregnancies, and although this difference was not significant it might explain the lower birthweight in the IVF group. The discordance rate in the IVF group was significantly increased. We found no difference in perinatal mortality and morbidity. We conclude that this study provides further evidence for a different outcome of IVF twin pregnancies in comparison with spontaneously conceived twin pregnancies.

Influence of a highly purified senna extract on colonic epithelium.

BACKGROUND: Chronic use of sennoside laxatives often causes pseudomelanosis coli. A recent study suggested that pseudomelanosis coli is associated with an increased colorectal cancer risk. A single high dose of highly purified senna extract increased proliferation rate and reduced crypt length in the sigmoid colon compared to historical controls. AIMS: To evaluate in a controlled study the effects of highly purified senna extract on cell proliferation and crypt length in the entire colon and on p53 and bcl-2 expression. METHODS: Addition of a senna extract to colonic lavage was studied in 184 consecutive outpatients. From 32 randomised patients, 15 with sennosides (Sen), 17 without (NSen), biopsies were taken. Proliferative activity was studied in 4 areas of the colon, using 5-bromo-2'-deoxyuridine labelling and immunohistochemistry (labelling index, LI). Expression of p53 and bcl-2 in the sigmoid colon was determined immunohistochemically. RESULTS: Crypts were shorter in Sen than in NSen in the transverse and sigmoid colon. LI was higher in Sen than in NSen in the entire colon. No difference in p53 expression was seen. Bcl-2 expression was higher in both groups when crypts were shorter and/or proliferation was increased. CONCLUSION: Sennosides induce acute massive cell loss probably by apoptosis, causing shorter crypts, and increased cell proliferation and inhibition of apoptosis to restore cellularity. These effects may reflect the mechanism for the suggested cancer-promoting effect of chronic sennoside use.

[Pregnancy course and outcome in 2956 pregnancies after in-vitro fertilization in Netherlands]. / Beloop en uitkomst van 2956 zwangerschappen na in-vitrofertilisatie in Nederland.

OBJECTIVE: Description of the outcome of pregnancies after in vitro fertilisation (IVF) in Dutch IVF centers. DESIGN: Descriptive, retrospective. METHOD: Data were collected on IVF pregnancies in the period 1984-1992 from seven Dutch IVF centers. RESULTS: The study comprised 2956 pregnancies. Five centres provided data on 2133 ongoing and non-ongoing pregnancies. More than 25% ended in a spontaneous abortion (22.3%) or ectopic pregnancy (3.6%). From the seven centres there were data available on 2311 ongoing pregnancies. Of these, 30.8% were multiple; preterm delivery occurred in 29.2%. The birth weight of 40.6% of 3173 neonates was lower than 2500 g and that of 10.1% lower than 1500 g. A birth weight under the 10th percentile of the national reference curve was found in 16.7% and under the 2.3rd percentile in 4.3% of cases. Perinatal mortality was 31.3 pro mille. In 1588 singleton pregnancies preterm birth occurred in 15.6%; 41.3% of the singletons weighed less than 2500 g, of which 3.6% less than 1500 g while 12.3% had a birth weight below the 10th percentile. The results of our study are similar to those of other major studies in the literature and are unfavourable compared with to Dutch reference values. This is mainly due to the high proportion of multiple pregnancies. However, we found indications of a slight disturbance of pregnancy in IVF singleton and twin pregnancies.

AgNOR staining may reflect the growth potential of pilocytic astrocytomas.

The value of AgNOR staining as a tumor biological marker was tested in 26 children with pilocytic astrocytomas (20) and fibrillary astrocytomas (6). All patients were surgically treated and then followed up by periodic MRI or CT scans. Follow-up ranged from 8 to 84 months, with a mean of 44 months. AgNOR expression was determined by using semi-automated computer-assisted surface area measurements. AgNOR values ranged from 1.4 to 81.4 microm(2) per cell, with a mean of 26.6 and a median of 15.2. The median value was taken as a "cut-off" score separating two groups of patients with low and high AgNOR scores. Of the 13 patients in the low scoring group, 8 had total resections without recurrence, 3 had stable residual tumors, 1 had regressing residual tumor after irradiation and 1 had a recurrence 5 years after neuroradiologically complete resection of a fibrillary astrocytoma. In the group with high AgNOR scores only 2 patients had total resections without recurrence; 5 had stable residual tumors and 6 had residual tumors that showed progression, all within 1 year after surgery. Among the patients with classic juvenile pilocytic astrocytomas of the cerebellum 7 had residual tumor, which progressed in 2 patients, both of whom had high AgNOR scores. Among 7 patients with optic/hypothalamic tumors the 3 with rapidly progressing tumors all had very high AgNOR scores. The determination of AgNOR expression might be helpful in selection of patients with residual tumor after surgery, who may benefit from additional chemotherapy or (stereotactic) radiation therapy.

Hyperthermic isolated limb perfusion with tumor necrosis factor-alpha and melphalan in patients with locally advanced soft tissue sarcomas: treatment response and clinical outcome related to changes in proliferation and apoptosis.

Hyperthermic isolated limb perfusion with tumor necrosis factor-alpha and melphalan (HILP-TM) with or without IFN-gamma is a promising local treatment in patients with locally advanced extremity soft tissue sarcomas (STSs), with response rates of up to 84%. The mechanisms of the treatment response are poorly understood. Here, we determined the HILP-TM-induced changes in mitotic activity, proliferation, and apoptosis in 37 STSs; the additional effect of IFN-gamma; and the association of HILP-TM with treatment response and clinical outcome. On archival material, obtained before and 6-8 weeks after HILP-TM with (n = 15) or without (n = 22) IFN-gamma, the number of mitoses was counted, and the proliferation fraction was determined by immunohistological staining for the proliferation associated Ki-67 antigen (MIB1). Apoptosis was visualized by enzymatic detection of DNA fragmentation (terminal deoxynucleotidyl transferase-mediated nick end labeling method). Clinical and histological response, follow-up status, and survival were recorded. The number of mitoses dropped 57% and proliferation rate decreased with 40% after HILP-TM, whereas the amount of apoptosis after HILP-TM more than doubled as before HILP-TM. The addition of IFN-gamma to HILP-TM did not influence the changes in tumor parameters and did not affect treatment response. A better clinical response to HILP-TM was correlated with high mitotic activity and low amount of apoptosis in tumor samples before HILP-TM. Patients with highly proliferative STS before and after HILP-TM had a relatively poor prognosis. Furthermore, patients who developed distant metastases after HILP-TM had a relatively high number of dividing cells in the tumor remnants after treatment.

In squamous cell carcinoma of the vulva, overexpression of p53 is a late event and neither p53 nor mdm2 expression is a useful marker to predict lymph node metastases.

To offer more tailored treatment to individual patients with squamous cell carcinoma of the vulva, more accurate prediction of lymph node metastases is required. As p53 and mdm2 are genes known to be involved in the development of other tumours, we studied expression of p53 and mdm2 in carcinogenesis of squamous cell carcinoma of the vulva and their clinical relevance. Archival material of 141 T1 and T2 vulvar tumours were used. Of the 141 primary tumours, the corresponding 39 lymph node metastases (LNM) were studied, and in 90 cases the pre-existent epithelia adjacent to the tumour (EAT) and in 14 cases vulvar intraepithelial neoplasia adjacent to the tumour (VIN) was also investigated. Detection of p53 and mdm2 protein was immunohistochemically performed. Scoring categories were: negative (1); weakly positive (2); moderately to markedly positive (3); and markedly positive (4). Overexpression of p53 was seen in 56% of the LNM, 39% of the primary tumours, 21% of the VIN lesions and 0% in the group of EAT. No relation was found between overexpression of p53 in the primary tumour and LNM. Expression of mdm2 was seen in 14% of the primary tumours, of which four cases were marked positive. In the group of LNM no mdm2-positive staining was observed. In the group of EAT, 25% was mdm2-positive, of which six cases were marked positive. In the group of VIN, 36% showed moderate (score 3) mdm2 expression. No relation was found between expression of mdm2 and LNM. In squamous cell carcinoma, overexpression of p53 is a late event in carcinogenesis. Marked expression of mdm2 is rarely seen in vulvar carcinomas, indicating that aberrant p53 cannot induce mdm2 expression. LNM cannot be predicted by detection of these proteins.

Analysis of proliferation and apoptosis in brain gliomas: prognostic and clinical value.

With the introduction of new (immuno-)histochemical techniques it is now possible to assess rates of proliferation and apoptosis in brain gliomas using archival paraffin embedded material. As proliferation and apoptosis are related to tumour growth rate quantification of these processes has prognostic value and is related to tumour grading. In this study we assessed the proliferation rate by measuring the Ki-67 labelling index using the MIB-1 antibody (MIB-LI) and the apoptotic rate using the in situ labelling of DNA strand breaks with TUNEL (TUNEL-LI) in 315 supratentorial gliomas. MIB-LI and TUNEL-LI in astrocytomas (A) where significantly lower compared to anaplastic astrocytomas (AA), glioblastomas (GBM) and oligodendroglial tumours [oligodendrogliomas (O) and anaplastic oligodendrogliomas (AO)]. MIB-LI and TUNEL-LI were significantly lower in AA compared to GBM. In astrocytic tumours MIB-LI and TUNEL-LI appeared to be correlated. As the distinction between A and AA is of clinical value but can be difficult histomorphologically we analysed the prognostic value of MIB-LI and TUNEL-LI in gliomas with particular emphasis on A and AA. MIB-LI below 10% was of prognostic value in A and AA, O and AO but not in GBM on univariate survival analysis. TUNEL-LI was of no prognostic value. With multivariate survival analysis MIB-LI lost prognostic significance in O and AO. Astrocytomas with a gemistocytic component (AG) are similar to A with respect to survival and MIB-LI and TUNEL-LI. MIB-LI is of independent prognostic value in A and AA. Assessment of MIB-LI in A and AA can be used as an aid in distinguishing A and AA.

Clinical relevance of transforming growth factor alpha, epidermal growth factor receptor, p53, and Ki67 in colorectal liver metastases and corresponding primary tumors.

To determine whether the expression of transforming growth factor alpha (TGF-alpha), its receptor (epidermal growth factor receptor [EGFr]), p53 nuclear protein, and proliferation influences prognosis of patients with liver metastases, a study was performed in 45 liver metastases and 33 corresponding primary colorectal carcinomas in patients referred for liver surgery. The expression of TGF-alpha, EGFr, p53 nuclear protein, and proliferation rate was correlated with clinicopathological characteristics and survival after partial liver resection. In liver metastases, TGF-alpha expression was low in 42%, intermediate in 35%, and high in 23%. TGF-alpha expression was higher in liver metastases derived from lymph node-positive primary carcinomas, in synchronous and in irresectable liver metastases compared with those derived from lymph node-negative primary carcinomas, metachronous, and resectable liver metastases. Nuclear p53 expression was found in 83% of primary tumors and 71% of liver metastases. p53 expression did not correlate with the various clinicopathological characteristics. Ki67 expression was not associated with clinicopathological characteristics in primary and metastatic tumors. In the 38 patients in whom a partial liver resection was performed, median survival was 25 months in patients with a higher TGF-alpha expression in the metastasis than in the primary tumor and 60 months in patients with comparable or lower TGF-alpha expression in the metastasis than in the primary tumor (P = .036). Median survival after liver resection was 21 months in patients with p53-negative liver metastases and 58 months in patients with p53-positive metastases (P = .043). By multivariate analysis, p53 and EGFr expression on liver metastases were the best predictors of disease-free survival after partial liver resection, with relative risks of 2.38 and 3.33, respectively. In patients with colorectal liver metastases, referred for liver surgery, a higher TGF-alpha expression is associated with unfavorable tumor characteristics, whereas p53 and absence of EGFr expression is associated with a better survival after partial liver resection.

Epithelial cell proliferative activity of Barrett's esophagus: methodology and correlation with traditional cancer risk markers.

Barrett's esophagus (BE) is a premalignant condition, due to chronic gastroesophageal reflux. Effective antireflux therapy may diminish cancer risk. To evaluate this option an intermediate marker is needed. We developed a methodology for measurement of epithelial cell proliferative activity of Barrett's mucosa as an intermediate marker and correlated the activity with traditional cancer risk markers and other parameters. Fifty-six patients (21-74 years of age) with Barrett's esophagus and established acid gastroesophageal reflux were included. Biopsies were taken from Barrett's mucosa at 3-cm intervals. Reflux was measured by 24-hr pH-metry. Proliferative activity was determined using in vitro labeling with 5-bromodeoxyuridine and immunohistochemistry and was expressed as labeling index (LI). The length of BE correlated with erect acid reflux (P=0.002). LI in specialized columnar metaplasia was higher than in gastric metaplasia, especially in crypt epithelium (P < 0.05). Multiple regression analysis revealed independent positive correlations for surface LI with dysplasia (P=0.011), distance from the incisors (P=0.041), and crypt LI (P=0.000). Crypt LI showed an independent positive correlation with the length of BE (P=0.033) and type of metaplasia (P=0.007). In conclusion, epithelial cell proliferative activity of BE correlates with several known risk factors for cancer. Proliferative activity is an attractive intermediate marker to evaluate the effects of interventional measures to decrease cancer risk in Barrett's esophagus.

The proliferative potential of the pilocytic astrocytoma: the relation between MIB-1 labeling and clinical and neuro-radiological follow-up.

The proliferative potential of 39 pilocytic and 5 low grade astrocytomas was studied in relation to the Ki-67 activity as measured by the MIB-1 Labelings Index. The results were correlated to the biological behaviour of the tumor as measured by clinical and neuro-radiological (CT- or MRI-scans) follow-up of the patient. This study was undertaken to answer the question whether MIB-1 expression reflects differences in biological behaviour of these tumors, such as rapid progression of residual tumor or stable remaining tumor. MIB-1 LI values ranged from 0 to 19% in the group of pilocytic astrocytomas (mean 4.2%) and from 0 to 15% in the 5 low grade astrocytomas (mean 4,2%). All patients were operated and 23 of them had incomplete tumor resection as proven on postoperative neuro-imaging studies. Those 23 patients could be subdivided into two groups; one without progression of residual tumor during follow-up (n=12) and the other with tumor progression (n=11). mean MIB-1 LI in the group with 'quiescent' tumor tended to be lower than in the group with progressive tumor: 3,3% vs. 6,6%. Residual tumors which were negative for MIB-1 staining showed fewer progressions of residual tumor compared to those being positive for MIB-1 staining, however this difference was not significant (p=0, 15, Fisher exact test). Tumor samples of a second operation of the same patient had lower MIB-1 LI values than those of the samples taken at first operation. The proliferating potential seemed to be decreased after part of the tumor was resected. Pilocytic astrocytomas with a negative MIB-1 LI are unlikely to show progression of residual tumor after partial resection. MIB-1 staining might be an additional tool in determining the frequency and duration of follow-up and in making decisions regarding further treatment of a patient operated for a pilocytic astrocytoma with residual tumor.

Relationship between ovarian production of estrone, estradiol, testosterone, and androstenedione and the ovarian degree of stromal hyperplasia in postmenopausal women.

OBJECTIVE: To study the relationship between ovarian production of estrone (E ), estradiol (E2), testosterone (T), and androstenedione (A) and the ovarian degree of stromal hyperplasia in postmenopausal women. DESIGN: In 18 postmenopausal women, the ovarian vein hormone levels of E1, E2, T, and A were compared with the degree of ovarian stromal hyperplasia. The degree of stromal hyperplasia was assessed by histological analysis (group 1: atrophic ovaries, n = 8; group 2: slight stromal hyperplasia, n = 8; group 3: moderate or severe stromal hyperplasia, n = 2). RESULTS: The ovarian levels of E1 and E2 did not correlate with the ovarian degree of stromal hyperplasia. The ovarian levels of A in group 3 were significantly higher than those in groups 1 and 2 (p < 0.02 and p < 0.01, respectively). The ovarian levels of T in group 3 were significantly higher than those in group 1 (p < 0.01) but did not differ significantly from those in group 2. CONCLUSIONS: The amount of stromal hyperplasia in postmenopausal ovaries is correlated with the ovarian vein levels of A and T. Morphological characteristics of the postmenopausal ovary determine the local (pelvic) endocrine status and may play a role in the etiology of hormone-dependent diseases of the internal genitals.

Proliferative activity in human brain tumors: comparison of histopathology and L-[1-(11)C]tyrosine PET.

UNLABELLED: To validate the protein synthesis rate (PSR) measured in human brain tumors using L-[1-(11)C]tyrosine (TYR) PET, the PSR was compared to histopathological parameters that reflect proliferation and protein synthesis. METHODS: We studied 20 patients who had a brain biopsy and who also underwent a PET study with TYR. Paraffin sections were stained with the monoclonal antibody MIB 1, targeted against the core antigen Ki-67, and nucleolar organizer regions (NORs) were measured as argyrophilic NORs (AgNORs). The TYR uptake was measured by PET, and with a kinetic model, the PSR was determined. RESULTS: PSR (nmol/ml/min) ranged from 0.44 to 1.99 (mean, 0.97), Ki-67 labeling indices (%) ranged from 0.9 to 33.5 (mean, 9.5) and AgNOR area (mm2/cm2) ranged from 0.13 to 0.85. No relationship was found between PSR and Ki-67 labeling index or AgNOR area. CONCLUSION: It seems that the PSR and proliferation, as measured by Ki-67, are independent processes. The role of the PSR is uncertain, but it is likely that it can be seen as a marker for the homeostasis of the cell.

Trivariate flow cytometric analysis of paraffin-embedded lung cancer specimens: application of cytokeratin subtype specific antibodies to distinguish between differentiation pathways.

The aim of the present study was to investigate whether trivariate FCM analysis, for the simultaneous detection of two different CK subtypes in combination with DNA content, can be applied to paraffin embedded samples of different types of non-small cell lung cancer in order to evaluate the cell cycle of individual sublines. Single cell suspensions were prepared from 50 microm thick paraffin sections of 22 lung carcinomas by pepsin digestion and immunostained with CK-antibodies which were chosen to distinguish glandular differentiation (adenocarcinomas) and squamous differentiation. There was a good correlation between the immunocytochemical results of the different CK antibodies in tissue sections and in the corresponding single cell suspensions. Gating for CK-positivity revealed a higher S-phase fraction as compared to the ungated cell population. The tumor cells in adenocarcinoma cases were specifically recognized by CK7 antibodies, while well-differentiated squamous cell carcinomas were specifically stained for CK14 and/or CK17. In poorly differentiated squamous cell carcinomas simultaneous expression of CK7 and CK17 was detected in a subpopulation of the tumor cells, next to cells positive for CK7 or CK17 alone. The trivariate FCM analysis allowed the separate estimation of ploidy status and cell cycle parameters in the three different cell populations of these, apparently (phenotypically) heterogeneous, malignancies.

Simultaneous epstein barr virus and cytomegalovirus infection accompanied by leiomyomatous change in a well-differentiated liposarcoma in a patient with long-term corticosteroid treatment.

Patient. A 59-year-old woman presented with a large tumour of the abdominal wall. She had been taking corticosteroids for severe chronic obstructive pulmonary disease for 15 years. On CT scan the tumour had the characteristics of lipomatous tissue with a dense core.Results. Histology showed a well-differentiated liposarcoma with a core of benign fibroleiomyomatous differentiation. Within the core, a third component was observed, characterized by more pleomorphism and the presence of an inflammatory infiltrate. In this component, immunoperoxidase stains and in situ hybridization demonstrated cytomegalovirus (CMV) and Epstein Barr virus (EBV) infection in large and small cells, respectively.Discussion. Long-term corticosteroid use for pulmonary disease may extend the list of immunosuppressed states associated with the development of leiomyomatous tumours with EBV infection, previously described in AIDS patients and liver transplant recipients. The role of CMV is uncertain.

Detection of HPV-16 DNA by PCR in histologically cancer free lymph nodes from patients with cervical cancer.

The prognostic value of detection of human papillomavirus (HPV) type 16 DNA in histologically cancer free lymph nodes was assessed in left obturator lymph nodes from cervical cancer patients with HPV-16 positive primary tumours. HPV-16 DNA was detected by polymerase chain reaction in 12 of 35 patients with histologically cancer free lymph nodes. Of these 12 patients, only one developed a recurrence, suggesting HPV-16 DNA detection in cancer free lymph nodes has no prognostic value.

Androgen receptor content in human endometrium.

Human endometrium changes morphologically and biochemically during the various phases of the menstrual cycle, influenced by not only estrogens and progesterone, but probably also by androgens. The purpose of this study was to investigate the androgen receptor (AR) content in human endometrium and myometrium and its significance. AR immunocytochemistry was performed on 30 paraffin-embedded uterine sections of pre-menopausal women who were scheduled for hysterectomy because of benign gynaecologic abnormalities. AR receptor content was seen in all cell types of the human endometrium and myometrium and was cyclic dependent. AR immunostaining of stromal and smooth muscle cells was more profound than AR staining of glandular cells. There was more AR expression in the proliferative phases than in the secretory phases: in the late secretory phase there was no immunostaining in any of the cell types. AR expression is primarily under androgenic control. Inside the cell testosterone may be 5 alpha-reduced to dihydrotestosterone (DHT). Due to local competition between testosterone and the excess of progesterone in the secretory phase for the same iso-enzyme 5 alpha-reductase, the level of DHT will be diminished in the late secretory phase. If AR synthesis in endometrium would be DHT dependent, the virtual disappearance of DHT would explain the lack of AR expression in the late secretory phase. Whether the cyclic pattern of AR expression is merely an epiphenomenon to progesterone production, or whether androgens play a causal role in the cyclic modulation of endometrium is subject to further research.