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A Gompel

Publications and source records attributed to A Gompel.

At least 19 recordsLinked to original sources
PubMed2002

Comparative activity of pulsed or continuous estradiol exposure on gene expression and proliferation of normal and tumoral human breast cells.

Intranasal administration of hormone replacement therapy presents an original plasma kinetic profile with transient estrogen levels giving rise to the concept of pulsed therapy. To further understand the molecular effects of this new therapy, we have compared the effects of pulsed and continuous estradiol treatments on two critical aspects of estradiol action: gene expression and cell proliferation. Cells were stimulated with estradiol as 1-h pulsed or 24-h continuous treatments at concentrations such that the 24-h exposure (concentration x time) was identical in both conditions. In MCF7 cells, the transcriptional activity of estrogen receptors (ER) on a transiently transfected responsive estrogen response element-luciferase reporter construct was shown to be drastically (approximately 10-fold) and similarly stimulated after both treatments. Moreover, the increased mRNA expression of three representative estradiol-sensitive genes (pS2, cathepsin D, progesterone receptor), evaluated by Northern blot, was identical after 1-h pulse with 7 nM estradiol or continuous treatment with 0.29 nM estradiol with the same kinetic profile over 48 h. Proliferation was quantified by a histomorphometric method on primary cultures of human normal breast cells from reduction mammoplasties and using a fluorescence DNA assay in six human breast cancer cell lines which were ER positive or negative. After a 7-day treatment period, estradiol had no effect on the proliferation of the three ER negative cell lines (BT20, MDA MB231, SK BR3) but significantly stimulated the proliferation of the normal cells and of the three tumoral hormone-sensitive cell lines (MCF7, T47D, ZR 75-1); both hormone treatments producing the same increases in cell growth. In conclusion, we have shown that the genomic or proliferative effects of estradiol were identical with pulsed or continuous treatments, thus indicating that estrogenic effects are not strictly related to concentrations but rather to total hormone exposure.

Administration, Intranasal↗
PubMed2001

Therapeutic value and long-term safety of pulsed estrogen therapy.

OBJECTIVES: To demonstrate equivalent efficacy for menopausal symptoms between Aerodiol nasal spray and reference oral estradiol therapy, and to investigate the endometrial safety and tolerability of Aerodiol in the long term. METHODS: The efficacy of Aerodiol 300 microg, once daily, was compared with oral estradiol 2 mg/day in a randomized, double-blind trial. A statistical test of noninferiority was performed on the mean absolute Kupperman index (KI) obtained after 14 and 23 weeks of the two treatments. Long-term safety was assessed in a 1-year open-label study. The initial Aerodiol dose was 300 microg/day, and was adjusted if required. Endometrial biopsies were obtained at inclusion and at the end of the trial and examined independently by two pathologists. RESULTS: In the equivalence trial, the KI improved similarly in the Aerodiol group (n=317) and the oral estradiol group (n=342). Aerodiol was shown statistically to be at least as effective as oral therapy (P<0.001), but the incidences of mastalgia and withdrawal bleeding were significantly lower in the Aerodiol group (P<0.01 and P<0.001, respectively). In the long-term safety trial (n=408), the rate of Aerodiol treatment continuation at 12 months was 85%, and there was no incidence of endometrial hyperplasia or cancer. Aerodiol dose adaptation was performed by 29% of women. CONCLUSIONS: Aerodiol was shown to have equivalent efficacy to reference oral estradiol therapy, but with better gynaecological acceptability. The endometrial safety of Aerodiol was confirmed in the long term, and the ability to adjust the dosage easily was of benefit to a substantial proportion of women.

Administration, Intranasal↗
PubMed2001

Resistance to induced apoptosis in the human neuroblastoma cell line SK-N-SH in relation to neuronal differentiation. Role of Bcl-2 protein family.

Much evidence suggests that apoptosis plays a crucial role in cell population homeostasis that depends on the expression of various genes implicated in the control of cell life and death. The sensitivity of human neuroblastoma cells SK-N-SH to undergo apoptosis induced by thapsigargin was examined. SK-N-SH were previously differentiated into neuronal cells by treatments with retinoic acid (RA), 4 beta-phorbol 12-myristate 13-acetate (PMA) which increases protein kinase C (PKC) activity, and staurosporine which decreases PKC activity. Neuronal differentiation was evaluated by gamma-enolase, microtubule associated protein 2 (MAP2) and synaptophysin immunocytochemistry. The sensitivity of the cells to thapsigargin-induced apoptosis was evaluated by cell viability and nuclear fragmentation (Hoechst 33258) and compared with pro-(Bcl-2, Bcl-x(L)) and anti-apoptotic (Bax, Bak) protein expression of the Bcl-2 family. Cells treated with RA and PMA were more resistant to apoptosis than controls. Conversely, the cells treated with staurosporine were more susceptible to apoptosis. In parallel with morphological modifications, the expression of inhibitors and activators of apoptosis was directly dependent upon the differentiating agent used. Bcl-2 expression was strongly increased by PMA and drastically decreased by staurosporine as was Bcl-x(L) expression. Bax and Bak expression were not significantly modified. These results demonstrate that drugs that modulate PKC activity may induce a modification of Bcl-2 expression as well as resistance to the apoptotic process. Furthermore, the expression of Bcl-2 was reduced by toxin B from Clostridium difficile and, to a lesser extent, by wortmannin suggesting a role of small G-protein RhoA and PtdIns3 kinase in the control of Bcl-2 expression. Our data demonstrate a relationship between the continuous activation of PKC, the expression of Bcl-2 protein family and the resistance of differentiated SK-N-SH to apoptosis.

Androstadienes↗
PubMed2000

Endometrial safety and tolerability of AERODIOL(R) (intranasal estradiol) for 1 year.

OBJECTIVE: the purpose of this study was to assess the endometrial safety and patient acceptability of a pulsed estrogen therapy provided by S21400 (intranasal 17 beta-estradiol) in the treatment of postmenopausal symptoms. DESIGN: postmenopausal women (n=408) entered an open-label, community based, multicentre trial. Patients received S21400 plus sequential (>90% of patients) or continuous progestogen. Treatment was initiated with a standard daily dose of 300 microg but dose adaptation was possible every 3 months from 150 to 600 microg daily. Endometrial biopsies were performed at entry and at 12 months, and bleeding patterns were recorded at 3-monthly intervals throughout the trial. RESULTS: 71% of patients received 300 microg per day S21400 throughout the study, 3% had their dose decreased, 19% had their dose increased and 7% had their dose both decreased and increased. Three hundred and eleven biopsies were obtained after 12 months of treatment, there were no cases of endometrial hyperplasia. The 95% confidence interval [CI] for the rate of incidence was 0-1.2%. Cyclical bleeding occurred in 82% of sequential treatment cycles. Unexpected bleeding occurred in 5% of the treatment cycles. Presence of unexpected bleeding varied according to the treatment regimen, 15 and 4% of the cycles with combined continuous and sequential regimen, respectively. Unexpected bleeding was mostly spotting. Nasal treatment was well accepted. Nasal symptoms (itching sensation, rhinorrhea and sneezing) were mostly mild in intensity and they led to treatment withdrawal in approximately 3% of patients. The rate of treatment continuation was 85% at 1 year. CONCLUSIONS: S21400, in combination with continuous or sequential progestogen, exhibits good endometrial safety and patient acceptability in postmenopausal women.

Administration, Intranasal↗
PubMed2000

[Hemoperitoneum of ovarian origin complicating antivitamin K treatment].

INTRODUCTION: Ovarian hemorrhage with hemoperitoneum is a rare but serious complication of ovulation related to rupture of either the corpus luteum or functional cyst. It is due to treatment using oral indirect anticoagulant and specifically affects young women. CURRENT KNOWLEDGE AND KEY POINTS: We review cases that were reported since the initial description by Weseley in 1957. The main indications for oral indirect anticoagulant are thrombophlebitis and valvular cardiac prosthesis. Pelvic pain with peritoneal irritation is the most common symptom in more than one third of the patients. An initial collapse is reported in 22% of the cases. Surgery is the main treatment. Mortality is 3% and recurrences occur in nearly 25% of the patients. FUTURE PROSPECTS AND PROJECTS: Potential ovarian hemorrhage should be investigated when a woman taking oral indirect anticoagulant develops acute abdominal pain. Surgery should be conservative and whenever possible, should include celioscopy. Systematic ovarian blockade should be discussed in women taking long-term oral indirect anticoagulant.

Administration, Oral↗
PubMed2000

Tibolone actions on normal and breast cancer cells.

Tibolone and its main derivatives were studied in an original model of cultures of normal human epithelial breast (HBE) cells on proliferation, differentiation and apoptosis, the three mechanisms responsible for breast homeostasis. Tibolone and its Delta4 isomer were antiproliferative, both in the absence and presence of oestradiol (E2). The oestrogenic 3alpha and 3beta hydroxy derivatives did not display any mitogenic activities in HBE cells. Moreover, at 1 microM, they were antiproliferative. Tibolone and its Delta isomer increased the 17beta hydroxysteroid dehydrogenase activity similarly to that observed with progestins [1]. Apoptosis was increased in HBE cells to a similar range as with the pure pregnane progestin, Org2058. We also studied the extent of apoptosis in hormone-dependent breast cancer cell lines. Tibolone and its Delta4 isomer also increased apoptosis, especially in ZR75-1 cells containing progesterone and androgen receptors [2]. We could demonstrate that these pro-apoptotic actions of tibolone and its Delta4 isomer were mediated at least partially through the bcl-2-family of proteins. Moreover, the antiproliferative and pro-apoptotic activities of tibolone, as well as Org2058, were mediated by increasing catalase activities in breast cancer cells. Thus, in breast cells, tibolone slows down the proliferation rate, increases differentiation and apoptosis. These actions seem to be optimal on breast tissue.

Antineoplastic Agents, Hormonal↗
PubMed2000

[Hormone replacement therapy after endometrial or ovarian cancer].

Use of hormonal replacement therapy after treatment of ovarian or endometrial cancer remains a matter of debate. Novel adjuvant therapies tend to increase the survival of these patients, who are exposed to risk factors of hormonal deficiency subsequent to primary therapy. Therefore, the aims of the present review of literature was to analyse epidemiologic and clinical parameters on behalf on hormonal replacement therapy in this population.

Endometrial Neoplasms↗
PubMed2000

[Bladder endometriosis. Apropos of 4 cases and review of the literature].

The aim of our study is to evaluate the diagnostic and therapeutic attitude toward endometriosis of the bladder. We have analysed four observations treated in the gynecologic service of Hotel-Dieu in Paris between January 1989 and January 1998, which represents 1.3% of all endometriosis operated during this period. Every patient underwent echography, RMN, UIV and cystoscopy. In all for cases a surgical treatment by laparotomy was realised. The choice of this way is explained by the multiple localisations of endometriosis in three cases and the impossibility of a coelioscopic treatment in the forth. The anatomopathologic exam found endometriosis in all of the cases.

Adult↗
PubMed1999

Massive ovarian haemorrhage complicating oral anticoagulation in the antiphospholipid syndrome: a report of three cases.

We report three cases of severe haemorrhagic rupture of luteal ovarian cyst requiring surgical haemostasis in young women treated with long-term oral anticoagulation for antiphospholipid syndrome (APS) who used no contraception. At the time of bleeding, the international normalized ratios were 3.78, 4.24, and 7.11. Anticoagulation was resumed post-operatively, in association with antigonadotropic progestins to induce ovulatory suppression. A systematic use of these progestins should probably be discussed in young women receiving long-term warfarin for APS. Ovarian haemorrhage must be considered when such patients develop acute abdominal pain.

Administration, Oral↗
PubMed1999

Evaluation of gonadal function in 107 intersex patients by means of serum antimüllerian hormone measurement.

Fetal male sexual differentiation is driven by two testicular hormones: testosterone (synthesized by interstitial Leydig cells) and antimüllerian hormone (AMH; produced by Sertoli cells present in the seminiferous tubules). Intersex states result either from gonadal dysgenesis, in which both Leydig and Sertoli cell populations are affected, or from impaired secretion or action of either testosterone or AMH. Until now, only Leydig cell function has been assessed in children with ambiguous genitalia, by means of testosterone assay. To determine whether serum AMH would help in the diagnosis of intersex conditions, we assayed serum AMH levels in 107 patients with ambiguous genitalia of various etiologies. In XY patients, AMH was low when the intersex condition was caused by abnormal testicular determination (including pure and partial gonadal dysgenesis) but was normal or elevated in patients with impaired testosterone secretion, whereas serum testosterone was low in both groups. AMH was also elevated during the first year of life and at puberty in intersex states caused by androgen insensitivity. In 46,XX patients with a normal male phenotype or ambiguous genitalia, in whom the diagnosis of female pseudohermaphroditism had been excluded, serum AMH levels higher than 75 pmol/L were indicative of the presence of testicular tissue and correlated with the mass of functional testicular parenchyma. In conclusion, serum AMH determination is a powerful tool to assess Sertoli cell function in children with intersex states, and it helps to distinguish between defects of male sexual differentiation caused by abnormal testicular determination and those resulting from isolated impairment of testosterone secretion or action.

Adult↗
PubMed1999

[Action of SERM and SAS (tibolone) on breast tissue].

SERMs are developed in HRT in order to provide the beneficial effects of estradiol on bone and the cardiovascular system. SERMs are antiestrogens and their properties depend upon the pharmacological class they belong to. Tibolone is a progestin with mixed properties. Our studies on breast cells in vitro demonstrated that it behaves as a progestin in these cells. The clinical data obtained with these various therapies on breast are presented.

Antineoplastic Agents, Hormonal↗
PubMed1998

Can we advise ovulation induction in patients with SLE?

The prognosis of systemic lupus erythematosus (SLE) has greatly improved during the last two decades, now allowing most patients to have a very long survival including a satisfactory quality of life. Initially considered contraindicated in SLE due to its overwhelming risks, pregnancy is nowadays allowed in a majority of patients, and fair results are usually obtained under appropriate management (1-3). Consequently, patients thought to have infertility ask the question of a possible therapy, i.e. ovulation induction (OI) associated or not with in vitro fertilization (IVF). Considering the importance of estrogens in the pathogenesis of the disease, the use of such procedures raise several questions in SLE. Though data remain to date extremely scarce, the theoretical and practical aspects of OI in SLE will be briefly reviewed here.

Adult↗