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Background/aims: The synthetic estrogen 17alpha-ethinyl estradiol (EE), a potent tumor promoter in rat liver, stimulates growth during short-term treatment but inhibits hepatocyte proliferation upon prolonged treatment. To identify the molecular targets of the mitoinhibitory effect of EE, the expression of proteins regulating G(1)- and S-progression were analyzed during the first cell cycle in EE-treated female Wistar rats., Methods: Long-term (60 days) EE treatment. Immunohistochemical staining for proliferation cell nuclear antigen (PCNA) to detect cells in S phase and quantification of mitosis. Western blot to monitor protein expression. Cdk2 kinase assay to examine histone H1 phosphorylation., Results: EE reduced the number of cells in S phase and mitosis by about 70%. Cyclin D1 and D3 were unaffected, while cdk4 was moderately decreased. Cyclin E and cdk2 were markedly decreased with concomitant marked reduction of cdk2 kinase activity. EE also decreased cyclin A and increased G1 levels of p53 and p21., Conclusions: EE causes a cell cycle block before S-phase. The reduction of the cdk2 kinase activity, essential for G1/S-transition, might be involved in the cell cycle block. Also, EE treatment results in p53 activation and upregulation of the cdk inhibitor p21 that might contribute to the G1 arrest.

This paper presents the correlative changes of cancellous bone histomorphometry, biomechanical property and bone mineral contents of lumbar vertebrae in ovariectomized rats. Forty eight 10.5-month-old female SD rats were randomized to six groups: 1) Basal: at 10.5 mon. of age; 2) sham-1: sham-operated at 13 mon. of age; 3) OVX-1: ovariectomized at 13 mon. of age; 4) sham-2: sham-operated at 16 mon. of age; 5) OVX-2: ovariectomized at 16 mon. of age; and 6) OVX-2 + EE: ovariectomized and treated with 17 alpha-ethynylestradiol (100 micrograms.kg-1.d-1) starting at 13 mon. of age for 12 weeks. Double in vivo fluorochrome labeling was administered to all rats. At the end-point of study, the undecalcified longitudinal fourth lumbar vertebra (LV4) sections were cut and stained with Goldner's Trichrome for bone histomorphometric analyses. The mechanical properties of the compact fifth lumbar vertebra body (LV5) were measured with compression test, the LV5 bodies then were dried constantly with high temperature and digested with acid for testing of bone mineral content. A trend in trabecular bone volume (BV/TV), trabecular thickness (Tb.Th) of LV4, bone break load, break stress, elastic moduli and bone calcium content of LV5 to increase with the increase of age was revealed in the intact rats, but the highest value was at 13 mon. of age. A positive correlation was seen between histomophormetry and bone bio-mechanical properties in the intact rats. Compared with the data from the sham-operated rats, the BV/TV and Tb. Th significantly decreased and bone turnover rate significantly increased in OVX rats at 10 weeks, and the above parameters further decreased 22 weeks post OVX. Correspondingly, the bone break load, break stress, elastic moduli and bone calcium content significantly decreased with the increase of time post OVX was compared with those of sham-operated rats. A positive correlation between histomophormetry and bone biomechanical properties was also observed in OVX rats (r = 0.399, P = 0.018). Bone histomorphometry is good for predicting early physiological and pathological changes and bone biomechanical properties are good parameters for predicting corresponding function of bone such as fracture. Both of them are useful and needful in the animal studies on osteoporosis and related pharmacodynamic observations on new drugs.

Sixty-four patients took part in a cohort study measuring the efficacy of daily hormonal therapy in diminishing intestinal bleeding from small bowel angiodysplasia. Thirty patients received 5-10 mg norethynodrel either with mestranol, 0.075-0.15 mg (24 patients) or with conjugated estrogens, 0.625 mg (six patients). The cohort group consisted of 34 patients who either refused hormonal therapy (six patients) or were diagnosed early in our experience, before the resurgence of hormonal therapy (28 patients). Mean follow-up was 15.6 months (range 2-31 months) for the treated group and 13.4 months (range 1-23 months) for the untreated group. In addition, the change in monthly transfusion requirement with therapy was analyzed ("within group" analysis). Fifty percent (15 of 30) of the treated group required no further transfusion during therapy, while 44% (15 of 34) of the untreated group required no further therapy (not significant). During therapy, the mean monthly transfusion requirement of packed red blood cells in the treated group was not significantly different from that found before therapy (1.5 vs. 2.2 units, NS) or from that of the control group (1.5 vs. 1.6 units, NS). The findings do not support the use of hormonal therapy for bleeding from small intestinal angiodysplasia.

Vicarious menstruation represents cyclical bleeding in extragenital organs during a normal menstrual cycle. We present an unusual case of ocular vicarious menstruation (bloody tears) in a 17-year-old girl. The indications and treatment of this rare disorder are discussed.

Fifty patients with endometriosis were treated with hormones: 27 with danazol and 23 with Enavid (mestranol 75 micrograms and norethynodrel 5 mg). Side effects were more common and potentially more serious in the group treated with Enavid. Fewer women completed treatment with Enavid and their physical signs showed little improvement. Danazol was better tolerated and the results of treatment, as judged by improvement of symptoms or signs and in future fertility rates, were superior to those recorded in the Enavid treated group. Patients with large endometriotic cysts or severe fibrosis did not benefit from medical treatment. Danazol treatment appeared helpful for women who had mild or moderate endometriotic disease. It may be used alone or as a complimentary treatment after conservative surgical operations.

Male and female nonarteriosclerotic (virgin) and arteriosclerotic (breeder) Sprague-Dawley rats were subjected to acute myocardial infarction with isoprenaline. When myocardial necrosis was most intense, animals were given cortisone (high and low doses), Dianabol, or Enovid. Animals receiving large doses of cortisone manifested the best survival rate during the early stages of myocardial infarction. Although their serum enzyme levels were least elevated and their hearts showed tha least amount of damage, these animals had undergone the most intense body weight loss and began to die suddenly during the later stages of the experiment. These animals also manifested hyperlipidaemia, hyperglycaemia, septicaemia, severe disuse atrophy of their adrenal glands, and reduced Cmpd. B production. Animals treated with low doses of cortisone or with the anabolic and androgenic steroid, Dianabol, manifested none of the myocardial pretective effects of the larger dose of cortisone. These animals displayed a high incidence of left ventricular aneurysm formation concomitant with extensive cartilaginous metaplasia within the aneurysmal sites. Treatment with the contraceptive drug, Enovid, caused body weight loss, hyperlipidaemia, hyperglycaemia, gonadal atrophy and reduction of Cmpd. B production. Although the high dose of cortisone exercised definite salutary effects during early myocardial infarction, chronic treatment led to adrenal disuse atrophy and hypoadrenocorticism associated with sudden death during the later stages of myocardial repair. These findings indicate that proper adjustment of the dose and chronicity of corticosteroids used for treating the crisis of acute myocardial infarction must be made in order to provide effective protection against untoward pathophysiological conditions, acceleration of myocardial repair, but without suppression of adrenal function.

Hormonal therapy has long been the mainstay of the medical management of endometriosis. However, there is considerable confusion regarding the appropriate application of hormones in the treatment of endometriosis. This article critically reviews the current status of the steroidal therapy of endometriosis.

Recurrent gastrointestinal bleeding ceased after the institution of estrogen-progesterone therapy in a patient with gastrointestinal angiodysplasia without chronic renal failure. The patient did have aortic stenosis and mitral insufficiency murmurs. A therapeutic trial of conjugated estrogen should be considered in patients with recurrent gastrointestinal bleeding secondary to gastrointestinal angiodysplasia after the use of therapeutic endoscopy and/or surgery.

We describe a new method for successful management of epistaxis in patients with hereditary hemorrhagic telangiectasias. By so doing, even pulmonary arteriovenous fistulas and gastrointestinal hemorrhages can be successfully managed. During a four year period, 14 patients were treated with an oral contraceptive preparation which combined a reduced dosage of estrogen and progesterone. With this therapy, 11 patients stopped bleeding while 3 responded with significant improvement. We believe that this effect on bleeding by the hormone therapy is a sign of an abnormal increase of specific hormone requirements in patients with Osler's disease.

The combination of a progestogen and an estrogen (Enovid, Enovid E) has been used successfully in the management of nine patients with hereditary hemorrhagic telangiectasia (HHT) and severe epistaxis: Such therapy was instituted when epistaxis was severe and only after other therapeutic measures had failed. Seven of our patients required the 5-mg tablet (Enovid) to achieve a satisfactory clinical result; two patients received the 2.5-mg preparation (Enovid E). The eight women received cyclic therapy; the man received therapy without interruption. Because of the possibility of serious adverse effects from the drugs, it is required that each patient receive a complete medical evaluation prior to therapy and at frequent intervals while receiving therapy. Enovid therapy for HHT is not recommended for the patient with mild bleeding that can be controlled by conventional therapy.

In a comparison of danazol, and mestranol with norethynodrel (Enavid, Searle) in the treatment of endometriosis danazol was shown to be superior. Danazol is however relatively ineffective when large tumours or extensive adhesions are present and such patients will usually need a surgical operation. Women who have completed their families and who have severe symptoms will be better treated by hysterectomy. Treatment with danazol is indicated for young women with mild or moderate endometriosis. Danazol treatment may also be given postoperatively after conservative operations.

Eight patients with hereditary hemorrhagic telangiectasia and severe epistaxis were treated with norethynodrel with mestranol (Enovid). Biopsy specimens of typical lesions from two patients were taken for electron microscopy before and after several months of therapy. Characteristic endothelial cell damage and nectosis were noted in the dilated venules of patients before treatment but not after. Unlined channels of blood were found in connective tissue before treatment but not after. These are thought to arise from leaks in the affected venules, and it is suggested that later indothelial ingrowth gives rise to the propagation of lesions that are known to develop with age. Reduplicated basal laminae and regenerating endothelial cells were found both before and after treatment.

Gastrointestinal telangiectasias cause hemorrhage in patients with chronic renal failure. Therapies using vasoconstrictors, endoscopic application of heat, and surgery have had limited efficacy. Because several reports have suggested that estrogen or estrogen-progesterone therapy may control mucosal bleeding from telangiectasias in patients with hereditary hemorrhagic telangiectasia, we treated seven patients with chronic renal failure and bleeding gastrointestinal telangiectasias with systemic estrogen or estrogen-progesterone in an uncontrolled trial. Bleeding ceased in all patients. Blood transfusion requirements decreased from a mean of 1.2 U/month before treatment to 0.21 U/month after treatment. No significant side effects were noted. Results of this trial indicate the need for controlled investigations of this type of hormonal therapy.

An 11-year-old premenarchial girl who demonstrated the clinical and biochemical abnormalities of the Stein-Leventhal syndrome is reported. Although the concentration of total circulating testosterone was within normal limits, levels of free testosterone and testosterone-estradiol-binding globulin (12.9 to 22.7 pg/ml and 7.9 to 11 X 10(-9) moles/liter, respectively) were markedly different from those of prepubertal girls (1.1 +/- 0.9 pg/ml and 102 +/- 27 X 10%-9) moles/liter, mean +/- 1 SD) and normal women (4.3 +/- 1.2 pg/ml and 82 +/- 30 X 10(-9) moles/liter). Luteinizing hormone but not follicle-stimulating hormone concentrations were increased. In the absence of abnormal adrenal steroid excretion or response to dexamethasone suppression and with a clear biochemical response to oral contraceptives (decreased levels of luteinizing hormone and free testosterone and increased concentrations of testosterone-estradiol-binding globulin), this patient closely resembles older individuals with the Stein-Leventhal syndrome. Therefore, the measurement of testosterone-estradiol-binding globulin and free testosterone may be useful in the laboratory evaluation of any adolescent girl in whom no other cause for hirsutism can be identified.

Described is a patient with severe iron deficiency anemia and chronic gastrointestinal bleeding caused by hereditary hemorrhagic telangiectasia who was successfully treated with a combination of estrogen and progestogen.

A 27-year-old woman with right-sided cyclic sciatica and stiffness of the right hip joint, unresponsive to orthopaedic measures, is presented. An exploratory laparotomy revealed pelvic endometriosis. On oestrogen suppression therapy, she has been symptom-free for eleven months.

A case of sacral chordoma causing chronic, persistant low-back pain for 5 years is reported. This tumor was palpable on pelvic and rectal examination in the presacral area. Early excision is the treatment of choice for this slow growing tumor of primitive notochordal origin. Diagnosis is often late and incomplete surgical excision leads to local recurrence and eventual death. Knowledge of the existence of this rare condition, together with careful pelvic and rectal examination, are the importnat keys to diagnosis and possible curative treatment.