Psychosocial experiences in women facing fertility problems--a comparative survey.

In a survey involving 281 patients awaiting assisted reproduction treatment at five centres in three countries, and 289 population controls, we investigated whether the patients had experienced more negative emotional feelings and negative emotional impact during periods when they were attempting to conceive as compared with the controls, and whether there was any difference in their well-being at the time of consultation. The study was performed in the context of currently divergent views as to the burden of fertility problems. The survey was carried out using questionnaires of the self-administration type. Women with fertility problems did in fact consistently report a higher prevalence of negative emotions than the controls with reference to the periods during which they had been trying to conceive. Patients reported more changes in interpartner relationships (either negative or positive). Sexuality was negatively affected among the patients. At the time of consultation, the patients had less favourable scores than the controls on scales for depressed mood, memory/concentration, anxiety and fears, as well as for self-perceived attractiveness. One in four (24.9%) of the patients had scores indicating depressive disorders as compared with only 6.8% of the controls. Current well-being was even more markedly affected in patients with previous unsuccessful in-vitro fertilization (IVF) experience. The 'infertility' life event was perceived as severe by both patients and controls. Both prior to consultation and during diagnosis and treatment, women with fertility problems had a higher prevalence of reported negative psycho-emotional experiences than women without fertility problems.

The metabolism of mianserin in women, rabbits, and rats: identification of the major urinary metabolites.

The biotransformation of orally administered 3H-mianserin was investigated in female human subjects, rabbits, and rats by identification of the major urinary metabolites. Three days after dosing, the urinary excretion of radioactivity was 53% in women, 36% in rats, and 80% in rabbits. In the women's urine, 15% of the administered dose was excreted in the form of mianserin (conjugated plus nonconjugated); in the animal species this quantity was 1-2%. Mianserin was predominantly metabolized to 8-hydroxy analogs in all species; in rats, 8-hydroxydesmethylmianserin was the principal metabolite. Demethylation was an important metabolic pathway in the animal species, but not in women. Novel N-formyl compounds were detected in the urine of both animal species, but the possibility that these were artifacts formed during extraction with chloroform cannot be ruled out. Trace amounts of two compounds in which the piperazine moiety of mianserin was absent, 11H-dibenz[b,e]azepine and 11 H-dibenz[b,e]azepine-2-ol, were identified in the urine of rabbits and rats, respectively.

Metabolism of a new synthetic progestagen, Org 2969, in female volunteers. The distribution and excretion of radioactivity after an oral dose of the labelled drug.

The metabolism of a new synthetic progestagen, Org 2969 was studied in 4 healthy female volunteers. During the first part of the study (Phase I), the volunteers ingested 50 microgram (about 0.1 mCi) of [16-3H5Org 2969 together with 50 microgram of ethinyloestradiol as a single dose. During the second part of the study (Phase II), a 10-day pre-treatment with the same dosage of non-radioactive compound preceded the administration of the radioactive steroid. A peak level of total radioactivity, representing 3.16-5.02% of the dose given/l of serum, was achieved within 2-3 h in Phase I. During Phase II, the corresponding figures were 4.54-5.13% after 1.5-3 h. The difference was mainly due to an increase of freely-extractable steroids during Phase II. The difference can at least partly be explained by assuming a change in the kinetics of the metabolism of Org 2969 by pre-treatment with Org 2969 and ethinyloestradiol. The mean recovery of radio activity in urine and faeces was 83.0%/48.1%/34.9% (total/urine/faeces) of the total dose in Phase I and 76.1%/45.2%/30.9% during Phase II. The differences in the total excretion and in the radioactivity excreted in the faeces were significant.

PIP: Org 2969, a newly synthesized progestin from the laboratory of Organon Int B.V., Oss, the Netherlands, was ingested by women volunteers in an oral, radioactive dose to learn more about the drug's metabolism in humans. 4 female volunteeers were studied. The study was conducted in 2 phases, the first had volunteers ingesting about .1 mCi (50 mcg) of tritiated Org 2969 along with 50 mg of ethinylestradiol (as a single dose), and the second phase was a 10-day treatment with the same (50 mcg) dose of Org 2969 without radiolabel followed by administration of tritiated Org 2969. In Phase 1, peak level of total radioactivity occurred within 2-3 hours; this peak represented 3.16-5.02% of the dose administered per liter of serum. The corresponding figures for Phase 2 were 1.5-3 hours and 4.54-5.13%. Phase 2 samples had increased levels of freely-extractable steroids compared with Phase 1, which explains the difference in measurements. Another aspect of the difference in metabolism of the 2 doses must result from a change in kinetics of the metabolism of Org 2969 by pretreatment with Org 2969 (Phase 2) or simultaneous administration with ethinylestradiol (Phase 1). 1 level was significantly different between Phase 1 and 2 and that was amount of drug excreted in feces. In Phase 1, mean recoveries of radioactivity in urine and feces were 83%/48.1%/34.9% (total/urine/feces) and for Phase 2 the same recoveries were 76.1%/45.2%/30.9%.

The persistence and effects of rimexolone in arthritic and normal rabbit knee joints.

The persistence and effects of 3H-labelled and intra-articularly administered 11 beta-hydroxy-16 alpha,17 alpha,21-trimethylpregna-1,4-diene-3,20-dione (rimexolone, [3H]-Org 6216 have been investigated in a model of fibrin-induced mono-articular arthritis in the rabbit. It appears that joint swelling is suppressed in a dose-dependent way when the drug is administered into the arthritic joint. With a dose of 15 mg the joint circumference was restored to the initial value recorded prior to antigen challenge within 14 days. Administration of rimexolone into the non-arthritic joint also suppressed contralateral arthritic joint swelling, but this effect was less pronounced and shorter lasting. Radioactivity from [3H]-rimexolone at doses of 5 or 15 mg disappears slowly from both non-arthritic and arthritic knee joints.