Biomedical subjects
Publications and source records attributed to R Rolland.
In a series of 42 patients, the findings during fertility microsurgery were compared to the findings at both laparoscopy performed by referring gynaecologists and re-laparoscopy performed in our regimen. Since significantly fewer discrepancies were found in the latter group, this re-laparoscopy may be considered useful and justified. The importance of meticulous laparoscopy is emphasized.
Luteinising hormone-releasing hormone agonist (Buserelin) therapy administered for a period of 6 months in 4 patients with longstanding, severe, danazol-resistant endometriosis, was found to be effective in reducing all complaints related to endometriosis. From 2 weeks on, nearly half of the E2 determinations were below the sensitivity level of the assay, while the other values were predominantly in the range of the early follicular phase. Side effects associated with the induced hypoestrogenemia were mild and well tolerated. After six months of follow-up without treatment, one patient who desired pregnancy conceived shortly after cessation of therapy and one patient showed lasting amelioration of her complaints. The symptoms relapsed in the other two, possibly due to inadequate dose and/or duration of treatment.
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During laparoscopy peritoneal fluid samples were collected for FSH, LH, PRL, 17 beta-estradiol, progesterone, and total protein determinations in 100 women with a normal menstrual cycle. The samples were collected between cycle day -6 and cycle day +9, with the serum LH peak as a point of reference (day 0). The period investigated was divided into seven phases. FSH and LH concentrations in the peritoneal fluid varied in a cycle-dependent pattern that reflected the pattern in serum. In every phase of the cycle, however, peritoneal fluid FSH and LH concentrations were higher than or equal to the serum levels. This finding contrasts with the physiological behavior of other proteins in the peritoneal fluid. Peritoneal fluid 17 beta-estradiol and progesterone levels also varied in a cyclic pattern, with an increase in concentration immediately after ovulation and a decrease after the midluteal phase. With the exception of 17 beta-estradiol levels during the preovulatory phase of the cycle, peritoneal fluid levels of 17 beta-estradiol and progesterone were always equal to or higher than serum levels. The increase in 17 beta-estradiol concentration in the postovulatory phase was more gradual than that in the progesterone concentration. The elevated peritoneal fluid levels of gonadotropins in the preovulatory phase of the menstrual cycle were the most striking finding of the present study. This together with the finding of high peritoneal fluid to serum ratios of steroid hormones after ovulation shed new light upon the surroundings in which follicular development, ovulation, and fertilization take place.
Adult male Wistar rats were treated with Danazol (4 mg/day s.c.) for 52 days. The drug produced a marked, rapid drop in serum testosterone concentrations to very low levels and caused a slower decrease in serum FSH, LH and testis weight. Flow cytometric analysis of testicular cell suspensions showed a decline in the absolute numbers of haploid cells (spermatids), tetraploid cells (mainly pachytene spermatocytes) and of cells in the S-phase of the division cycle, suggesting that Danazol inhibited proliferation of spermatogonia and/or primary spermatocytes. Histological counting of the different types of spermatogonia, however, revealed no significant change in their numbers during Danazol treatment. It is concluded that Danazol inhibited spermatogenesis primarily after the preleptotene stage of primary spermatocytes.
During a laparoscopy that was performed between Day -6 and Day +9 of the cycle as related to the day of the LH peak (Day 0), the peritoneal fluid of 100 healthy female volunteers of proven fertility was collected and analysed. Peritoneal fluid volume and concentrations of total protein, albumin, alpha 1-, alpha 2-, beta- and gamma-globulins, IgA, IgG, IgM, haptoglobulin, acid-alpha 1-glycoprotein, alpha 1-antitrypsin, alpha 2-macroglobulin, C3-, C4- and C-reactive protein were determined. The peritoneal fluid volume and the concentrations of most proteins analysed showed an increase during the post-ovulatory phase of the period investigated. The peritoneal fluid:serum ratio of each individual protein showed a significant inverse correlation with its molecular weight. This confirms the assumption that peritoneal fluid is mainly an exudation product, most probably of ovarian origin.
Adult male Wistar rats were treated with a single injection (500 micrograms s.c.) of a new biodegradable depot formulation of the LH-releasing hormone (LHRH) analogue [D-Ser(But)6]AzGly10-LH-RH (Zoladex; ICI 118,630) to evaluate its potential for inhibiting spermatogenesis. The drug produced a marked (P less than or equal to 0.05) decrease in serum concentrations of FSH, LH and testosterone with a maximum effect 14 days after treatment. Since striking focal histological changes were seen in the testis after only 1 week, at a time when changes in serum gonadotrophins were minimal, there may be a direct effect of the LHRH analogue on spermatogenesis. Degenerative changes in germ cells as well as Sertoli cells could be observed. Flow-cytometric analysis of testicular cell suspensions showed a significant decline in the absolute numbers of haploid cells (spermatids), tetraploid cells (mainly pachytene spermatocytes) and of the numbers of cells in the S-phase of the cell cycle. This suggests that the drug also inhibits proliferation of spermatogonia and/or primary spermatocytes. Testis weight, serum hormone concentrations, and histological and cytological parameters returned to essentially normal values 52 days after the injection. It is concluded that this new method of administration may have practical and pharmacokinetic advantages for the purpose of reversible inhibition of spermatogenesis.
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Estrogen absorption from the neovagina was studied by administering 2.0 mg of micronized 17 beta-estradiol (E2) neovaginally to 6 patients. The neovagina in each patient was constructed by using the peritoneum from the pouch of Douglas. A mean peak of circulating E2 concentrations more than 15-times the basal level was achieved 90 min after the application. Until 12.5 h after the application, the E2 levels were significantly (P less than 10(-6)) elevated. FSH levels were significantly (P = 0.003) changed in comparison to the basal serum concentration. There was no significant (P = 0.08) change in LH levels. The resorption of estradiol from the neovagina is similar to that seen in women with normal vaginas.
Aromatase inhibition by delta 1-testolactone (TL), 500 mg twice daily for 4 weeks, in nine patients with idiopathic oligospermia lowered circulating estradiol (E2) levels by about 30%, enhanced the secretion of follicle-stimulating hormone (+ 30%), 17-hydroxyprogesterone (17-OHP) (+ 40%), and testosterone (T) (+ 30%), but did not affect serum luteinizing hormone levels. Despite E2 lowering, there was an accumulation of 17-OHP over T, suggesting 17, 20-lyase inhibition. Unexpectedly, administration of TL almost completely deleted the T response to continuous luteinizing hormone-releasing hormone infusion present before TL therapy, despite similar gonadotropin release. Because the 17-OHP response to the luteinizing hormone-releasing hormone infusion was even higher during therapy, the 17,20-lyase lesion seemed aggravated despite substantial reduction of E2 levels. Although the present data suggest that estrogens play a less dominant role in the origin of the late steroidogenetic lesion than previously assumed, the suggestion also arises that TL per se, in addition to its antiestrogenic action, exerts an inhibiting effect on the 17,20-lyase locus, which may obscure the beneficial effect of reducing E2.
In 77 of 115 cultures from uterine/tubal flushes performed in women undergoing diagnostic laparoscopy for reasons of infertility, epithelioid colonies of "tadpole-like" cells appeared. In cultured jet washings from the uterine cavities in women with ligated tubes, the same tadpole-like cells are present. These cells are also observed in vitro in laparoscopic biopsy specimens of active endometriosis nodules. Judged by the presence of cytokeratin in these cells, demonstrated by polyvalent or monoclonal antikeratin antibodies (the latter as a marker for glandular epithelia), there can be no doubt about their origin from the lining and glandular epithelium of part of the genital tract. Peritoneal washings not preceded by uterine/tubal flushing never contained the tadpole-like cells in culture. True epithelial cells were observed in the peritoneal cavity after flushing, and the proliferative capacity of these cells in vitro during the preovulatory phase was proven.
Serum levels of luteinizing hormone-releasing hormone (LH-RH), LH, and follicle-stimulating hormone (FSH) were measured for 60 minutes after 5- and 20-micrograms bolus doses of LH-RH given either intravenously or subcutaneously to 20 healthy men, for the study of LH-RH pharmacokinetics and the corresponding pituitary gonadotropin release. Intravenous (5- and 20-micrograms) LH-RH administration revealed much sharper LH-RH pulses, with significantly higher levels between 1 and 5 minutes (P less than 0.001) but lower levels between 30 and 60 minutes (P less than 0.05), compared with the subcutaneous route. No statistically significant differences were observed in the magnitude and time occurrence of maximum LH release or in the area under the LH response curves between intravenous and subcutaneous LH-RH administration, either in the 5-micrograms or in the 20-micrograms group. FSH responses were small and insignificant in all the performed tests. The intravenous route of administration seems preferential in therapeutic regimens that use pulsatile exogenous LH-RH, because the conditions of intermittent pituitary stimulation are more adequately fulfilled and the risk of dose accumulation is reduced. Furthermore, LH-RH doses of 5 micrograms are capable of producing adequate pituitary LH release, whereas increases in the pulse dose up to 20 micrograms seem to have no additional effects.
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