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Introduction: Postmenopausal hormone replacement therapy (HRT) has been described to reduce the risk of developing cardiovascular disease (CVD), which can be attributed at least in part to beneficial effects of oestrogens on serum lipoproteins. Little is known about a possible counteracting effect by the progestogen integrated in modern HRT regimens., Objective: To study the possible changes in serum lipids, lipoproteins and apolipoproteins during HRT with special emphasis on the possible progestational effect., Study Design: In an open-label longitudinal non-comparative study 23 healthy non-hysterectomized postmenopausal women were treated with continuous micronized 17 beta-oestradiol, 2 mg daily, in combination with cyclic dydrogesterone, 10 mg daily, the first 14 days of each 28-day treatment cycle. The women were followed for up to 2 years., Results: After 2 years serum total cholesterol and low-density lipoprotein cholesterol had decreased by 9.0% and 18%, respectively (P < 0.01), while high-density lipoprotein cholesterol had increased by 13% (P < 0.01). The latter change was accompanied with similar increases in apolipoprotein A-I (+16%; P < 0.01) and A-II (+13%; P < 0.01), while apolipoprotein B remained unchanged. Serum very low-density lipoprotein (VLDL) cholesterol and VLDL-triglycerides increased by 28% and 21%, respectively, the latter reflecting the slight increase in serum triglycerides by 21%. These values, however, remained within the normal range. Serum lipoprotein(a) decreased by 16% (P < 0.01). All calculated atherogenic indices decreased (P < 0.01) during the study period. Serum lipids and (apo)lipoproteins did not change after withdrawal of dydrogesterone for 14 days during the combination therapy in the last cycle studied. Serum fibrinogen decreased by 8.4% (P < 0.01) in the first 12 cycles, after which it increased to 13% above baseline value (P < 0.01 vs. baseline). Antithrombin III did not change and serum glucose decreased by 5.7%., Conclusions: This HRT regimen induces (and also when given for a longer period) beneficial changes in the lipid profile, without affecting important indicators of thrombosis. Also, the glucose metabolism does not seem to be interfered with. Cyclic administration of dydrogesterone does not unfavourably affect serum lipids and (apo)lipoproteins when combined with 17 beta-oestradiol supplementation. Therefore, this combination hormone regimen can be recommended for use in HRT.

Study Objective: To study the possible changes of reproductive hormones, sex hormone binding globulin, serum lipids and lipoproteins, lipoprotein (a) included, coagulation and glucose in postmenopausal women treated with 17 beta-oestradiol and cyclic dydrogesterone for 14 days per 28 days treatment cycle., Design: Open longitudinal prospective study., Duration: Twelve 28 days treatment cycles., Setting: Gynaecological department of university hospital., Subjects: 27 healthy postmenopausal women., Results: After treatment for six cycles serum concentrations of FSH and LH decreased significantly with 43.0% and 24.4%, respectively. Serum concentrations of 17 beta-oestradiol and oestrone increased significantly with 302% and 792%, respectively, and SHBG increased as well with 111% (P < 0.01). Serum total cholesterol decreased with 9.0% (P < 0.01). Serum VLDL-cholesterol did not change significantly. Serum LDL-cholesterol decreased with 16.3% (P < 0.01) and HDL-cholesterol increased with 8.0% (P < 0.01). This was accompanied with similar significant changes in the apolipoproteins: apolipoprotein A-I rose with 14.4% and apolipoprotein B decreased with 6.0%. Serum triglycerides and VLDL-triglycerides increased significantly with 14.4% and 17.9%, respectively. Lipoprotein (a) decreased with 17.5% (P < 0.01). These results more or less sustained at cycle 12 of treatment. Serum concentrations of antithrombin III and glucose did not change. Fibrinogen decreased slightly but significantly below the initial value., Conclusions: This combination replacement therapy gives beneficial changes in lipid-metabolism, indicating a reduced risk of developing coronary heart disease without unfavourably changing coagulation and glucose metabolism. The expected beneficial changes with oestradiol alone are not counteracted by the intermittent addition of dydrogesterone. Therefore this oestrogen/progestagen scheme can, indeed, be recommended for use in HRT.

A comparative immunocytochemical study was performed on endometriotic epithelial versus endometrial epithelial and normal mesothelial cells in order to obtain further evidence for either the endometrial implantation or mesothelial metaplasia theory. The three cell types could not be distinguished by keratin subtyping, using monoclonal antibodies (MAbs) to keratins 5, 7, 8, 14, 18, and 19. The epithelial markers HMFG-2 and BW 495/36, and a newly developed MAb NEND-3 (against endometrial cells) discriminated between generally negatively reacting mesothelial cells and positively reacting endometrial and endometriotic epithelial cells. The MAb NEND-3 appeared to be specific for endometrial (and endometriotic) epithelial cells since no reactivity with other epithelial cell types was found. Typing with MAbs against ovarian carcinoma related antigens (OV-TL 3, OV-TL 10 and OC 125) did not permit sufficient distinction. The marker profile of cultured endometrial, endometriotic and mesothelial cells confirmed the immunocytochemical findings on frozen sections. Although the data are consistent with the endometrial implantation theory, mesothelial metaplasia can not be excluded with regard to the histogenesis of endometriosis since metaplastic mesothelium may express different antigen markers.

Thirteen women with symptomatic enlarged leiomyomatous uteri completed 6 months treatment with the gonadotropin releasing-hormone agonist (GnRH-a) buserelin, 600 micrograms daily subcutaneously (s.c.). Seven patients received injections (200 micrograms thrice daily, I-group) and six infusion by pump (50 micrograms.min-(1).2 h-(1). P-group). Residual uterine volumes after 6 months therapy were comparable in both study groups (I-group median 37%, range 23 to 74%; P-group median 49%, range 30 to 69%), as were estradiol levels. Symptoms were well controlled within short time. Six months posttreatment follow-up revealed uterine regrowth to pretreatment dimensions in all but 1 patient with recurrence of symptoms in most women. During therapy, several biochemical indices of bone metabolism were significantly elevated, reflecting an increased bone resorption; they were restored within 3 months after cessation of therapy, except for alkaline phosphatase. Triglycerides and HDL-cholesterol did not change during study; cholesterol was slightly, but significantly elevated after 6 months therapy. GnRH-a buserelin, 600 micrograms daily by s.c. injection or infusion is equally effective in reducing enlarged leiomyomatous uteri. Discontinuation of therapy is followed by uterine regrowth with recurrence of symptoms in most women. The present mode of therapy seems to be beneficial as an adjunct before myomectomy, or in advancing menopause in symptomatic, climacteric women.

Forty-seven hyperprolactinaemic patients with serum prolactin (PRL) concentrations persistently above 1500 mU/l were treated with the new dopamine agonist CV 205-502 or bromocriptine in a prospective, randomized and double-blind fashion during a 24-week period. Two women had to be excluded because of poor compliance in the first month. Therefore 45 patients remained for evaluation. 81% of the patients in the CV 205-502 group and 70% of the patients in the bromocriptine group normalized their prolactin levels within the study period with a treatment dose as permitted in this protocol. In general serum prolactin normalized within 8 to 12 weeks of treatment. There were no differences between the two tested drugs regarding restoration of the menstrual cycle or disappearance of galactorrhoea. Both drugs gave rise to adverse reactions, especially during the initiation of therapy. However, the adverse reactions reported during CV 205-502 treatment were less severe and persistent than those attributed to bromocriptine. Patient acceptance of the new drug with regard to tolerability was judged by 90% of the women in that treatment group as very good or good, while 75% of those treated with bromocriptine evaluated its tolerability as very good or good. We conclude that CV 205-502 is highly effective in the treatment of hyperprolactinaemia with concomitant restoration of gonadal function and prevention of galactorrhoea. The tolerability of the drug seems better than of bromocriptine and therefore this drug is of value in the treatment of hyperprolactinaemic patients.

The fibrinolytic system of the peritoneum is important in the pathogenesis of adhesions. Plasminogen activator activity is depressed by serosal types of injury, which cause ischemia. Ischemic peritoneum induces fibrinous adhesions. When local fibrinolytic activity is impaired, persistence of fibrin and organisation of the fibrinous adhesions may occur. Peritoneal adhesion in rabbits were created by drying the serosa of the uterine horns and by introducing a small amount of blood intraperitoneally. In one group of rabbits tissue-type plasminogen activator (t-PA) was given intraperitoneally at the end of the operation: another group served as controls. 48 rabbits were operated on. The animals were killed 3 h, 1, 3 and 7 days postoperatively for evaluation of adhesions. All animals of the control group had adhesions. The animals of the t-PA group had less adhesions than the animals of the control group.

Thirty women who did not want to breast-feed postpartum were treated with Parlodel LA. Immediately after birth 50 mg Parlodel LA were injected i.m. by means of a double-chamber syringe. The aim was to investigate in an open study the clinical efficacy and tolerability of Parlodel LA in the prevention of postpartum lactation. The overall efficacy was very good in 29 women (96.6%) and good in 1 woman (3.4%). In 27 women no symptoms of tenderness, engorgement or milk secretion were found (90%). In two cases slight and moderate mammary pain were reported during a few days, engorgement in only one case during one day and in three cases a slight milk let-down was seen for 1-2 days. In all cases the breast symptoms ceased spontaneously and no rebound lactation occurred in any of the women treated with Parlodel LA. The general tolerability was very good in 29 cases (96.6%) and good in one case (3.4%). No adverse effects were reported in any case. No obvious changes in blood pressure were noticed after the injection. In general a slight decrease occurred in systolic and/or diastolic blood pressure post-partum well within the range of non-treated healthy postpartum women. There were also no signs of orthostatic hypotension or changes in pulse rate accompanying the slight decrease in blood pressure. The local tolerability at the injection site was very good in 23 women (76.6%). Seven had short-lasting pain, slight in 6 cases and moderate in 1. Slight redness was reported in one case.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

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.

A rat model has been created in which a single injection of an LH-RH analogue depot preparation (Zoladex, ICI 118630) produced a temporary interruption of the pituitary-gonadal axis. This effect applied during irradiation was investigated as a possible mechanism to protect the testis from radiation damage. A local testicular irradiation dose of 6.0 Gy was given either as a single dose or as a fractionated (2 X 3.0 Gy) dose at different time intervals ranging from 8 to 72 h. Stem cell survival was measured 11 weeks after irradiation by means of the repopulation index and the number of haploid cells (spermatids) measured by flow cytometry. Serum gonadotrophins and testosterone concentrations were measured to evaluate hormonal recovery. No significant differences were observed between serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone and the duration of the fractionation interval. Stem cell survival was higher following fractionated irradiation in comparison with the single dose. For the 8 h interval an increase in recovery ratio was found, amounting to a factor of 5 of the single dose value. The fluctuating pattern of the recovery curves indicated changes in radiosensitivity of stem cells. The combination of hormonal inhibition of spermatogenesis and fractionated irradiation led to a decrease in the absolute numbers of stem cells. However, the stem cell recovery curves were identical to those seen without hormonal inhibition. It was concluded that hormonal pretreatment with Zoladex during split dose irradiation had no protective effect on stem cell survival.

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.

The gonadotrophin release and the changes in ovarian and adrenal steroid levels following the administration of a low dose of LHRH were assessed in a group of women with clinical features of the polycystic ovary syndrome (PCO syndrome). The results were compared with those obtained in a group of normal ovulatory women. A significant increase in LH and FSH levels and a decrease in cortisol concentrations were demonstrated in both study groups following the administration of LHRH. The LH response was significantly exaggerated in the PCO group when compared with the control women. The estrone and estradiol levels did not change in either group. The androstenedione and testosterone concentrations did not change or decreased in the control group, whereas an increase of these hormones was seen in the PCO group. In the PCO group a positive correlation between the LH response and the androstenedione response was noticed. These findings indicate that the hyperandrogenic state encountered in PCO patients is at least in part of ovarian origin.

Prolactin is a mammotropic hormone essential for the initiation of lactation. It also influences ovarian function; during hyperprolactinemia hypogonadism occurs. This is true for pathological forms of hyperprolactinemia but also for the early puerperium when there is physiological hyperprolactinemia. Amenorrhea is a better parameter of hyperprolactinemia than galactorrhea. The mechanisms by which prolactin disrupts ovarian function are not as yet fully understood; it probably alters hypothalamic neurotransmitter content through a direct feedback mechanism resulting in a decrease of Gn-RH. However, the direct effect of prolactin-producing pituitary tumors on the capacity of the gonadotrophs or a direct interference of prolactin at the gonadal level are also possibilities. Hyperprolactinemia can be treated very effectively with bromocriptine and this drug appears to have become the favorite form of treatment. In the case of obvious tumors hypophysectomy is indicated. When there are smaller tumors irradiation of the pituitary gland previous to bromocriptine treatment may prevent expansion of the gland during subsequent pregnancy.

The aim of the present study was to determine whether a group of patients selected on the basis of clinical features only is characterized by the typical hormonal findings as discussed in the literature concerning the PCO-syndrome. PCO patients had oligomenorrhea, secondary amenorrhea or otherwise evidence of chronic anovulation, as well as hirsutism and/or obesity. Control women had regular menstrual cycles and a normal body weight. Since androgen and estrogen production in women depends on the stage of follicular development, an effort was made to obtain endocrinological data under standardized conditions. Under well-defined circumstances the PCO group (n = 20) had higher LH levels and lower FSH levels as compared with the control group (n = 10). Consequently the LH/FSH ratio was significantly elevated in the PCO group. Serum estrone and estradiol levels were significantly elevated in the PCO group, as were the serum levels of androstenedione and testosterone. Despite these differences a marked degree of overlap existed in the PCO patients and the control women for gonadotropin, estrogen and androgen levels. It was concluded that although the presence of polycystic ovaries in the investigated PCO group of women was not confirmed by laparoscopy, laparotomy or histological examination of the ovaries, these women had basal endocrinological characteristics similar to those found in well-proven PCO patients reported in the literature.

The time of ovulation in various hamster colonies and its relationship with the period of light as reported in the literature was compared with the observations made in this study. Ovulation and transport of ova to the oviduct was studied during days 4 and 1 of the estrous cycle. Microscopical examination of the various oviducal segments for the presence of ova resulted in a detailed description of physiological ovum transport for the adult golden hamster. Simultaneously the developmental stages of ova were checked together with the occurrence of unfertilized ova and the percentage of ova implanted in the uterus. Finally, the contractility of the oviduct in vitro was observed for groups of animals at different times in the pre- and postovulatory period. The presented data indicate that the golden hamster is useful for the study of ovum transport processes. This is due to the regularity of its estrous cycle including multiple ovulations, and because ovum transport can easily be monitored microscopically with a high degree of reliability.

The prolactin-lowering and lactation-inhibiting effects of lisuride and bromocriptine, two dopaminergic drugs, were compared in a double-blind study. Twenty-six women took lisuride, 0.2 mg b.i.d., and 24 women took bromocriptine, 2.5 mg b.i.d., during 14 days postpartum. Though both drugs gave satisfactory inhibition of puerperal milk production, in these dosages bromocriptine was a more effective lactation inhibitor and prolactin suppressor. After discontinuation of treatment rebound symptoms were more pronounced in the bromocriptine group than in the lisuride group.

Recently, several reports have suggested that salicylazosulfapyridine causes a reduction in semen quality in patients with ulcerative colitis. After withdrawal of the drug pregnancies have been reported. The aim of this report is to offer additional data to the discussion on the deleterious effect of salicylazosulfapyridine on semen quality. Two case reports are presented with a review of the literature.