摘要:

Abstract.Model systems were evaluated, which can be used to determine biological activities of progestogens at various cell levels of the anterior pituitary gland. in addition, various progestogens at different dose levels were tested in females to evaluate the ovulation inhibition dose. the association of progestogens with the cytosol receptor of the adenohypophysis of the rat was studied in vitro. Sucrose gradient centrifugation analysis revealed material sedimenting in the 4‐5 S and 6‐7 S region, resp., and both binding proteins were found to specifically bind progestogens. a small displacement by cortisol was observed in the 4‐5 S area. Relative affinity constants were estimated for various progestogens by incubation of cytosol samples with radioactive labeled progestins, and a close correlation between affinity and biological activity was recorded. Adult female rats seven days after castration were used to study the influence of various progestogens on LH‐RH stimulated gonadotropin release. Levonorgestrel was found to augment LH‐RH provoked LH release in vivo, whereas both basal as well as LH‐RH stimulated FSH serum levels were noted to be impaired at higher doses of the steroid. Similarly, δ15‐levonorgestrel was observed to increase the response of LH to LH‐RH. on the other hand, δ15‐levonorgestrel greatly augmented basal as well as LH‐RH induced FSH serum levels up to a dose of 10 μg. At 100 μg of δ15‐levonorgestrel FSH serum levels were suppressed again. But, only 1/3 of the levonorgestrel dose was necessary to produce these effects, i. e. δ15‐levonorgestrel was found ca. 3‐times more potent than the native progestogen. Experiments performed in a cell culture system of anterior pituitary cells revealed an impairment of LH‐RH stimulated gonadotropin release. LH and FSH release was suppressed to 40 and 50%, resp., at ED50of LH‐RH in the presence of 3×10−8M levonorgestrel. LH and FSH release was reduced to 50 and 70%, resp., when anterior pituitary cells were incubated with LH‐RH in the presence of 3×10−8M δ15‐levonorgestrel. Thus, cell culture experiments also suggested that the potency of the δ15‐derivative of levonorgestrel was ca. 3‐times more potent. Analysis of patterns of cervical scores and karyopyknotic index as well as of serum levels of 17β‐estradiol, progesterone, LH and FSH revealed a borderline ovulation inhibition dose of levonorgestrel and δ15‐levonorgestrel at 50 and 30 μg, respectively. Cyproterone acetate, which is used in an oral contraceptive to treat acne and hirsutism was found to inhibit ovulation at a borderline dose of 1 mg. the present data combine to suggest that all model system are efficient to evaluate new progestogens, and that δ15‐levonorgestrel exerts a some 3‐times greater biological activity than levonorgestrel itself. Thus, a dose reduction of the pr

ISSN:0001-6349    

DOI:10.3109/00016347909157223

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

摘要:

Abstract.In order to investigate the possible ovulation inhibitory effect of a new oral contraceptive containing a combination of 20 μg ethinyl estradiol and 250 μg levonorgestrel peripheral serum from five healthy women between 17 and 24 years were analysed for FSH, LH, estradiol 17‐β and progesterone. the measurements were carried out during a control cycle before the treatment, during two treatment cycles and during a subsequent control cycle. in addition, serum levels of ethinyl estradiol and norgestrel were determined during the treatment periods. Radioimmunological methods were utilized for all the measurements. in all five women studied there was a complete inhibition of ovulation during treatment as indicated by a lack of mid‐cycle LH peaks and by suppression of normal luteal phase levels of progesterone. Four out of the five women showed no biphasic estradiol pattern. During treatment the serum levels of levonorgestrel varied between 1 and 10 nmol/1 while the levels of ethinyl estradiol usually were below the limit of detection for the method used (below 85 pmol/1). Post‐treatment control cycles revealed a reestablishment of the ovulatory pattern in four of the five

ISSN:0001-6349    

DOI:10.3109/00016347909157224

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

摘要:

Abstract.It has previously been reported that subdermal implants containing d‐norgestrel inhibit ovulation through blockage of the positive feedback action of estrogen on luteinizing hormone (LH) release. in this study 100 μg of LH‐releasing hormone (LRH) were injected intravenously to test the pituitary reserve capacity for gonadotrophin secretion in three women with three 40 mg d‐norgestrel rods implanted subdermally for more than one year. the gonadotrophin release to LRH varied and seemed related to the ovarian steroid concentrations at the time of the LRH infusion in a manner similar to that seen during the normal menstrual cycle. It is concluded that low plasma levels of d‐norgestrel do not inhibit the pituitary responsiveness to LRH. the results indicate that the blocking action of the gestagen on the positive feedback of estradiol on LH release occurs at the hypothalamus or higher CNS

ISSN:0001-6349    

DOI:10.3109/00016347909157225

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

摘要:

Abstract.Peripheral plasma from five young women was analyzed for cyproterone acetate and ethinyl estradiol during a period of 96 hours duration after single oral intake of a coated tablet of DIANE® (2 mg of cyproterone acetate+50 μg of ethinyl estradiol), and during a treatment cycle of 21 days during which the formulation was given daily. Radioimmunoassays were utilized for quantifications. a maximum concentration of 11.0 ± 3.4 ng of cyproterone acetate/ml plasma was found 1.6 ± 0.6 hours after a single administration of DIANE®. Postmaximal disposition took place in two phases with half‐lives of 1.9 ± 0.6 hours and 2.2 ± 0.2 days. the maximum level of 0.08 ± 0.03 ng of ethinyl estradiol/ml plasma was found 1.6 ± 0.6 hours after such single administration. Following commencement of a daily oral intake of DIANE® a steady state was reached by the 5th to 8th days, during which 24 hours after each dose cyproterone acetate concentrations were found to be 2.4 ± 0.7 times higher than at the corresponding time after a single administration. Accordingly, after the first third of the 21 day treatment cycle an almost constant plasma level was reached indicating an equilibrium of intake and elimination. Except for a change in the mean terminal half life after multiple dosing, there was evidently no change in the kinetics of cyproterone acetate. No pointers to an accumulation of ethinyl estradiol upon daily administration of DIANE® c

ISSN:0001-6349    

DOI:10.3109/00016347909157226

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

摘要:

Abstract.The combination of 2 mg cyproterone acetate, a pronounced antiandrogenic substance, in combination with 0.05 mg ethinyl estradiol has undergone intensive multiphasic clinical evaluation. the preparation with the trade name Diane®has proven to be not only a reliable contraceptive, but also a very potent drug for the treatment of both acne and seborrhea, and of milder cases of hirsutism. the effect of Diane®on markedly increased hair growth was not so pronounced. in addition to the presentation of the most pertinent steps of the clinical investigation of Diane®, the possible mode of actions of antiandrogens alone and in combination with an estrogen is discuss

ISSN:0001-6349    

DOI:10.3109/00016347909157227

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

摘要:

Abstract.A new generation of combined oral contraceptive containing staggering amounts of ethinyl estradiol and levonorgestrel (SH B 264 AB) was compared in a randomized multicentre trial with a well established low dose combined pill composed of 30 μg ethinyl estradiol plus 150 μg levonorgestrel (Neovletta®) in a total of 489 women over 2,777 cycles. the trial was planned to run for six consecutive months at three clinics in Sweden (296 women) whereas the remaining 193 volunteers were enrolled from clinics in Great Britain and Germany. the case report forms were designed in a fashion to permit evaluation of the two formulations with regard to their overall reliability and acceptability in terms of cycle control. No pregnancy occurred during the observation period. Out of the total number of patients approximately 90% completed the six months treatment period on both combinations. Bleeding irregularities, such as spotting and/or breakthrough bleeding occurred more frequently on Neovletta® compared with SH B 264 AB (15.7% versus 10.1% of women) although the total hormone intake is considerably lower using the triphasic formulation. Missed withdrawal bleeding was reported in 2.3% of the total cycles on the fixed combination and in 0.9% of the total cycles on the triphasic regime. of the 72 (14.7%) women, 36 on each drug, who did not complete the six months of treatment, 44 discontinued for medical reasons. the discontinuation rate for medical reasons, the most common of which was spotting, was 8% for both formulations. From the present study it can be concluded that the new triphasic formulation is just as safe as Neovletta®, but it seems to be superior to the fixed 30 μg ethinyl estradiol plus 150 μg levonorgestrel‐pill in terms of a lower incidence of bleeding irregu

ISSN:0001-6349    

DOI:10.3109/00016347909157228

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

摘要:

Abstract.The orthostatic circulatory reaction, the physical working capacity on a bicycle ergometer, the blood pressure reactions at rest both during and after the ergometer test, the total hemoglobin content and the heart volume in the supine position were all determined on four separate occasions in 34 nulligravidae who were taking a low estrogen dose steroid oral contraceptive consisting of 30 μg of ethinyl estradiol and 150 μg of levonorgestrel (known as Neovletta®, Schering AG). These examinations were performed once prior to the commencement of this medication, and 6, 12 and 24 months thereafter. the orthostatic pulse and blood pressure reactions taken on these subjects standing upright for a period of eight minutes were pronounced up to and including the 12 month control, but decreased thereafter. Physical working capacity at a pulse rate of 170 beats per minute on the different test occasions decreased up to and including the 12 month control, but thereafter seemed to increase almost to their initial levels. Blood pressure, heart volume and total amount of hemoglobin increased up to and including the 12 month control but thereafter seemed to return to the pre‐treatment level. These circulatory changes during the first year of the application of this contraceptive may be as the result of a marked sympathicotonic reaction induced by the steroids. Possibly because of some form of adaptive mechanism, this reaction seems to decrease (and almost to “normalize”) during the second yea

ISSN:0001-6349    

DOI:10.3109/00016347909157229

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

摘要:

Abstract.Seventy‐five menstruating women seeking contraceptive advice were randomly allocated to treatment with combined oral contraceptives containing either ethinyl estradiol 30 μg+levonorgestrel 150 μg (30/150), ethinyl estradiol 50 μ+levonorgestrel 125 μg (50/125) or ethinyl estradiol 50 μg+levonorgestrel 250 μg (50/250). the concentrations of cholesterol, phospholipids, high density lipoprotein (HDL)‐cholesterol, HDL‐phospholipids and triglycerides were determined prior to treatment and after one, three and six months of medication. Triglycerides increased by 18‐42 per cent after one to six months of treatment with 50/125. the HDL‐cholesterol and HDL‐phospholipids were reduced by 10 per cent during 50/250 medication. No other parameters showed any consistent alteration in any of the treatment groups. Raised triglyceride concentration and/or decreased HDL concentration may increase the risk for cardiovascular disease. It is therefore suggested that in order not to alter the HDL concentration a combined oral contraceptive agent should probably not contain more 19‐nortestosterone type of progestogen than corresponding to 125‐150 μg of levonorgestrel. to avoid a rise of the triglyceride level the weight relation between levonorgestrel and ethinyl estradi

ISSN:0001-6349    

DOI:10.3109/00016347909157230

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

摘要:

Abstract.The authors suggest expressing the amount of use of contraceptives in a female population in the same terms as used to denote the occurrence of births, with one year of contraceptive use regarded as an event in the same sense as a birth. If the prevalence of contraceptives in a population can be expressed in the same terms as other events associated with reproduction, such as births and abortions, it may help to clarify the relationships between these events. Applying the method used to calculate the total fertility and abortion rates on the use of oral contraceptives and intrauterine devices in Sweden in 1975, they noted 1.8 deliveries, 0.6 legal abortions and seven years' use of oral contraceptives and six years' use of intrauterine device per women.

ISSN:0001-6349    

DOI:10.3109/00016347909157231

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

ISSN:0001-6349    

DOI:10.3109/00016347909157232

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY