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Biomedical subjects

J Hammerstein

Publications and source records attributed to J Hammerstein.

At least 55 records · Page 3Linked to original sources
PubMed1983

A Sertoli-Leydig cell tumor and pregnancy. Clinical, endocrine, radiologic, and electron microscopic findings.

An extremely rare case of a conception occurring in a 26-year-old patient with a small virilizing Sertoli-Leydig cell tumor (diameter: 0.6 cm), bilateral polycystic ovaries and non-tumorous adrenal hyperandrogenism is presented. Prepregnancy findings included hirsutism, clitoromegaly, secondary amenorrhea, and elevated peripheral plasma testosterone (T; 5.7 ng/ml). Extensive basal steroid screening, dynamic function tests, conventional radiologic procedures, selective glandular vein catheterization, and laparoscopy failed to localize unequivocally the source of androgen excess, but suggested bilateral adrenal involvement. The patient conceived during the diagnostic work-up; peripheral T levels increased to 12.1 ng/ml within the first trimester. An exploratory laparotomy with left adrenalectomy, right adrenal biopsy and left ovarian wedge resection revealed an incompletely removed Sertoli-Leydig cell tumor, but normal adrenal histology. The pregnancy was terminated, a left oophorectomy and right ovarian wedge resection were performed at 14 weeks' gestation. Subsequently, peripheral androgens returned to normal, regular menses resumed, and hirsutism disappeared. Three years later the patient delivered a healthy female infant.

Abortion, Therapeutic↗
PubMed1983

Antiandrogens in the treatment of acne and hirsutism.

The review discusses (1) the relationship between the endocrine actions of antiandrogens and their therapeutic efficacy and (2) recent chemical and pharmacokinetic data on cyproterone acetate (CPA). It also provides (3) a comparison of CPA and spironolactone regarding the tentative benefits and risks and offers (4) general rules for the drug treatment of androgenized women. Clinical results indicate that those agents are most effective which not only competitively inhibit androgen binding at the receptor level but also suppress androgen secretion and/or production. The combined mode of action is observed with CPA as well as spironolactone. Pharmacokinetic studies underline the necessity to restrict CPA administration in huge doses to the first half of a treatment cycle in order to avoid bleeding disturbances. Also it appears that individual differences in CPA bioavailability do not satisfactorily explain the lack of therapeutic response in about 30% of the cases. Data are presented hinting that the 15 beta-hydroxy-, metabolite of CPA may actually be the biologically active agent. In addition preliminary results are given indicating that intramuscular CPA is therapeutically more effective than oral CPA.

Acne Vulgaris↗
PubMed1983

The diagnostic value of plasma free testosterone in non-tumorous and tumorous hyperandrogenism.

The clinical significance of total and free testosterone (T) estimates for the diagnostic approach to hirsute patients was assessed. Plasma T was measured by radioimmunoassay and its non-protein-bound fraction was determined by equilibrium dialysis, thus facilitating the calculation of apparent free T (AFT). The cases of 162 subjects were investigated; the subjects included 75 women in whom glandular androgen release had been defined by selective catheterization. A positive linear correlation was observed between both parameters over a wide range of concentrations (T, 153 to 10,700 pg/ml; AFT, 0.8 to 342 pg/ml; P less than 0.001). Significant differences of mean T and AFT levels were found between healthy control subjects (n = 8) and subjects with non-tumorous hyperandrogenism (n = 60; P less than 0.005). Individual values overlapped considerably; elevated T (greater than 640 pg/ml; 48%) or AFT (greater than 7.2 pg/ml; 52%) were present in only half the hirsute women. However, the upper 95% confidence limits of normal for both indices were exceeded in all patients with androgen-secreting ovarian tumors (n = 7). It is concluded that the indirect estimation of AFT in addition to T is time-consuming, costly, without practical value in selecting the proper treatment, and therefore not mandatory in the routine evaluation of androgenized women.

Adolescent↗
PubMed1983

[Treatment of virilized women with intramuscular administration of cyproterone acetate].

Management of hirsutism with high-dose oral cyproterone acetate (CPA) is associated with a failure rate of about 30%. The present investigation analyses the efficacy of parenteral CPA administration in non-tumorous hyperandrogenism. Medium-dose CPA (300 mg) was injected intramuscularly once per month, followed by oral ethinylestradiol (40 micrograms daily) for 21 days in 42 patients (total of 293 treatment cycles). The onset of withdrawal bleeding was 3 to 8 days later. This regimen was used as primary therapy (group A; n = 18) as well as follow-up therapy in low-dose (group B; n = 10) and high-dose oral standard CPA failures (group C; n = 14). The following satisfactory or good response rates were observed in regard to hirsutism: group A 83,5%, group B 100%, group C 57%; seborrhea A and B 100%, C 89%; acne and androgenetic alopecia A and B and C 100%. Clinical side effects occurred in 20 patients; they corresponded in type and frequency to those elicited by the high-dose oral standard medication and resulted in termination of treatment in only 3 patients. Pilot studies regarding the pharmacokinetics of CPA as well as the effects on plasma total and free testosterone and prolactin failed to explain the therapeutic superiority of parenteral CPA (n = 7 women). Still, it may be concluded that intramuscular CPA administration represents a new and highly effective means of managing hirsute females.

Acne Vulgaris↗
PubMed1983

Effects of various replacement oestrogens on hepatic transcortin synthesis in climacteric women.

The influence of peri-menopausal oestrogen replacement therapy upon protein synthesis in the liver was investigated. Changes in the cortisol-binding capacity of transcortin (TC-BC) were utilized as an indicator of hepatic oestrogen sensitivity. Forty-two climacteric women were studied before and after treatment with various drugs at different doses (patients receiving identical compounds served as their own controls for the evaluation of dosage effects; duration of medication: 14 days at each dose). Oral administration of oestriol (1 and 2 mg daily; n = 6), oestriol (1 and 2 mg daily) + oestradiol-17 beta (2 and 4 mg daily; n = 8), oestradiol valerate (1, 2, 4 and 6 mg daily; n = 6), conjugated equine oestrogens (0.3 and 0.6 mg daily; n = 6), sodium oestrone sulphate (0.8 and 1.6 mg daily) + sodium equilin sulphate (0.2 and 0.4 mg daily; n = 6) and quinoestrol (25 micrograms daily; n = 6) failed to alter TC-BC. However, ingestion of higher doses of conjugated equine oestrogens (0.9 and 1.25 mg daily; n = 5) and quinoestrol (50 micrograms daily; n = 6) caused a significant rise (P less than 0.01). Ethinyloestradiol was given orally as a reference substance and elicited an elevation of expected magnitude. Vaginal administration of dienoestrol cream (1 mg daily; n = 4) did not change TC-BC. These data indicate that the hepatotrophic effects of replacement oestrogens vary depending on the preparation and dosage selected for treatment.

Climacteric↗
PubMed1982

Vaginal administration of ethinylestradiol: effects on ovulation and hepatic transcortin synthesis.

Ethinylestradiol (EE) was given vaginally to circumvent the intestinal metabolism and initial liver passage which follow oral intake. This route of administration was chosen in an effort to enhance the antiovulatory potency of EE, while decreasing adverse hepatic reactions. Vaginal tablets containing 20-30 micrograms of EE were taken daily by 7 ovulating volunteers from day 5 to day 25 of the menstrual cycle. The regimen resulted in serum EE levels of 62 +/- 27 pg/ml (mean +/- S.D.) 8-10 hours after insertion. Ovulation was inhibited in 5 women (monophasic basal body temperature curves, serum progesterone levels of 0.9 +/- 1.1 ng/ml during the second half of the treatment cycle). The cortisol-binding capacity of transcortin was significantly elevated in all subjects (52.3 +/- 6.4 micrograms/100 ml; controls 25.7 +/- 2.2 micrograms/100 ml). These findings indicate that intravaginal EE is twice as potent as oral EE in regard to inhibition of ovulation as well as stimulation of the hepatic transcortin synthesis. Vaginal administration apparently increases the bioavailability of EE; it does not facilitate a selective reduction of estrogenic effects upon the liver.

Adult↗
PubMed1982

Anti-estrogenic effects of contraceptive progestins on the dynamics of gonadotropin release.

The hypophysiotropic effects of ethinylestradiol (EE) alone and in combination with three different progestins at various doses were assessed in 39 normal women. The compounds were given orally for 7 to 21 days. Serum LH and FSH were measured before and after GnRH double stimulation (2 x 25 micrograms i.v. at a two-hour interval); the ratio between second and first response served as an index of gonadotropin-synthesis capacity. Compared to pretreatment early follicular phase controls (LH and FSH ratios of 1.3 and 1.4), administration of 40 and 50 micrograms of EE daily elicited a significant amplification of LH and FSH synthesis (LH ratios of 2.2 and 3.3; FSH ratios of 2.8 and 3.3). By contrast, 80 micrograms of EE daily caused little change. The EE-induced rise of pituitary responsiveness to GnRH could be counteracted by the addition of progestins. The degree of inhibition as dependent on the type and dose of the progestational compound. It is concluded that the standardization GnRH double stimulation technique may serve as a pharmacodynamic model to quantitate the estrogenic and anti-estrogenic effects of contraceptive steroids at the pituitary level.

Adult↗
PubMed1982

Estradiol and progesterone receptor concentrations and 17 beta-hydroxysteroid-dehydrogenase activity in estrogen-progestin stimulated endometrium of women with gonadal dysgenesis.

Four hypergonadotrophic women between 25 and 37 years of age with gonadal dysgenesis were treated sequentially with estrogens and a progestin. The hormonal environment induced by this therapy was similar to that of ovulating women, as demonstrated by serum levels of estradiol, endometrial histology and pituitary gonadotropin secretion before and after LH-RH double stimulation. The concentrations of estradiol and progesterone receptors (ER and PR) and the activity of the 17 beta-hydroxysteroid-dehydrogenase (17 beta-HSD) were determined in endometrial curettings obtained from the above patients at 5 different days of their 28-day artificial cycles. The results were correlated to the histology of the endometrium and the serum concentrations of estradiol at the corresponding days of the cycle. The cytoplasmic ER and PR concentrations in the endometrium were 3-6 times higher during the estrogen than progestin phase of the induced endometrial cycle. For the activity of the 17 beta-HSD, the contrary was the case, being 6-10 fold higher during the progestin phase. A 22-day administration of estrogens only did not lead to a rise in enzyme activity or decrease in receptor content as observed under progestin influence after day 14. Since ER and PR concentrations and 17 beta-HSD activities were similar to those in the endometrium of normally ovulating women, these results confirm experimentally the present concept concerning the dependence of the cytoplasmic ER and PR content and 17 beta-HSD activity on female sex hormone action.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1981

Inhibitors of acrosomal proteinase as antifertility agents. A problem of acrosomal membrane permeability.

In vitro studies were performed to investigate the accessibility of acrosin to various proteinase inhibitors inside the intact acrosome of testicular, ejaculated, and uterine human spermatozoa. As test system the gelatin plate assay was used. For this assay it was shown formerly that a correlation exists between the size of the digested lysis areas (halo formation) and acrosin activity estimated with synthetic substrates. In addition, saturation of the gelatin substrate membranes with acrosin inhibitors including highly specific ones before application of spermatozoa completely prevented halo formation indicating that the gelatinolytic activity of human spermatozoa is caused exclusively by acrosin. When human spermatozoa were incubated with various acrosin inhibitors (concentration: 1 mmol/l) prior to application to the gelatin membrane, reduction of halo formation could not be observed, however. This result indicates that most of the tested acrosin inhibitors (9 naturally occurring protein inhibitors, 2 microbial peptide inhibitors, 19 synthetic inhibitors) were unable to penetrate the acrosomal membranes of testicular, ejaculated, and uterine human spermatozoa. Only 2 inhibitors caused moderate up to complete inhibition of the gelatinolytic activity of the spermatozoa if applied in concentrations between 1 and 10 mmol/l: the proteinase inhibitor aprotinin and the synthetic inhibitor NPGB (4-nitrophenyl 4-guanidinobenzoate). Obviously, human acrosomal membranes seem to be especially impenetrable to proteins, polypeptides, and synthetic agents. Those acrosin inhibitors penetrating the human sperm head membranes are either too toxic or the local concentration necessary for effective acrosin inhibition in vivo cannot be achieved within the male or female genital tract secretions. Therefore, acrosin inhibitors cannot be used for human contraception at present. Thus it is mandatory to continue the search for suitable acrosin inhibitors with low toxicity easily penetrating into the intact sperm acrosome.

Acrosome↗
PubMed1981

XY gonadal dysgenesis: aberrant testicular differentiation in the presence of H-Y antigen.

Six patients with pure nonmosaic 46,XY gonadal dysgenesis (XY GD) and histocompatibility H-Y antigen titers in the normal male range (H-Y+) are presented. Clinical characteristics included a female phenotype, masculine skeletal characteristics, signs of virilization, and primary amenorrhea. All individuals had unambiguous female external genitalia, a hypoplastic uterus, bilateral tubes, and streak gonads. Histomorphologic evaluation of the gonads revealed various abortive testicular and ovarian elements capable of steroid production. Gonadal tumors were found in 4 patients (gonadoblastoma, dysgerminoma, granulosa cell tumor, myxofibroma). Plasma and urinary androgens and basal and stimulated gonadotropin levels were elevated prior to gonadectomy. Data show that the presence of the H-Y antigen per se does not guarantee normal testicular organogenesis. It is hypothesized that defective H-Y antigen binding to its gonadal receptors triggers aberrant testicular differentiation in 46,XY H-Y+ GD.

Adult↗
PubMed1980

Medium dose cyproterone acetate (CPA): effects on hormone secretion and on spermatogenesis in men.

Medium dose cyproterone acetate (CPA; 10 mg daily p.o.) was administered to 10 fertile men for 12 weeks. Hormonal measurements and semen analyses were performed before, during (4th and 12th week) and after CPA treatment. At the hypothalamo-pituitary level CPA significantly reduced the hypophyseal storage and synthesis capacity for gonadotropins. Basal LH and FSH concentrations were suppressed by 30% and 40%, respectively; while basal prolactin was elevated by 75%. The episodic fluctuations of peripheral gonadotropins remained unaffected. At the testicular level CPA significantly decreased basal testosterone and dihydrotestosterone concentrations by 70% and 50%, respectively. The pulsatile pattern of androgen secretion was abolished. CPA also inhibited spermatogenesis and motility. No serious clinical side effects were observed. All changes appeared to be completely reversible. It is concluded that medium dose CPA induces progestational/anti-gonadotropic effects at the hypothalamo-pituitary level in addition to its antiandrogenic action at the testicular level.

Adult↗
PubMed1979

[Contraception in androgenised women with a low-dose cyproterone-acetate containing one-phase preparation (author's transl)].

101 hirsute women received Diane, a combination of 2 mg cyproterone acetate and 50 micrograms ethinyl oestradiol per capsule, from the fifth to twenty-fifth day during a total of 1105 cycles. The treatment was satisfactory in 96% of women with acne, 84% with androgenic alopecia, 79% with seborrhoea, and 50% of those with mild or moderate hirsutism. The effectiveness of treating hirsutism or alopecia depended on its severity and duration. There was no correlation between various measures of androgen levels before and during treatment and the clinical results. Side effects were similar to those after contraceptive one-phase preparations, both in kind and incidence. None of the women became pregnant. Diane is thus the drug of choice in hormonal contraception of patients with acne, seborrhoea, androgenic alopecia or mild hirsutism. It is also suitable in the follow-up or interval management of high-dose cyproterone acetate treatment of severe hirsutism, in order to maintain the effect obtained with lower hormone doses.

Acne Vulgaris↗