[Amenorrhea rate after switch from sequential hormone replacement therapy to continuous combined administration of low dose estradiol and norethisterone acetate]. / Blutungsfreiheit nach der Umstellung von einer sequenziellen Hormonersatztherapie auf die kontinuierlich kombinierte Gabe von niedrig dosiertem Estradiol und Norethisteronacetat.

OBJECTIVE: Patient's wishes for a hormone replacement therapy (HRT) without withdrawal bleedings are decisive for a good compliance. Systematic experience concerning the bleeding profile when switching from a sequential hormone replacement therapy (s.c.HRT) to a continuous combined hormone replacement therapy (c.c.HRT) is sparse. This non-interfering study is designed to investigate the bleeding profile after such a switch. MATERIAL AND METHODS: 1 018 gynaecological centres recruited 3 917 patients pretreated with a s.c.HRT for this study. The switch from the s.c.HRT to the c.c.HRT was performed with a low-dose combination of 1 mg estradiol plus 0.5 mg norethisterone acetate (NETA). The bleeding profile was evaluated after 6 to 9 months of treatment according to the patient's diaries. RESULTS: Amenorrhoea was reached in 74.4 % of the enrolled patients after 3 months, in 90.6 % after 6 months, and in 92.1 % after 9 months of treatment. At the time of the switch to the c.c.HRT, already 32.4 % of the women were free of withdrawal bleedings. Parameters like age of the patients, body mass index (BMI), dosage of the estrogen during pretreatment did not influence the results considerably. 92.7 % of the physicians and 92.5 % of the women rated the combined treatment of 1 mg estradiol and 0.5 mg NETA (Activelle) as satisfactory. CONCLUSION: The switch from a s.c.HRT to a continuous combined treatment with 1 mg estradiol plus 0.5 mg NETA can be performed without problems, resulting in a high rate of amenorrhoea and a high acceptance of physicians as well as patients.

Estradiol and levonorgestrel: effects on bleeding pattern when administered in a sequential combined regimen with a new transdermal patch.

OBJECTIVE: A 1-year, randomized, multicenter study was carried out to assess the effects of estradiol/levonorgestrel, delivered transdermally by 7-day patches in a sequential combined regimen, on bleeding pattern and acceptability in postmenopausal women. METHODS: A total of 468 postmenopausal women were randomized to 15-cm2, 22.5-cm2 or 30-cm2 patches containing 17 beta-estradiol alone (50, 75 or 100 micrograms/24 h, respectively) for 2 weeks followed by 17 beta-estradiol/levonorgestrel (50/10, 75/15 or 100/20 micrograms/24 h) for 2 weeks. RESULTS: The occurrence of cyclic bleeds was dose-dependent, with an increase at higher dosages; the frequency of a cyclic bleed per treatment cycle was 40% in the 50/10 micrograms/24 h patch, 62% in the 75/15 micrograms/24 h patch and 76% in the 100/20 micrograms/24 h patch. The incidence of intermittent bleeding also increased with higher doses, from 22% in the 50/10 group to 35% in the 100/20 group; 20% of women in the 50/10 group did not bleed at all; the corresponding figures for the 75/15 and 100/20 groups were 7% and 0%, respectively. Time of onset of cyclic bleeding was constant in all groups. The mean duration of cyclic bleeding was constant within each group, but increased from 4.4 days in the 50/10 to 6.3 days in the 100/20 group. The regularity and predictability of cyclic bleeding were high in all groups. Recurrence of cyclic bleeds was acceptable for most women (90%). CONCLUSIONS: Sequential combined transdermal 17 beta-estradiol/levonorgestrel shows very good cycle control that is well accepted by postmenopausal women.

Endometrial safety and tolerability of AERODIOL(R) (intranasal estradiol) for 1 year.

OBJECTIVE: the purpose of this study was to assess the endometrial safety and patient acceptability of a pulsed estrogen therapy provided by S21400 (intranasal 17 beta-estradiol) in the treatment of postmenopausal symptoms. DESIGN: postmenopausal women (n=408) entered an open-label, community based, multicentre trial. Patients received S21400 plus sequential (>90% of patients) or continuous progestogen. Treatment was initiated with a standard daily dose of 300 microg but dose adaptation was possible every 3 months from 150 to 600 microg daily. Endometrial biopsies were performed at entry and at 12 months, and bleeding patterns were recorded at 3-monthly intervals throughout the trial. RESULTS: 71% of patients received 300 microg per day S21400 throughout the study, 3% had their dose decreased, 19% had their dose increased and 7% had their dose both decreased and increased. Three hundred and eleven biopsies were obtained after 12 months of treatment, there were no cases of endometrial hyperplasia. The 95% confidence interval [CI] for the rate of incidence was 0-1.2%. Cyclical bleeding occurred in 82% of sequential treatment cycles. Unexpected bleeding occurred in 5% of the treatment cycles. Presence of unexpected bleeding varied according to the treatment regimen, 15 and 4% of the cycles with combined continuous and sequential regimen, respectively. Unexpected bleeding was mostly spotting. Nasal treatment was well accepted. Nasal symptoms (itching sensation, rhinorrhea and sneezing) were mostly mild in intensity and they led to treatment withdrawal in approximately 3% of patients. The rate of treatment continuation was 85% at 1 year. CONCLUSIONS: S21400, in combination with continuous or sequential progestogen, exhibits good endometrial safety and patient acceptability in postmenopausal women.

[Alternatives to hormone replacement therapy: raloxifene and tibolone]. / Alternativen zur Hormonersatztherapie: Raloxifen und Tibolon.

The bone is an active metabolic organ influenced by many substances like calcium, vitamin D, bisphosphonates etc. The postmenopausal osteoporosis is mainly caused by estrogen deficiency and hormone replacement therapy (HRT) has been shown to prevent the progress of osteoporosis. The following paper describes two alternatives to the classical HRT: raloxifen and tibolon. Raloxifen belongs to the selective estrogen receptor modulators (SERM) showing an estrogen-agonistic effect on bone. There is evidence that bone mineral density (BMD) is growing with treatment. In a three year study (MORE), a statistically significant decrease of lumbar spine fractures was demonstrated (RR 0.5-0.7). Furthermore there was a statistically significant reduction of receptor positive breast cancer (RR 0.10). Raloxifen shows beneficial effects on the lipids and does not induce endometrial proliferation. In the field of climacteric complaints, it is an estrogen-antagonist and therefore inappropriate for this indication. Tibolon--a steroid hormone--and their three metabolites have estrogenic, gestagenic and weak androgenic effects on the different target organs. As expected, there is an increase of bone mineral density comparable to that of HRT or raloxifen; data of fracture rates with long-term therapy are missing. The substance and their metabolites are equivalent to HRT in the treatment of climacteric complaints. Tibolon shows some beneficial effects on the lipids and a lower bleeding rate compared to HRT. Raloxifen and tibolon are interesting alternatives to HRT which allow a more individual treatment of patients in the postmenopause.

Clinical equivalence of intranasal and oral 17beta-estradiol for postmenopausal symptoms.

OBJECTIVE: The aim of this study was to demonstrate clinical equivalence between a novel intranasal estradiol formulation and a reference oral drug. STUDY DESIGN: In this multinational, double-blind, parallel-group study 659 postmenopausal women with moderate to severe postmenopausal symptoms were randomly assigned to receive either 300 microg/d intranasal 17beta-estradiol (S21400) or 2 mg/d oral micronized estradiol, plus the appropriate placebo, for 24 weeks. All patients also received 10 mg/d dydrogesterone for 14 days per 28-day cycle. Adjustment of intranasal dosage was permitted from week 14 on. The primary efficacy criterion was the Kupperman index at week 14, with a predefined limit of equivalence of 4. RESULTS: Kupperman index scores improved similarly in the 2 groups, from 28.4 +/- 6.2 to 10.0 +/- 8.6 (mean +/- SD) for S21400 and from 28.1 +/- 6.0 to 8.9 +/- 8.0 for oral therapy, with a difference between groups at week 14 of 1.1 +/- 0.6 (90% confidence interval, 0. 0 to 2.2). This was below the predefined equivalence limit of +4 for statistical noninferiority (P <.001). The daily number and intensity of hot flushes decreased similarly in the two treatment groups. Withdrawal bleeding was 20% less frequent with intranasal therapy (90% confidence interval, 12.5 to 27.6). Severe mastalgia was less frequent in the S21400 group (1.0%) than in the group with oral therapy (5.2%; P <.01). Triglyceride and angiotensinogen levels increased significantly with oral therapy but not with S21400. The same number of patients required dose adaptation in the 2 groups (approximately 20%). CONCLUSION: Intranasal administration of 300 microg/d estradiol was at least as effective as oral administration of 2 mg/d estradiol in alleviating postmenopausal symptoms, with less frequent mastalgia and uterine bleeding and without the metabolic consequences of the first-pass effect.

Efficacy and tolerability of a new 7-day transdermal estradiol patch versus placebo in hysterectomized women with postmenopausal complaints.

OBJECTIVES: To investigate the efficacy and tolerability of a continuously applied 7-day-Estradiol patch (Fem7, Merck KGaA, Germany) delivering 50 microg estradiol per day in the treatment of hysterectomized women with postmenopausal complaints compared with placebo. DESIGN: A multicentre, randomized, double-blind study with an initial screening phase (phase I), a 3-month double-blind placebo-controlled phase (phase II) and a 3-month open follow-up phase (phase III). METHODS: 186 patients were randomized for a 3-cycle placebo-controlled study followed by a 3-cycle open follow-up (total duration; 6 months). The changes in Kupperman Index (primary efficacy variable), hot flushes and urogenital symptom score were studied from baseline to the end of the study. In addition, skin tolerability was assessed and patients were also asked to grade the subjective acceptance of therapy. RESULTS: A reduction in Kupperman Index was observed in both groups, and at each cycle of the placebo-controlled treatment phase the 7-day-Estradiol patch was superior compared with placebo (last value vs. baseline P = 0.0006). From the second treatment week onwards a distinct difference was noted in the reduction of hot flushes from baseline between the 7-day-Estradiol patch group and the placebo group. The difference between the groups was statistically significant for each cycle and at the end of the controlled treatment phase (mean weekly hot flush reduction at the end of the placebo-controlled treatment phase: -32.5 for the 7-day-Estradiol patch vs. -22.0 for placebo, P = 0.0025). The efficacy of the 7-day-Estradiol patch within the application period did not show any difference between days 1-3 and 4-7. Subjective acceptance of the 7-day-Estradiol patch was good and 72.4% of patients who took active medication throughout the study were willing to consider continuing its use. CONCLUSIONS: The 7-day-Estradiol patch is well tolerated and provides effective relief of moderate to severe vasomotor symptoms in hysterectomized women, with a rapid onset of action and 7-day duration of therapeutic effect. Although a placebo effect was observed, the 7-day-Estradiol patch significantly reduced hot flushes and other menopausal symptoms throughout the application period.

Serum leptin levels and body weight in postmenopausal women under transdermal hormone replacement therapy.

Leptin, the adipocyte-specific product of the ob gene, is implicated in body weight regulation and energy balance. We investigated the influence of hormone replacement therapy (HRT) on the body mass index (BMI) and serum leptin levels in 20 postmenopausal, nonobese women treated with transdermal HRT (delivery rate 50 microg 17beta-estradiol/24 h, 1 patch per week) for 6 months. Serum leptin levels were measured by ELISA and results were compared by means of the Student's paired t-test or Pearson's correlation. The mean patient age was 55+/-6.04 years. The mean body weight prior to the start of the study was 69.39+/-9.37 kg, and the BMI before HRT was 26.92+/-4.47 kg/m2. Both parameters remained unchanged under therapy. No significant change in absolute serum leptin values (18.8+/-8.4 ng/ml; 20.47+/-9.7 ng/ml; 17.92+/-8.7 ng/ml at 0, 4 and 6 months respectively) or in adiposity-corrected values (serum leptin/BMI) (0.68+/-0.24; 0.75+/-0.29; 0.67+/-0.26 at 0, 4 and 6 months respectively) were found. Serum leptin levels correlated well with BMI (r = 0.7193, p<0.0001). There was no significant correlation of estradiol with serum leptin levels before or during therapy. In summary, low dose, transdermal HRT exhibited no influence on serum leptin levels or BMI in postmenopausal women. These data suggest that low dose HRT does not influence body weight regulation in postmenopausal women.

Postmenopausal hormone replacement therapy and the vascular wall: epidemiology and clinical studies.

The clinical relevance of estrogen's multiple acute and more delayed effects on vascular wall structure and function is incompletely understood. This review attempts to reevaluate epidemiological findings and clinical studies concerning the vascular actions of estrogens and gives implications for strategies in postmenopausal hormone replacement therapy (HRT). There is large evidence from observational studies that HRT reduces the risk of cardiovascular mortality and morbidity in postmenopausal women. However, according to the only large randomized, placebo-controlled, secondary prevention Heart and Estrogen/progestin Replacement Study (HERS), women with prevalent cardiovascular disease (CVD) have increased CVD events within the first year after onset of HRT. The net effects of HRT on atherosclerosis, coagulation, fibrinolysis or the inflammatory response are unproven. Randomized trials of intermediate outcomes reveal that HRT has favorable effects on isolated cardiovascular risk factors, e.g. lipoproteins, carbohydrate metabolism and vasodilatation, but the impact of this effects on clinical endpoints is still not clear. The basis of "evidenced based medicine" is currently not sufficient to provide exact recommendation who will benefit from HRT and who might not. Therefore, the decision about hormone use should consider individual benefit-risk profiles.

Add-back medrogestone does not prevent bone loss in premenopausal women treated with goserelin.

To investigate the effect of medrogestone on bone mineral density (BMD) and bone turnover under conditions of estrogen withdrawal, premenopausal women with endometriosis were treated with goserelin (Zoladex), combined with either placebo (group A, n = 12) or 10 mg medrogestone (Prothil, group B, n = 11) for six months, and followed for an additional six months. Lumbar spine BMD was measured at 0 and 6 month. Markers of bone turnover were serum bone alkaline phosphatase (sBAP) and osteocalcin (sOC) by ELISA, and urinary total pyridinoline (uPYD) and deoxypyridinoline crosslinks (uDPD) by HPLC. Patients in both groups had a similar and significant decrease in BMD after 6 months (4%, p < 0.01). The time course of changes in bone turnover, in contrast, was different in both groups. In group A, crosslink excretion increased from one month onwards, while no changes were seen in group B. In group A, sBAP levels rose during treatment, while in group B, this rise was delayed until treatment was terminated. Additionally, group B showed an initial suppression of sBAP and sOC. In both groups, sOC increased after treatment was discontinued. Medrogestone at 10 mg/d does not prevent lumbar bone loss in premenopausal women under estrogen deprivation. In the medrogestone add back group, the changes in bone turnover are compatible with low turnover bone loss,as ooposed to a state of high turnover seen in the unopposed goserelin group. This effect may be due to glucocorticoid receptor mediated actions of medrogestone on bone.

[Serum lipids in treatment with transdermal estradiol and oral norethisterone acetate]. / Serumlipide unter Behandlung mit transdermalem Ostradiol und oralem Norethisteronacetat.

With transdermal estradiol substitution the so called "primary liver passage" is avoided. Taking into account also the low dose of estradiol the risk of hepatic side effects can be reduced. On the other hand, it was assumed that for the same reason desirable lipid effects regarding cardiovascular protection may also not be possible, in contrast to oral estrogen treatment. Treating 26 postmenopausal women with the estradiol patch releasing 0.05 mg daily and with 1 mg oral norethisterone acetate, added at least during 10 days in each cycle, a significant reduction was observed in total cholesterol as well as in LDL- and VLDL-cholesterol of about 15-20%. HDL-cholesterol first showed a decrease and thereafter it increased again to basic level. It is supposed that the reason for this may be different effects on subfractions of HDL-cholesterol. The triglycerides were lowered to about 20%. This result is thought to be important because oral estrogens have been associated with increases in triglycerides. By lowering LDL-cholesterol as well as triglycerides, both serum lipids, most important with respect to cardiovascular protection, are shown to be influenced positively.

[Endocrinological changes in pre- and postmenopause]. / Endokrinologische Veränderungen in der Prä- und der Postmenopause.

The endocrinology of the perimenopause--the time between pre- and postmenopause--is characterized by changes in the metabolism of the steroid hormones caused by increasing insufficiency of the ovaries. Until the age of 48 the concentrations of the estrogens are relatively constant with a median level of 120 pg/ml serum for estradiol and of 75 pg/ml for estrone. Between the age of 49 and 54 the levels decrease to concentrations of 35 pg/ml for estrone and 10 pg/ml for estradiol. In the corresponding time, there is a tenfold rise of the level of FSH. The level remains constant until high age. The decrease of the estrogens causes the menopause in an age of 51 to 52. In the postmenopause the ovaries don't play a role for the concentrations of the estrogens. The concentrations are determined by the conversion of the androgens secreted by the adrenal cortex. The serum concentrations of androstenedione are five times higher than those of testosterone. The function of the adrenal cortex remains until high age; there is no 'adrenopause' comparable to the 'menopause'. The suppression of the adrenal cortex by treatment with corticoids (e.g. for asthma) causes a dramatic decrease of the androgens and consecutively for the estrogens. The lack of estrogens play an important role in the induction of osteoporosis and other disturbances of the late postmenopause, e.g. coronary heart disease. Obese women show in the pre- and the perimenopause more often dysfunctional bleedings caused by anovulation or corpus luteum insufficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

[Oral or transdermal estrogen substitution therapy in climacteric?]. / Orale oder transdermale Ostrogensubstitutionstherapie im Klimakterium?

There are several preparations available for hormone substitution in the postmenopause. The aim of this paper is to give a short review on oral and transdermal hormone substitution therapy. Are there different effects, side effects or metabolic interactions? Both the oral and the transdermal application are similar in reduction of menopausal symptoms. Neither vaginal cytologic differences, nor different bleeding patterns and no increase in weight or blood pressure changes can be observed with either application form. Despite a local irritation of the skin (3-7%) with transdermal oestradiol, only 4% of the patients show systemic side effects either with oral or transdermal hormone substitution. The oral administration results in higher 17 beta-oestradiol levels, higher oestrone levels and an increase in some liver proteins, possibly as a result of the first pass effect of the liver. The cardioprotective effects of oral hormone substitution are well known. Furthermore transdermal oestradiol therapy results, also in a decrease of cholesterol and atherogenic LDL-C levels. In contrast to oral oestrogens, no effect on triglycerides or its decrease can be observed; in view of conflicting results regarding HDL-C, further studies are necessary. With both applications, there are no clinically relevant alterations in thyroid, carbohydrate- or blood coagulation metabolism: Even the prevention of osteoporosis in postmenopausal women, which is establish with oral hormone therapy, can also be observed with transdermal hormone substitution.

[Control of uterine contractions with fenoterol. II. Significance of the beginning, duration and manner of therapy for the status of the newborn infant and early childhood development up to 4 years of age]. / Wehenhemmung mit Fenoterol. II. Bedeutung von Beginn, Dauer und Art der Therapie für den Zustand des Neugeborenen und die frühkindliche Entwicklung bis zu vier Jahren.

From 1976 to 1979, 404 pregnant women were treated with the tocolytic agent Fenoterol. The data of pregnancy, delivery and the children's development up to four years of age were computerized and correlated to the duration, beginning date and type of treatment. Compared to long lasting tocolytic treatment, delivery was significantly earlier after short term treatment, resulting in acompromined development of the infants. Early start of treatment and long lasting application, mainly the case in high risk pregnancies, postponed the delivery and induced normal development of the children. When the intravenous route was necessary the state of the newborn and the post partum development were less satisfactory than after oral medication, the latter developing without complications. Based on our results, late damages of Fenoterol on developmental parameters up to four years of children's age appear to be non existent.

[Treatment of endometriosis]. / Therapie der Endometriose.

In a randomized study, the effect of gestrinone (2 x 2.5 mg/week) was compared with the effect of danazol (3 x 200 mg/day) in treating 30 patients with laparoscopically proven endometriotic implants for 6 months. Therapy was effective in 80%-90% of cases and pregnancy rates were similar, but the incidence of side effects was different in the groups. In addition, buserelin (900 micrograms/day intranasally) was investigated in a multinational, multicenter trial in 275 patients. In 80%, GnRH agonist treatment induced the disappearance or reduction of endometriotic implants. The main side effects were due to estrogenic suppression. Presently, various methods of hormonal treatment are under investigation, especially to determine recurrency rates of endometriosis and long-term side effects.

[Endocrinology of the climacteric]. / Endokrinologie des Klimakteriums.

The endocrinology of the menopause is determined by the decrease of estrogens. In 250 healthy patients there was an observed decrease of estrone to 35 pg/ml and of estradiol to 10 pg/ml serum between the 49th and 54th year of age. Thereafter no further decline occurred, because the androgen precursors of the estrogens were secreted by the adrenal cortex until advanced age. In a period of 30 years there was a decrease of the androgen levels of only 25%. In 200 patients with severe obesity we found no differences in peripheral steroid concentrations, but the SHBC concentrations were significantly lowered; therefore, the amount of free active estradiol and the effect on the target organ is higher in these patients.

[Tocolytic treatment with fenoterol. I. Prospective study of the effect of tocolysis on the condition of the newborn infant and early childhood development up to 4 years of age]. / Wehenhemmung mit Fenoterol. I. Prospektive Untersuchung zum Einfluss der Tokolyse auf den Zustand des Neugeborenen und die frühkindliche Entwicklung bis zu vier Jahren.

From 1976 to 1979 a prospective study was run at the Women's Hospital of Heidelberg in which every women was registered who attended the hospital before the 20th week of pregnancy. After delivery the infants' development was followed up to four years. During this time 404 women received fenoterol and 74 of them had premature deliveries. While 20% of the women were primarily treated with fenoterol before the 20th week of pregnancy (threatened abortion, cerclage), 80% received the drug in the 2nd and 3rd trimester (premature contractions, abnormal fetal heart rate pattern, premature opening of the external os etc.). Risk factors and early childhood development were compared with 465 women seen in the same time who had never needed fenoterol. The data of the patients' history, the course of pregnancy, and the state of the newborn, revealed that the risk of premature delivery in spite of tocolytic treatment was highest in young women, women with low bodyweight, women with a history of miscarriages, women with threatened abortion and women with anaemia during pregnancy. In correspondence with prematurity, the development of these children was delayed. The same factors of risk were demonstrated in women with successful tocolytic treatment and delivery after the 37th week of pregnancy, although their neonates were in a markedly better state. Early childhood development in this group did not differ from that in the group of women with deliveries after the 37th week and without tocolytic treatment.

[Significance of Chlamydia trachomatis for female fertility with special reference to prevalence in the endometrium]. / Bedeutung von Chlamydia trachomatis für die weibliche Fertilität under besonderer Berücksichtigung der Prävalenz im Endometrium.

144 patients with longstanding infertility (mean duration of infertility 4.9 years) were screened for endometrial infection with Chlamydia trachomatis by means of endometrial biopsy and McCoy cell-culture. The same day blood was taken for detection of Chlamydia IgG antibodies in serum samples. During a 1 year's period, all new patients of a large infertility clinic without complaints or clinical symptoms of infection of the lower genital tract were consecutively submitted to the study. Elevated titers of IgG antibodies in serum samples (Chlam. AB greater than or equal to 1/256) revealed previous chlamydial infection of 26% of patients, but Chlamydia trachomatis was detected in endometrial biopsies in only 5/144 (3.5%). There was a strong correlation of previous chlamydial infection and reduced tubal patency (p 0.001) and a lower pregnancy rate after 6 months. The results suggested that infections with Chlamydia trachomatis, influenced by demographic and socio-economic aspects, are of minor importance as an actual infection in asymptomatic patients with longstanding infertility. Previous chlamydial infections, however, are of great importance because of their negative influence on tubal function.

[Gonadotropin-releasing hormone receptors in human breast cancer tissue]. / GnRH-Rezeptoren im menschlichen Mamma-karzinomgewebe.

Analogues of gonadotropin-releasing hormone (GnRH) are presently being investigated for the treatment of metastatic breast cancer. Although their effects are thought to be mediated via the suppression of gonadotropins and gonadal steroids, they could possibly also act directly on the tumour. The binding of a GnRH-agonist to membrane fractions of 97 primary human breast carcinomas was investigated. In 43 cases (44%) the presence of specific GnRH receptor binding sites (above 3 fmol/mg membrane protein) was shown. GnRH receptor content was 6.2 fmol/mg membrane protein in estradiol receptor (ER) positive tissues and in ER negative tissues 2.0 fmol/mg membrane protein (p less than 0.05). Progesterone receptor (PR) positive contained 5.2 fmol/mg protein and PR negative carcinoma contained 2.0 fmol/mg membrane protein. In postmenopausal women GnRH receptor concentration was 5.4 and 2.9 fmol/mg membrane protein, respectively, in ER positive and negative tissues (p less than 0.05) whereas 4.4 and 5.2 fmol/mg membrane protein, respectively, in PR positive and negative samples. Binding of GnRH was positive (above 3 fmol/mg protein) in 33% premenopausal and in 54% of postmenopausal cases. Further clinical studies with GnRH analogues will clarify the therapeutic value of GnRH receptor determination in breast cancer.