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Biomedical subjects

T von Holst

Publications and source records attributed to T von Holst.

At least 19 recordsLinked to original sources
PubMed2002

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.

Administration, Cutaneous↗
PubMed2000

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.

Administration, Cutaneous↗
PubMed2000

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.

Adult↗
PubMed2000

[Alternatives to hormone replacement therapy: raloxifene and tibolone].

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.

Antihypertensive Agents↗
PubMed1999

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.

Adult↗
PubMed1995

[Serum lipids in treatment with transdermal estradiol and oral norethisterone acetate].

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.

Administration, Cutaneous↗
PubMed1994

[Oral or transdermal estrogen substitution therapy in climacteric?].

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.

Administration, Cutaneous↗
PubMed1994

[Endocrinological changes in pre- and 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)

Adult↗
PubMed1989

[Endocrinology of the climacteric].

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.

Climacteric↗
PubMed1988

[Significance of Chlamydia trachomatis for female fertility with special reference to prevalence in the 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.

Adult↗
PubMed1988

[Gonadotropin-releasing hormone receptors in human breast cancer tissue].

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.

Binding, Competitive↗
PubMed1983

Influence of severe obesity on peripheral hormone concentrations in pre- and postmenopausal women.

To investigate the influence of obesity on hormonal parameters in 186 apparently healthy women and in 176 women suffering from severe obesity the serum concentrations of FSH, LH, estrone (E1), estradiol (E2), androstenedione (A) and testosterone (T) were determined radioimmunologically. The climacteric onset of increased FSH production is 4 yr earlier (P less than 0.001) in obese than in normal women. Parallel to the rise of FSH there is a significantly premature decrease of the E1 and E2 concentrations in obese women. The typical elevation of the LH was found similar and not significantly different in the two collectives. The mean A levels are significantly lower (P less than 0.01) in obese than in normal women in all age groups. The T concentrations do not depend on the age of the women during the investigated period (41 to 60 yr) and are significantly higher (P less than 0.001) in the obese than in the normal women. There is a significant (P less than 0.001) correlation between the concentrations of A and E1 both in the obese and the normal women. An increased conversion of androgens to estrogens by adipose tissue is not revealed by the peripheral serum concentrations. Our data clearly demonstrate that in obese women the onset of ovarian insufficiency is significantly earlier than in normal women.

Adult↗
PubMed1982

Serum concentrations of FSH, oestradiol, oestrone and androstenedione in normal and obese women.

The normal ranges of the concentrations of follicle stimulating hormone (FSH), oestradiol (E2), oestrone (E1), and androstenedione (A) were established in 257 healthy women. The hormone levels of 84 normal post-menopausal women were compared with those from a group of 46 post-menopausal women with severe obesity (36.3 +/- 15.2 kg over the ideal weight). The increase of the FSH concentrations during the peri- and post-menopause occurs about 4 yr earlier in the obese than in the normal women. There is no significant difference, however, between the E2 levels of the normal and obese women. In the obese women, A (P less than 0.001) and E1 (P less than 0.05) levels are significantly lower than in the normal women. A weight reduction in the obese women had no influence on the concentrations of A and E2, whereas E1 levels tended to increase. FSH levels also increased significantly during weight reduction.

Adult↗
PubMed1981

[Progress in sterility therapy. Gonadotropin treatment, monitoring follicle maturation using real-time ultrasonics].

Results of prospective examination of follicle development under HMG-HCG-therapy by real time scanning are discussed. 1979-1980 37 patients were treated with HMG-HCG, 82 cycles of treatment were evaluated. In 93% of these cycles ovulation occurred, 17 patients became pregnant. Slight overstimulation was seen in 5% (4 of 82 cycles of treatment). Real time scan monitoring of follicular development allows a more efficient treatment with HMG-HCG, also multiple gravidity might theoretically be reduced.

Adult↗
PubMed1981

[Habitual abortion: diagnostics and therapy in gynaecological practice (author's transl)].

According to several literature surveys women with three consecutive and clinically ascertained spontaneous abortions appear to have without treatment an abortion risk of 50 to 60 per cent in the course of any further pregnancy. For improving prognostication various conditions leading to habitual abortions have to be clarified before the onset of a new pregnancy. Among our patients corpus luteum dysfunctions (35 per cent) and anomalies of the uterus (17 per cent) showed the highest frequency. Our patients also had an increased frequency of pathological spermiograms. Their influence on the incidence of habitual abortions remains, however, unclear. Infectious diseases and metabolic disorders (5 per cent) as well as chromosomal aberrations (6 per cent) appeared to be less frequent. Controversial views on the consequences of blood group incompatibilities of the spouses continue to exist. Conflict-oriented personalities of patients seem to play a major role. After evaluating the findings in literature pertaining to habitual abortions and on the basis of our own results (110 patients) diagnostic and therapeutic guidelines have been worked out. By employment of the individually required therapy 90 per cent of the patients with habitual abortions were able to successfully complete a further pregnancy.

Abortion, Habitual↗