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Biomedical subjects

M H Birkhäuser

Publications and source records attributed to M H Birkhäuser.

At least 19 recordsLinked to original sources

Differential impact of conventional oral or transdermal hormone replacement therapy or tibolone on body composition in postmenopausal women.

OBJECTIVE: To compare the effects on body composition and body weight of tibolone vs two different sequential oral or transdermal oestrogen-progestogen hormone replacement therapies versus no therapy. PATIENTS AND METHODS: One hundred postmenopausal women were assigned to a control group (n = 26), or randomized to 1) tibolone (TIB) 2.5 mg/day (n = 28), 2) oral oestradiol 2 mg/day (PO) plus sequential dydrogesterone 10 mg/day for 14 of 28 days per cycle (n = 26), or 3) transdermal oestradiol patch (TTS) releasing 50 micrograms/day plus oral sequential dydrogesterone 10 mg/day for 14 of 28 days per cycle (n = 20). Body composition was measured at the base-line and every 6 months for 2 years by DXA (Hologic QDR 1000 W). RESULTS: Total body fat mass increased (P < 0.05) in controls (+3.6 +/- 1.5%) and in TTS treated (+4.7 +/- 2.2%), but not in PO (-1.2 +/- 2.4%) and TIB (-1.6 +/- 2.2%) treated subjects. This increase in total fat mass in controls and TTS treated women was mostly due to an increase in fat mass of the trunk (P < 0.05), but not legs. As a result, a redistribution of body fat to the trunk occurred in controls, TTS and TIB, but not in PO treated women (P < 0.05). Total lean body mass decreased (P < 0.02) in controls (-1.7 +/- 0.7%) and PO (-1.4 +/- 0.6%) but not in TTS (+0.3 +/- 0.8%) and TIB (+0.4 +/- 0.5%) treated subjects. CONCLUSIONS: The menopause is associated with an increase in total body fat and a decline in lean body mass. Oral oestradiol/dydrogesterone and tibolone prevent total body fat changes, whereas transdermal oestradiol/oral dydrogesterone and tibolone prevent the lean mass changes. Furthermore, oral oestradiol/dydrogesterone prevents the shift to a central, android fat distribution.

Absorptiometry, Photon

Serum pregnancy-specific beta1-glycoprotein before embryo transfer is related to endometrial thickness and to outcome prognosis in women undergoing in-vitro fertilization treatment.

We have previously observed the repeated presence of low but detectable amounts of the trophoblast marker pregnancy-specific beta1-glycoprotein (SP1) in the serum of some women undergoing in-vitro fertilization (IVF) treatment around the time of oocyte retrieval. The occurrence of these signals seemed to be restricted to a defined group of patients which also showed a lower pregnancy success rate in a preliminary study. To test our hypothesis we have analysed 173 consecutive cycles leading to an embryo transfer. Fifty-four cycles (31%) had a serum SP1 level of at least 0.1 ng/ml between days embryo transfer -5 and embryo transfer (group A). Five pregnancies were obtained in this group (pregnancy rate = 9.3%), while in group B, defined by the absence of detectable SP1 before embryo transfer (119 cycles), 36 ongoing pregnancies were achieved (30.3%). Ten of the 41 pregnancies were achieved in 33 first-time non-pregnant patients undergoing further attempts during the study period. Again the pregnancy rate was higher in the first-time group B women (9/23 versus 1/10 for group A). Patients tended to remain in their groups A or B, the latter being associated with a better immediate as well as subsequent chance for pregnancy. Group A cycles had a significantly lower endometrial thickness two days before oocyte retrieval than group B (P = 0.0011). We postulate that the presence of an unknown, maternal and progesterone- or follicle stimulating hormone-independent factor in some patients could stimulate tonic ectopic SP1 synthesis and at the same time negatively influence endometrial development.

Adult

Placental protein 14 and pregnancy-specific beta 1-glycoprotein in women with suppressed, normal and stimulated follicular maturation.

Not only the ovarian steroids but a number of proteins have an effect on the endometrium and its capability to accept an implanting embryo and to establish a pregnancy. In this study we have selected the placental protein 14 (PP14) which is, in spite of its name, produced by the glandular epithelium of the endometrium. Pregnancy-specific beta 1-glycoprotein (SP1) was also investigated. This marker is trophoblast-specific but it has been chosen since some patients repeatedly exhibit weak but detectable serum SP1 when no embryo is present. There seems to be a negative correlation between the chance of obtaining a pregnancy and the occurrence of such abnormal serum SP1 signals; they could originate from the endometrium itself or from another maternal source influencing the endometrium indirectly. The full-cycle time course was determined for these two proteins as well as for estradiol and progesterone. A total of 66 cycles were analyzed, of which 16 were from ovulating volunteers without any hormonal treatment (controls) and 13 were from women taking oral contraceptives. The remaining 37 cycles were from 32 patients undergoing conventional in vitro fertilization (IVF) treatment. Eight pregnancies were achieved in this group during the study period. We found that abnormal positive SP1 signals occurred predominantly in the unsuccessful IVF subgroup, but also in the control groups (with or without contraceptive pills), and this in a cycle-independent manner. PP14, on the other hand, exhibited cyclic patterns in the IVF and ovulating control cycles as did progesterone. However, in seven out of 13 cycles under oral contraception (and suppressed progesterone), a midcycle rise in PP14 was observed. Moreover, midcycle PP14 levels were generally higher in this group when compared to the ovulating controls as well as to the cycles under controlled ovarian stimulation for IVF. This confirms that PP14 is influenced by progesterone but only in an indirect way or under the additional effect of other hormones. It is unlikely that SP1 plays this role since it was not correlated to any of the other proteins or steroids studied. Nevertheless, SP1 did not occur randomly over the different groups.

Adult

Comparison of transvaginal ultrasonography and endometrial biopsy in endometrial surveillance in postmenopausal HRT users.

OBJECTIVES: To compare transvaginal ultrasonography with histological findings in endometrial evaluation of postmenopausal women using hormone replacement therapy and to evaluate endometrial safety of three hormone replacement therapy regimens. METHODS: In a randomized, comparative study in postmenopausal women, endometrial safety was evaluated using (1) no hormone replacement therapy, (2) oral micronized 17 beta-estradiol/oral sequential dydrogesterone, (3) transdermal 17 beta-estradiol/oral sequential dydrogesterone, or (4) oral tibolone. 85 Non-hysterectomised subjects underwent transvaginal ultrasonography immediately before Pipelle biopsy at baseline and subsequently after 12 and 24 months. Endometrial thickness and uterine dimensions were determined by transvaginal ultrasonography, and endometrial thickness (double-layer) was compared with biopsy results. RESULTS: Endometrial evaluation was conveniently performed by transvaginal ultrasonography, and endometrial thickness correlated well with biopsy findings. If endometrial thickness was < 5 mm, the endometrial biopsy sample was either inactive/atrophic or insufficient for histopathological diagnosis. Hyperplastic or malignant changes were not reported. After 24 months, endometrial thickness was increased both in the oral (P < 0.001) and transdermal (P < 0.001) 17 beta-estradiol/dydrogesterone groups, whereas with tibolone the change in endometrial thickness was not different from controls. CONCLUSION: transvaginal ultrasonography of the endometrium reliably predicts the histological picture in hormone replacement therapy users. Using 5 mm endometrial thickness as cut-off point, more than 75% of biopsies could be avoided. All three hormone replacement therapies were safe with respect to the endometrium. With sequential 17 beta-estradiol/dydrogesterone the expected progestogen-induced secretory pattern was observed, whereas endometrial histology under tibolone closely mimicked the natural atrophic postmenopausal state.

Administration, Cutaneous

Long-term influence of different postmenopausal hormone replacement regimens on serum lipids and lipoprotein(a): a randomised study.

OBJECTIVE: To assess the influence of three different postmenopausal hormone replacement therapies on levels of serum lipids and lipoprotein(a) [Lp(a)]. DESIGN: Open, randomised, controlled study. PARTICIPANTS: One hundred and forty healthy, early postmenopausal women. INTERVENTIONS: The women were randomised to receive continuous 17 beta-oestradiol, either orally (2 mg daily; n = 35) or transdermally (50 micrograms daily; n = 35), plus 10 mg dydrogesterone daily for 14 days of each 28-day cycle; or 2.5 mg tibolone daily (n = 35). Thirty-five untreated women acted as controls. MAIN OUTCOME MEASURES: Fasting blood samples were analysed at baseline, 6, 12 and 24 months for low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol, very low density lipoprotein (VLDL), total cholesterol, triglycerides, lipoprotein(a)[Lp(a)], apolipoproteins A-1, A-2 and B, fibrinogen, and antithrombin factor III. RESULTS: At 24 months oral oestradiol increased mean HDL cholesterol (7%; 95% CI 1-14), compared with no change in the transdermal group and a decrease of 26.8% in the tibolone group (95% CI 22.9-30.5); oral oestradiol decreased mean LDL cholesterol (11.8%; 95% CI 6.3-19), compared with no change in the tibolone group. Changes in apolipoprotein A-1 and B showed a similar pattern to HDL and LDL cholesterol, respectively. Oral oestradiol increased serum triglycerides (30%; 95% CI 18-42) after 24 months, compared with no change in the tibolone and transdermal oestradiol groups. Tibolone decreased serum Lp(a) by 36.6% after 24 months (95% CI 8.3-56.2), oral oestradiol decreased levels by 29.4% (95% CI 2-51.1), compared with no change in the transdermal oestradiol group. CONCLUSIONS: Oral and to a lesser extent transdermal oestradiol when sequentially combined with dydrogesterone, showed a beneficial influence on serum lipids regarding the cardiovascular disease risk, which was not seen with tibolone. The significance of Lp(a) levels on cardiovascular disease risk remains to be determined.

Administration, Cutaneous

Production of endometrial placental protein 14 and prolactin by cultured endometrial explants after collagenase and freeze/thaw treatment, and in response to progesterone.

OBJECTIVE: Investigation of methods for maintaining functional endometrial explants in culture after cryopreservation with or without previous enzymatic dispersion of stromal cells and epithelial glands. Such a standardized culture system is a requirement for the development of a non-invasive bioassay for embryo quality in in vitro fertilization programs, a method that will eventually measure endometrial response to embryo conditioned media. METHOD: Culture of mid-luteal phase endometrial biopsies, in the presence of [35S]methionine, with or without prior collagenase treatment and/or storage in liquid nitrogen in the presence of dimethyl sulfoxide. Determination of released de novo synthesized total protein by trichloroacetic acid precipitation of culture media. Measurement, after culture in absence and presence of progesterone, of prolactin and placental protein 14 (PP14) production by sensitive non-isotopic immunoassays. RESULTS: Production of prolactin, but not PP14, was increased by 200 nmol/l progesterone, 2-8-fold after 4 days and 1.5-700-fold after 7 days in culture. After limited collagenase treatment (but without separation of stromal cells from glands), both marker protein productions were similar compared to untreated explants; however, there was no significant stimulation of prolactin by progesterone. After freezing and thawing, production was markedly reduced, particularly from explants frozen following collagenase treatment. CONCLUSIONS: Both stromal and glandular viability are maintained after collagenase treatment but the response to progesterone is lost. Cryopreservation reduced prolactin and PP14 production in subsequent culture. Therefore, novel freezing protocols should be developed which preserve both endometrial structure and function.

Collagenases

Benefits of different routes of administration.

The benefits of hormone replacement therapy (HRT) are well established for the different systemic administration routes used today. Relief from somatic and vasomotor postmenopausal symptoms can be obtained by all recognized forms of HRT. The prophylactic action of peroral and percutaneous administration of HRT on postmenopausal bone loss is identical if the appropriate protective dosage of the estrogen component is chosen for each galenic form. The second metabolic benefit of HRT, the cardioprotective effect of ERT, is well accepted for the peroral route. New data on the direct effect of estradiol on the arterial wall as well as recent serum lipid results obtained during percutaneous administration of estradiol in postmenopausal women allow the conclusion that the percutaneous route induces cardioprotection similar to that obtained with the classical peroral route. This opinion is supported by animal data. Furthermore, observations in animals suggest that the benefits of ERT are not neutralized by either sequential or fixed addition of progestin to the estrogen. Except in some rare cases with a particular indication for either the peroral or the percutaneous administration of HRT, the choice of route of administration should be made on the basis of maximum acceptability by the patient.

Cardiovascular Diseases

[Homologous intrauterine insemination as a therapeutic possibility in andrologically-induced sterility].

In a two-years period, we treated 58 infertile couples for a total of 213 cycles with artificial homologous insemination (AIH). We considered a indication for AIH low sperm quality or a pathological postcoital test (PCT). Couples with idiopathic infertility did not receive AIH. If possible, AIH was performed by intrauterine insemination (IUI), following concentration of the motile sperms by "swim-up" method. Out of 213 cycles "swim-up", preparation could not be done in 46 cases (21.6%) because the initial sperm quality was below technical limits (sperm count below 1 Mio/ml). Out of 58 treated couples 4 became pregnant during AIH therapy (7%) among, them 2 couples conceiving twice after spontaneous early abortion. The total pregnancy rate per cycle was 2.8%. In the cycles after "swim-up", the monthly pregnancy rate through IUI was 3.6%. In the presence of andrological factors was the pregnancy rate only 0.9% compared to 6.8% in cases of pathological PCT with normal sperm quality. Thus, it can be concluded, that IUI is not successful on the basis of low sperm quality. Only in cases of unfavourable cervical factor expressed by a pathological PCT accompanied with a normal spermiogramm, moderate success can be expected.

Adult

[Cyclical gestagen (MPA) supplement for continuous transdermal or oral estrogen substitution in postmenopause: modification of serum lipids].

Since postmenopause unopposed oestrogen replacement therapy (ERT) increases the incidence of endometrial carcinoma, the addition of a progestin in non-hysterectomised women is mandatory for hormonal substitution. On the other hand, progestins have a negative influence on serum lipids and may thus put in question the benefits of the ERT with regard to the cardiovascular risk. Progestins lower HDL and increase LDL in a dose-dependent way according to their chemical structure. In the present non-randomised study, the influence of a cyclic combined oestrogen progestin substitution on the serum lipids has been measured. From a total of 90 apparently healthy postmenopausal patients, 59 received a transdermal ERT with 17 beta-Estradiol (Estraderm TTS 50), whereas 31 women obtained a daily dose of 0.625 mg conjugated equine oestrogens (CE) perorally. Additionally all patients were given 10 mg medroxyprogesterone-acetate (MPA) daily during the first 10 days of each month. After 6 months of therapy, the following changes of serum lipids, expressed as percentage of initial values, were measured: total cholesterol in the transdermal group -2.3% (n.s.), in the peroral group -11.8% (p < 0.00001); triglycerides -3.7% (n.s.) resp. +8.6% (n.s.); HDL cholesterol + 0.2% (n.s.) resp. -1.8% (n.s.); LDL cholesterol +1.3% (n.s.) resp. -14.8% (p < 0.00001). The calculated atherogenic indices showed a decrease in the peroral substituted group of -6.5% (n.s.) for the HDL/total cholesterol ratio and -14.8% (p < 0.002) for the LDL/HDL ratio.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous

[Is the cryopreservation of sperm of young tumor patients reasonable?].

Operation, retroperitoneal lymphadenectomy, irradiation and chemotherapy may reduce the fertility potential of young male patients suffering from a malignant tumour. Prediction of the reversibility is difficult. Cryopreservation is a possibility to maintain the fertility of such patients. Unfortunately, the quality of the sperm is often reduced beforehand. The sperm motility is noticeably reduced by the freezing process. But the sperm preservation may help to reduce the psychological stress of the patients, thus improving their quality of life. Therefore, we recommend the use of the method liberally, although only few patients will make use of their sperm later. There has been no known teratogenicity to date. We report on our own experience with cryopreservation in 39 patients.

Adult

[Endocrine active genital tumors].

Endocrinically active genital tumors are indeed rare; however, their correct classification and treatment is rather difficult. If ovarian tumors coincide with abnormal hormonal activity, thorough consideration of differential diagnosis is necessary. The WHO has agreed upon a classification of endocrinically active ovarian tumors. This grouping, which is internationally accepted, is the base of the explanations, and to these, remarks about uterine HCG-producing trophoblast diseases are added. Symptomatology of endocrinically active ovarian tumors is nonuniform, depending on the tissular origin of the tumor and the pattern of its endocrine activity. Prognosis is also quite variable. This must be taken into account for therapy. E.g., operative therapy with conservation of fertility is possible--in particular in young women--with granulosa cell tumors or androblastomas; dysgerminomas are strikingly sensitive to irradiation; chorion carcinomas respond well to chemotherapy. More difficult are clear therapeutic recommendations for the very rare forms of endocrinically active genital tumors which stem from sex cords or which are composed of different components of the complex ovarian blastema. In a supplement, the relevant literature (121 quotations) is cited.

Female

[Induction of follicle maturation with "pure" FSH in polycystic ovary syndrome].

The Polycystic Ovary Syndrome (PCO) is characterised by an elevated ratio of serum LH to FSH in presence of an intrafollicular deficiency of FSH activity. Ovulation induction by "pure" FSH seems therefore a reasonable approach to longstanding chronic anovulation in infertile patients suffering from PCO. 68 treatment cycles have been conducted in 30 patients with PCO and chronic clomiphene-resistant anovulation. Ovulation has been induced by HCG in 57 of the 68 cycles. The pregnancy rate was 58.6% per patient, the success rate 46.7% per patient. Clinical abortions occurred in 17.6% of the pregnancies obtained. 3 twins and 2 triplets have been delivered at term. A hyperstimulation syndrome (HSS) of grade I (WHO) has been observed in 19.1%, a HSS of grade II (WHO) in 8.8% of the treatment cycles. 46.3% of the 54 analysed cycles presented a premature LH-surge leading to an atresia of the dominant follicle. Considering the high incidence of a premature elevation of endogenous LH, an additional administration of exogenous LH should be avoided. This consideration as well as the good success rate in the present series speak in favour of using "pure" FSH for induction of follicular maturation in clomiphene-resistant PCO.

Adult

[Hypogonadism in males and females].

This comparison of the common and distinctive signs of male and female hypogonadism is intended to acquaint the non-specialist practitioner with some general trends in andrology and gynecologic endocrinology. The author deliberately omits any presentation of rare clinical entities or precise guidelines for investigation and treatment of infertility.

Age Factors