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Biomedical subjects

M H Birkhaeuser

Publications and source records attributed to M H Birkhaeuser.

10 recordsLinked to original sources

Decrease of serum endothelin levels with postmenopausal hormone replacement therapy or tibolone.

Endothelin is the most potent vasoconstrictor peptide known to date. Hormone replacement therapy (HRT) with estrogen reduces plasma endothelin levels. We measured endothelin in 51 postmenopausal patients before and during HRT. Patients were randomly allocated to receive either oral tibolone, oral or transdermal 17 beta-estradiol. A group of comparable volunteers served as controls. After 24 months, endothelin levels decreased in all treatment groups: tibolone, 18.2%; oral 23.1%; transdermal, 20.8%. Endothelin levels increased in the controls by 36.6% (p < 0.01). Tibolone decreases endothelin levels to a similar degree as conventional estrogen-progestogen-replacement therapy. These data provide another potential mechanism supporting the cardioprotective effects of tibolone.

Administration, Cutaneous↗

CA-125 concentrations in the serum and pregnancy outcome in IVF cycles.

PURPOSE: CA-125 has been proposed as a potential marker for endometrial receptivity in assisted reproduction. This study was designed to evaluate whether the levels of CA-125 in the serum of patients undergoing IVF-embryo transfer (ET) is correlated with the outcome. METHODS: Levels of serum CA-125 were measured on the day before and on the day of human chorionic gonadotropin (hCG) administration, ovum pickup (OPU), and ET in 74 patients undergoing 100 IVF cycles between January 1994 and March 1995. Patients were treated with a midluteal-phase gonadotropin-releasing hormone (GnRH) agonist protocol and follicular-phase human menopausal gonadotropin. RESULTS: One hundred oocyte retrievals resulted in 91 ETs, and 22 clinical pregnancies (22%/OPU and 24.2%/ET). The live-born rate was 21%/OPU and 23.1%/ET. Neither the CA-125 serum levels nor their increase from the day of hCG until the day of ET showed any prognostic significance to the outcome of IVF, and they were not correlated with the endometrium thickness or the number of oocytes retrieved or fertilized. CONCLUSIONS: The CA-125 serum levels in conventional IVF cycles were not correlated with the IVF outcome and yielded no prognostic information in a GnRH agonist down-regulation protocol.

Adult↗

Prevention of postmenopausal bone loss using tibolone or conventional peroral or transdermal hormone replacement therapy with 17beta-estradiol and dydrogesterone.

Postmenopausal bone loss can be prevented by continuous or intermittent estradiol (E2) administration. Concomitant progestogen therapy is mandatory in nonhysterectomized women to curtail the risk of endometrial hyperplasia or cancer. However, the recurrence of vaginal bleeding induced by sequential progestogen therapy in addition to continuous estrogen administration is one of the reasons for noncompliance to hormone replacement therapy (HRT). Tibolone, a synthetic steroid with simultaneous weak estrogenic, androgenic, and progestational activity, which does not stimulate endometrial proliferation, has recently been proposed for the treatment of climacteric symptoms. To compare the efficacy of conventional oral and transdermal HRT with that of tibolone in the prevention of postmenopausal bone loss, 140 postmenopausal women (age, 52 +/- 0.6 years; median duration of menopause, 3 years) were enrolled in an open 2-year study. Volunteers had been offered a choice between HRT and no therapy (control group, CO). Patients selecting HRT were randomly allocated to one of the following three treatment groups: TIB, tibolone, 2.5 mg/day continuously, orally; PO, peroral E2, 2 mg/day continuously, plus sequential oral dydrogesterone (DYD), 10 mg/day, for 14 days of a 28-day cycle; TTS, transdermal E2 by patch releasing 50 microg/day, plus DYD as above. Bone densitometry of the lumbar spine, upper femur, and whole body was performed using dual-energy X-ray absorptiometry at baseline, and then 6, 12, 18, and 24 months after initiation of therapy. One hundred and fifteen women (82%) completed the 2 years of the study. The dropout rate was similar in each group. Over 2 years, bone preservation was observed in all three treatment groups as compared with controls, without significant differences among treatment regimens. In conclusion, tibolone can be regarded as an alternative to conventional HRT to prevent postmenopausal bone loss.

Absorptiometry, Photon↗

Placental protein 14 (PP14) does not predict endometrial status under hormone replacement therapy.

Our objective was to compare serum level of placental protein 14 (PP14) with histological findings in endometrial evaluation of postmenopausal women using hormone replacement therapy (HRT). In a subset of 109 out of 140 women included in a randomized comparative study, serum levels of PP14 were determined after 12 months of use of (1) no HRT; (2) oral micronized 17 beta-estradiol/oral sequential dydrogesterone; (3) transdermal 17 beta-estradiol/oral sequential dydrogesterone; or (4) oral tibolone. Subjects underwent Pipelle biopsy after 12 months. The serum level of PP14 was determined by sandwich enzyme immunoassay (ELISA). The two-tailed t-test and one-way ANOVA or their non-parametric equivalents were used to test for statistical significance. All three HRT regimens were safe with respect to the endometrium. Hyperplastic or malignant changes were not observed. There was a significant difference in the mean values of PP14 between the groups of inactive/atrophic and secretory endometrium (p < 0.01). However, there was a wide range of individual values for PP14 within the groups and a wide overlap in values between the groups of non- substituted and hysterectomized women. The quantitative determination of PP14 in the serum did not provide supplementary information on the substituted endometrium. From this study it can be concluded that the serum PP14 determination is not useful to predict endometrial status under HRT. The relatively high levels of PP14 in hysterectomized patients suggest ectopic production.

Biopsy↗

Microscopic findings of the nail-fold capillaries--dependence on menopausal status and hormone replacement therapy.

The aim of our controlled study was to evaluate peripheral microcirculation at the level of the nail-fold capillaries in relation to menopause status and postmenopausal hormone replacement therapy (HRT). A total of 105 postmenopausal women were randomly allocated to three different HRT groups of equal size. A fourth group of 35 similar healthy volunteers served as controls. HRT was either peroral or transdermal 17-beta-oestradiol with cyclic addition of dydrogesterone or 2.5 mg Tibolone (Org OD 14) in a daily peroral dose. Morphological parameters such as capillary diameters, loop width, papillary width and capillary density, measured by video-capillaroscopy at the nail-fold, were unaffected in early menopause and also under HRT. A significant decrease of capillary blood flow velocity (P < 0.001) could be demonstrated in postmenopausal (n = 41, v = 0.53 +/- 0.16 mm/s) as compared to premenopausal women (n = 37, v = 0.65 +/- 0.15 mm/s). HRT resulted in an increase of capillary blood flow velocity in the nail-fold after 6 and 12 months leading to an increase in capillary blood flow in the order of 20%-30% of the initial values, and was independent of the type of HRT.

Administration, Cutaneous↗

Bone mineral density in young women with long-standing amenorrhea: limited effect of hormone replacement therapy with ethinylestradiol and desogestrel.

To assess bone mineral density (BMD) at different skeletal sites in women with hypothalamic or ovarian amenorrhea and the effect of estrogen-gestagen substitution on BMD we compared BMD of 21 amenorrheic patients with hypothalamic or ovarian amenorrhea with that of a control population of 123 healthy women. All amenorrheic patients were recruited from the outpatient clinic of the Division of Gynecological Endocrinology at the University of Berne, a public University Hospital. One hundred and twenty-three healthy, regularly menstruating women recruited in the Berne area served as a control group. BMD was measured using dual-energy X-ray absorptiometry (DXA). At each site where it was measured, mean BMD was lower in the amenorrheic group than in the control group. Compared with the control group, average BMD in the amenorrheic group was 85% at lumbar spine (p < 0.0001), 92% at femoral neck (p < 0.02), 90% at Ward's triangle (p < 0.03), 92% at tibial diaphysis (p < 0.0001) and 92% at tibial epiphysis (p < 0.03). Fifteen amenorrheic women received estrogen-gestagen replacement therapy (0.03 mg ethinylestradiol and 0.15 mg desogestrel daily for 21 days per month), bone densitometry being repeated within 12-24 months. An annual increase in BMD of 0.2% to 2.9% was noted at all measured sites, the level of significance being reached at the lumbar spine (p < 0.0012) and Ward's triangle (p < 0.033). In conclusion BMD is lower in amenorrheic young women than in a population of normally menstruating, age-matched women in both mainly trabecular (lumbar spine, Ward's triangle, tibial epiphysis) and mainly cortical bone (femoral neck, tibial diaphysis).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Kallmann syndrome and associated malformation of the uterus.

Kallmann syndrome is a rare combination of hypogonadotropic hypogonadism due to hypothalamic insufficiency and anosmia. In both patients treated at our institution for infertility, a malformation of the uterus was noted: one patient had a unicornuate uterus, the other a uterus with a fundal hypoplasia and tubes of approximately 9 cm. It is not clear if the malformation is in association with Kallmann syndrome or purely coincidental. Given the known association of other malformations with Kallmann syndrome, we suppose that probably an underlying genetic defect having to do with organogenesis is the cause of the uterine malformations.

Adult↗

A new peroral estrogen/progestin combination for postmenopausal hormonal substitution: an open multicentric field study.

An open prospective multicentric trial has been conducted over 6 months in 241 postmenopausal volunteers. One-hundred forty-one women had an intact uterus. All patients received a fixed peroral combination of conjugated estrogens CE (1.25 mg per day from day 1 to day 21) and medrogestone (5 mg per day from day 12 to day 21) followed by 7 days without substitution (day 22 to day 28). After 3 months of treatment, the managing physician could, according to the patient's clinical response, reduce the dosage of CE to 0.625 mg daily. This dose reduction took place in 79 patients (38.9%). The trial was designed to study efficacy, compliance and side-effects of this combination. Of the patients 68.9% showed a very good, 27.7% a good and 1.9% a satisfactory improvement of their preexisting subjective complaints. Of the patients 28.6% suffered from minor side-effects leading to drop-outs in 7.8% of the cases. Of the women participating in the study 92.2% completed the trial without from the treatment scheme. No serious complications have been noted. After 6 months of treatment, a regular bleeding pattern has been observed in 71.5% of the 144 non-hysterectomized women, an irregular pattern in 9.7% and amenorrhoea in 18.8%. Total cholesterol showed no change, whereas HDL rose significantly from 1.58 to 1.72 mmol/l (P < 0.01) resulting in a drop of Total-Cholesterol-HDL-Ratio of -8.8% (P < 0.01). LDL decreased from 3.71 +/- 1.56 to 3.45 +/- 1.39 (P < 0.05). Considering the two patient groups with and without estrogen reduction after 3 months, HDL increase was significant in both groups but was dose dependent. The HDL increase compared to the initial value was 5.7% with 0.625 mg CE and +10.8% with 1.25 mg CE, respectively. The fixed peroral combination of CE and medrogestone tested was effective, easy to administer and safe. The bleeding pattern observed was mostly regular. The pattern of serum lipids changed favorably in a significant way. Therefore, the use of this new peroral estrogen/progestin combination can be recommended for routine substitution in postmenopausal women.

Blood Pressure↗

Postmenopausal hormone replacement therapy with Tibolone decreases serum lipoprotein(a).

Lipoprotein(a) is a cholesterol-rich plasma lipoprotein consisting of LDL and apolipoprotein(a). Apolipoprotein(a) shows structural similarity with plasminogen and thus may interfere with thrombogenesis. Lipoprotein(a) has been shown to be a strong independent risk factor for coronary heart disease. So far no drug or diet is known to have prominent effects on the serum levels of lipoprotein(a). In the present study we found a highly significant decrease (in the order of 26%) of lipoprotein(a) in 28 women treated for 6 months with Tibolone, compared with an age-matched healthy control group. Tibolone is a synthetic steroid with gestagenic and weak androgenic and oestrogenic properties, which shows no stimulation of the endometrium. Tibolone also produced a decrease in HDL-cholesterol of 23% (p < 0.001), a decrease in apolipoprotein A-I of 14% (p < 0.001) and an increase in apolipoprotein B of 17% (p < 0.001), whereas the control group showed no significant changes in these quantities. Tibolone in a daily dose of 2.5 mg is at present the only complete postmenopausal hormone replacement therapy that shows a significant inhibiting influence on serum levels of lipoprotein(a). Its effect on lipoprotein(a) might counterbalance, at least to some extent, the theoretical adverse effect on the other lipoprotein risk factors.

Anabolic Agents↗