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Information about the topics discussed at the International Menopause Society (IMS) global summit on issues related to menopause is presented. Attendees agreed on the significant role of quality of life in menopause management. They also talked about the benefits and risks of hormone replacement therapy (HRT). Additionally, they examined perceptions and scientific evidences of HRT.

Objectives To determine whether the serum levels of pregnancy-associated plasma protein A (PAPP-A), pregnancy-specific β1-glycoprotein (SP1), placental lactogen (hPL) and human chorionic gonadotrophin (hCG) are different in pregnancies obtained after in vitro fertilisation (IVF) and embryo transfer (ET) in comparison to spontaneous pregnancies. Assessment of the need to establish normal medians for biochemical trisomy screening in IVF pregnancies. Methods The population comprised 96 IVF-ET pregnancies, of which 79 came from fresh gonadotrophin-stimulated cycles and 17 from embryo transfers without gonadotrophin stimulation (natural cycle IVF, frozen embryo transfers), and 156 spontaneous pregnancies. A single blood sample was obtained between 7 + 0 and 16 + 3 weeks. PAPP-A, SP1, hPL and hCG were quantified and the levels compared between gonadotrophin-stimulated IVF, steroid-only- or non-stimulated IVF, and controls with respect to gestational age using non-parametric statistical analysis. Results PAPP-A and hPL levels were reduced after stimulated IVF in early gestation (before 10 pregnancy weeks); SP1 followed the same trend without reaching statistical significance. hCG tended to be increased after IVF treatment including non-gonadotrophin-stimulation cycles, and also beyond 10 pregnancy weeks. Conclusion Reduced PAPP-A with increased hCG yields an increased risk in screening for foetal trisomy 21. We confirm recently published observations but do not recommend the establishment of normal medians for IVF pregnancies since the extent of the deviations is varying according to the different stimulation protocols and dosages of gonadotrophins used. Copyright © 2004 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

In the last decade, several reports suggest that oestrogen replacement therapy (ORT=ERT=estrogen replacement therapy) might prevent or delay Alzheimer's disease. Oestrogens influence and modulate brain structure and brain function. There are substantial arguments that the postmenopausal oestrogen loss might, together with other factors, accelerate the appearance of Alzheimer's disease. The evidence is suggestive, but not compelling, that ORT can reduce the relative risk to suffer from Alzheimer's disease. Furthermore, recent findings are consistent with the hypothesis that oestrogens might ameliorate the symptomatology in early stages of Alzheimer's disease. However, it has to be remembered that in most clinical trials the number of oestrogen users was quite small, and, usually, oestrogen use was not randomised. The aim of the present review is to discuss the data available today in view of their clinical relevance. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Hyperglycosylated human chorionic gonadotropin (H-hCG) is secreted by the placenta in early pregnancy. Decreased H-hCG levels have been associated with abortion in spontaneous pregnancy. We retrospectively measured H-hCG and dimeric hCG in the sera of 87 in vitro fertilization patients obtained in the 3 weeks following embryo transfer and set the results in relation to pregnancy outcome. H-hCG and dimeric hCG were correlated (r(2) = 0.89), and were significantly decreased in biochemical pregnancy (2 microg/l and 18 IU/l, respectively) compared to early pregnancy loss (22 microg/l and 331 IU/l) and ongoing pregnancy (32 microg/l and 353 IU/l). Only H-hCG tended to discriminate between these last two groups., (Copyright 2008 S. Karger AG, Basel.)

Background: The objective of this study was to compare cycle control, cycle-related characteristics and bodyweight effects of NuvaRing with those of a combined oral contraceptive (COC) containing 30 microg of ethinyl estradiol and 3 mg of drospirenone., Methods: A randomized, multicentre, open-label trial in which 983 women were treated (intent-to-treat population) with NuvaRing or the COC for 13 cycles., Results: Breakthrough bleeding or spotting during cycles 2-13 was in general less frequent with NuvaRing than that with the COC (4.7-10.4%) and showed a statistically significant odds ratio of 0.61 (95% confidence interval: 0.46, 0.80) with longitudinal analysis. Intended bleeding was significantly better for all cycles with NuvaRing (55.2-68.5%) than that with the COC (35.6-56.6%) (P < 0.01). Changes from baseline in mean bodyweight and body composition parameters were relatively small for both groups with no notable between-group differences., Conclusion: NuvaRing was associated with better cycle control than the COC, and there was no clinically relevant difference between the two groups in bodyweight.

Background: Several studies have investigated seasonal variations during IVF. Their results are contradictory, especially concerning fertilization and pregnancy rates. The aim of the present study was to re-evaluate these parameters using a large number of IVF cycles., Methods: A total of 7368 IVF cycles conducted in Switzerland between 1995 and 2003 were retrospectively analysed. To avoid a bias in the evaluation of the fertilization rate, only IVF cycles without ICSI were considered for analysis. Cycles were assigned to seasons according to the date of the beginning of stimulation., Results: There were no statistically significant differences between the seasons concerning the fertilization, the pregnancy and the implantation rates. However, statistically significant variables deciding on the outcome of an IVF cycle are age, centre, aetiology of infertility and day of transfer., Conclusions: There were no statistically significant seasonal differences in central Europe (Switzerland) that influenced the outcome of IVF treatment. The only statistically significant variables of IVF outcome were age, centre, aetiology of infertility and day of transfer. A change to routine fertility treatment concerning the different seasons should therefore not be taken into account.

Postmenopausal primary ovarian insufficiency may lead to the clinical picture of the climacteric syndrome and to metabolic changes inducing specific diseases due to oestrogen deficiency. In symptomatic states of oestrogen deficiency, Hormone Replacement Therapy (HRT) is indicated for therapeutic reasons. If there is an increased risk for osteoporosis, for cardiovascular diseases or for Alzheimer's Disease, the preventive administration of HRT has to be discussed. In the combined presence of an increased metabolic risk and of subjective symptoms, HRT is still the best choice. Recent alternatives to classical HRT are Tibolone and, in the later postmenopause, Raloxifene. Incorrect media reports lead to insecurity and to concerns about the use of sexual steroids after menopause. HRT can be accompanied by a small weight increase of 200-500 g. However, more important in most women is the normal trend to weight gain in the 40s and 50s. HRT does not increase blood pressure. If there are some hints for an abnormal coagulation system in the personal or family history of a patient, thrombophilia should be excluded before the begin of HRT. The risk to have an endometrial carcinoma during HRT is not increased, but endometrial cancers are more frequent with unopposed estrogen administration. The incidence of breast cancer increases continuously with ageing. If 1000 women start HRT at the age of 50 and continue for five years, two more cases of breast cancer are diagnosed within the next 20 years. This small increase of morbidity is not accompanied by an increased mortality due to breast cancer: mortality does not change. The data available today show a clear decrease of total mortality up to the age of 75 years in women using oestrogens and speak in favour of HRT. If HRT is used for less than five years, cancer risk is not increased. The gain in Life Quality primes significantly. For the indication of long term HRT, the risks and benefits have to be evaluated individually.

Family and personal history as well as clinical examination are the basic data to be known before laboratory examinations should be started. To obtain results that can be correctly interpreted, the blood sampling has to be done in the early morning hours between day 1 and 5 of the cycle, and for some hormones on an empty stomach. Depending on the clinical data, the hormonal screening can be selective and well directed, or it has to be broader. The presence or absence of galactorrhea, of hot flushes and of androgenization or virilization play an important role for the decision about the hormones to be determined. Furthermore, an eventual desire infertility will influence the selection of the hormonal tests to be done. The present review intends to propose some simple recommendations to the non-specialist how a gynaecological-endocrinological screening for the most important clinical questions should be organized.

Pregnancy-associated plasma protein A (PAPP-A) was found to be a good first trimester maternal serum marker, together with free beta-human chorionic gonadotrophin (HCG) subunits, for the biochemical screening of fetal trisomy 21 (Down's syndrome). We have raised monoclonal antibodies (mAbs) against PAPP-A purified from human pregnancy serum. The different antibodies were characterized biochemically by Western blot analysis and in terms of specificity (reaction with non-pregnant and male serum). Their performance in Down's syndrome screening was assessed in comparison with an existing enzyme-linked immunosorbent assay method after labelling of the different mAbs with biotin or horseradish peroxidase. A pair of mAbs was eventually chosen for a double-antibody sandwich protocol. The selected combination was found to have a significantly increased specificity (P = 0.0116) over the method using (purified) polyclonal antibodies, together with slightly increased sensitivity. In our limited number of Down's syndrome pregnancy samples (n = 17) and controls (n = 18), the medians as well as the multiples of the median values (for the affected cases) were comparable between the two methods described.

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.

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.

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.

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.

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.

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.