Transdermal progesterone and its effect on vasomotor symptoms,blood lipid levels,bone metabolic markers,moods, and quality of life for postmenopausal women

OBJECTIVE: To determine whether transdermal progesterone cream has any effect on vasomotor symptoms, mood, sexual response, cardiovascular lipid levels, or bone mineral metabolic markers. DESIGN: A parallel, double-blind, randomized, placebo-controlled trial comparing the effect of a transdermal cream containing a progesterone (32 mg daily) with a placebo cream. Eighty postmenopausal women in the Menopause Centre at the Royal Hospital for Women, Sydney, were randomly allocated to receive either the progesterone cream or the placebo. They were evaluated using the Greene Climacteric Scale and the Menopause Quality of Life Questionnaire, as well as blood analysis for lipids and bone markers over a period of 12 weeks. Women were prescribed a cream containing either progesterone at 32 mg daily or a placebo cream for a period of 12 weeks. RESULTS: There was no detectable change in vasomotor symptoms, mood characteristics, or sexual feelings, nor was there any change in blood lipid levels or in bone metabolic markers, despite a slight elevation of blood progesterone levels. CONCLUSION: The use of the transdermal route to administer progesterone at 32 mg daily does not seem to allow sufficient hormone to enter the body to achieve a biological effect on lipid levels, bone mineral metabolic markers, vasomotor symptoms, or moods.     

How to use Chlamydia antibody testing in subfertility patients

Screening for tubal factor subfertility by means of Chlamydia antibody testing (CAT) was introduced into the initial work-up of subfertile couples several years ago. The results reported, however, are heterogeneous, and no uniformity exists in cut-off levels of titres, or in definitions of tubal factor subfertility. We performed a prospective cohort study to evaluate the implications of varying the definitions of tubal pathology and of modifying the cut-off levels on the clinical impact of CAT in predicting tubal factor subfertility. In 227 consecutive patients who attended our fertility clinic, the Chlamydia IgG antibody titre was determined and related to tuboperitoneal abnormalities at laparoscopy as a reference standard. According to received operating characteristic (ROC) curve analysis, a titre of 16 is the optimum cut-off level. Increasing the cut-off level improves specificity and positive likelihood ratio (LR+), at the expense of sensitivity and negative LR (LR-). Changing the definition of tubal factor subfertility from unspecified tuboperitoneal abnormalities into extensive adhesions and/or bilateral distal tubal occlusion improves LR+, LR- and kappa significantly. We conclude that CAT is more accurate in predicting severe distal tubal pathology than unspecified tuboperitoneal abnormalities. Although from a statistical point of view a titre of 16 is the optimum cut-off level, from a clinical point of view 32 or 64 may be preferable, depending on the aim of screening and the inception cohort.      

Anxiety during pregnancy and fetal attachment after in-vitro fertilization conception

The aim of this study was to compare 70 couples who had conceived by in- vitro fertilization (IVF) with 63 matched controls for the prevalence of anxiety and quality of attachment to the baby during pregnancy. Results for mothers showed no group differences using a global measure of anxiety, the Spielberger State-Trait Anxiety Inventory. However, pregnancy-specific measures revealed significantly higher levels of anxiety in IVF mothers about the survival and normality of their unborn babies, about damage to their babies during childbirth and about separating from their babies after birth. When IVF mothers were differentiated according to the number of treatment cycles, more differences in anxiety level were revealed, with most increases occurring in mothers who had experienced two or more treatment cycles. IVF fathers did not differ from controls on the global anxiety measure. No data on pregnancy-specific anxiety were available for fathers. Neither IVF mothers nor IVF fathers differed from controls on measures of attachment to the baby during pregnancy. Results are discussed in the context of the need for researchers to employ differentiated and issue-specific measures to identify concerns that may be unique to IVF couples. Clinical implications regarding the need for psychological support during pregnancy are also discussed.      

Partial trisomy 6p and partial monosomy 9p from a de novo translocation 46, XY, -9, + DER(9)T(6:9)(p211:p24)

This report describes an adult male with a partial trisomy 6p(p211-pter) and a partial monosomy 9p(9p24-pter) resulting from a de novo unbalanced translocation. This patient does not show the classical featured of the 9p partial monosomy syndrome, thus disputing the claim of Hoo et al. (1982) that 9p24 is the critical segment for the monosomy syndrome. Partial trisomy for 6p has only been previously reported in children. In addition to the chromosomal anomalies, the patient has autosomal recessive spinal muscular atrophy with a different age of onset than two affected sibs. Finally, he shows unusual audiologic and ophthalmologic signs nor previously reported as part of the 9p monosomy or 6p trisomy syndromes.     

Generation and characterization of a clonotypic antibody specific for the T cell receptor of an arthritogenic T cell clone--studies in adjuvant arthritis

Adjuvant Arthritis (AA) can be induced by passive transfer of a T cell clone (A2b) derived from arthritic rats, specific for Heat Shock Protein 60, HSP60 176-190. Furthermore, a crucial role for T cells with HSP60 176-190 specificity in AA was shown by induction of tolerance using HSP60 176-190 or by immunization with an altered peptide ligand based on the same sequence. To study clonal expansion of A2b-like T cells during AA and to determine their role in AA induction, we generated a clonotypic antibody, 16C4, specific for the TCR of the A2b T cell clone (TCR AV11S1/BV18). This antibody stained A2b T cells in flow cytometry experiments, induced proliferation of A2b cells when fixed on a solid support, and inhibited antigen-induced A2b proliferation when added in solution. A2b-like T cells were detected in a low frequency in lymphoid organs of arthritic rats. Thus, as in vivo administration of 16C4 did not inhibit AA, cells containing the determinant recognized by 16C4 are possibly not the sole contributors to AA development. Furthermore, epitope specific interventions by antigen administration may be possible even in cases where the epitope specific T cell clonotype is of low frequency.     

Antiphospholipid antibodies and the outcome of pregnancy after the first in-vitro fertilization and embryo transfer cycle

Increased antiphospholipid antibody prevalence has been demonstrated by a number of recent studies in in-vitro fertilization (IVF) patients but the potential effects of antiphospholipid antibodies on the different components of the reproductive process and the consideration of whether to test IVF patients for antiphospholipid antibodies are controversial. The present study was undertaken to investigate the possible association between the presence of circulating antiphospholipid antibodies (namely the lupus anticoagulant and anticardiolipin antibodies), among a series of 21 consecutive IVF patients having a clinical spontaneous abortion after their first embryo transfer. As a control group (n=42), the nearest IVF cycle resulting in an ongoing pregnancy before and after each miscarried IVF cycle (i.e. the closest cycles in temporal relationship to the index cycle) was used. One patient (4.8%) in the study group and two women (4.8%) among controls were seropositive for antiphospholipid antibodies. These low and similar seropositivity rates found in the two groups studied lead us to conclude that antiphospholipid antibodies testing in IVF patients should be considered only in those women having repeated failures of implantation/clinical abortion after embryo transfer but not in an infertile general population reaching an IVF programme.      

Assessment of bioequivalence after subcutaneous and intramuscular administration of urinary gonadotrophins

The objective was to demonstrate bioequivalence between s.c. and i.m. administration of Humegon (FSH/LH ratio 1:1) and Normegon (FSH/LH ratio 3:1). In two randomized, single-centre, cross-over studies, 18 healthy volunteers on each formulation were assigned to one of the two administration sequences. Subjects were given single doses of one of the above gonadotrophins after endogenous gonadotrophin production had first been suppressed using high-dose oral contraceptive. Subsequently, rate (Cmax, tmax) and extent (AUC) of absorption of follicle stimulating hormone (FSH) and luteinizing hormone (LH) were determined for 14 days. For Cmax and AUC, analysis of variance (ANOVA) was performed on log-transformed data and for tmax ANOVA was performed on ranks. Intramuscular and s.c. injections of Humegon were bioequivalent with respect to the main pharmacokinetic parameters, being AUC and Cmax of FSH absorption. Intramuscular and s.c. injections of Normegon were bioequivalent with respect to the AUC of FSH and not bioequivalent with respect to the Cmax of FSH. For tmax of FSH as well as for most LH variables of both preparations, bioequivalence could not be proven due to the high intra- and interindividual variability and/or concentrations being close to the detection limit. Thus, the main pharmacokinetic FSH variables after i.m. and s.c. administration of Humegon and Normegon were bioequivalent.