Antiandrogen or estradiol treatment or both during hormone therapy in transitioning transgender women.

BACKGROUND: Gender dysphoria is described as a mismatch between an individual's experienced or expressed gender and their assigned gender, based on primary or secondary sexual characteristics. Gender dysphoria can be associated with clinically significant psychological distress and may result in a desire to change sexual characteristics. The process of adapting a person's sexual characteristics to their desired sex is called 'transition.' Current guidelines suggest hormonal and, if needed, surgical intervention to aid transition in transgender women, i.e. persons who aim to transition from male to female. In adults, hormone therapy aims to reverse the body's male attributes and to support the development of female attributes. It usually includes estradiol, antiandrogens, or a combination of both. Many individuals first receive hormone therapy alone, without surgical interventions. However, this is not always sufficient to change such attributes as facial bone structure, breasts, and genitalia, as desired. For these transgender women, surgery may then be used to support transition. OBJECTIVES: We aimed to assess the efficacy and safety of hormone therapy with antiandrogens, estradiol, or both, compared to each other or placebo, in transgender women in transition. SEARCH METHODS: We searched MEDLINE, the Cochrane Central Register of Controlled Trials (CENTRAL), Embase, Biosis Preview, PsycINFO, and PSYNDEX. We carried out our final searches on 19 December 2019. SELECTION CRITERIA: We aimed to include randomised controlled trials (RCTs), quasi-RCTs, and cohort studies that enrolled transgender women, age 16 years and over, in transition from male to female. Eligible studies investigated antiandrogen and estradiol hormone therapies alone or in combination, in comparison to another form of the active intervention, or placebo control. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane to establish study eligibility. MAIN RESULTS: Our database searches identified 1057 references, and after removing duplicates we screened 787 of these. We checked 13 studies for eligibility at the full text screening stage. We excluded 12 studies and identified one as an ongoing study. We did not identify any completed studies that met our inclusion criteria. The single ongoing study is an RCT conducted in Thailand, comparing estradiol valerate plus cyproterone treatment with estradiol valerate plus spironolactone treatment. The primary outcome will be testosterone level at three month follow-up. AUTHORS' CONCLUSIONS: We found insufficient evidence to determine the efficacy or safety of hormonal treatment approaches for transgender women in transition. This lack of studies shows a gap between current clinical practice and clinical research. Robust RCTs and controlled cohort studies are needed to assess the benefits and harms of hormone therapy (used alone or in combination) for transgender women in transition. Studies should specifically focus on short-, medium-, and long-term adverse effects, quality of life, and participant satisfaction with the change in male to female body characteristics of antiandrogen and estradiol therapy alone, and in combination. They should also focus on the relative effects of these hormones when administered orally, transdermally, and intramuscularly. We will include non-controlled cohort studies in the next iteration of this review, as our review has shown that such studies provide the highest quality evidence currently available in the field. We will take into account methodological limitations when doing so.

[Why is andrology part of dermatology]. / Warum Andrologie in der Dermatologie.

Andrology evolved more than 100 years ago in order to create an equivalent to gynecology for specific male problems in reproductive medicine. The first stimuli for the clinical and scientific development of this specialty in Germany arose from dermatologists. Andrology thus appears as a moiety of dermatology. In 2003 the visibility of andrology among the medical disciplines was accentuated by the introduction of an additional specialty specification for dermatologists, endocrinologists and urologists, since the other two disciplines also worked on andrological problems. Today, the majority of the members of the Society of Andrology are urologists and also urologists form the majority of medical practioners with this additional specialty. Besides reproductive medicine, there are several other topics which underline the conjunction of dermatology and andrology. Hence andrology should be observed as a part of dermatology not only for historical reasons. Andrology is a living subspecialty of dermatology and young dermatologists should be motivated to become engaged in it.

Methodische Anleitung für Scoping Reviews (JBI-Methodologie).

Reviews of primary research studies are becoming increasingly important as the concept of evidence-based practice in healthcare is gaining more and more influence and the number of research projects is increasing enormously. One of the less well-known types of review is the "scoping review." Scoping reviews are conducted when one first needs to take stock of the research literature. For example, scoping reviews are conducted in order to establish provisional working definitions or to define topics or subject areas conceptually. Preparing a scoping review also makes sense if the literature has not yet been comprehensively assessed or if it contains a complex or heterogeneous problem so that a more precise systematic review of the evidence is not appropriate. Scoping reviews can also serve to determine the scope and significance of a prospective classical systematic review. Finally, scoping reviews are also a good way to bundle and communicate research results, identify research gaps, and formulate recommendations for future research. This article explains the methodology of scoping reviews, their differences as compared to systematic reviews, and the reasons why they could be conducted. This guide to conducting scoping reviews is based on the methodology developed by the Joanna Briggs Institute (JBI).

The aging male--diagnosis and therapy of late-onset hypogonadism.

Managing the clinical features of hormone insufficiency in aging men is an important field of activity for dermatologists and in particular for dermatologists specialized in andrology. Potential consequences of age-associated decrease in plasma testosterone levels include long-term changes in diverse organ systems including changes of bone architecture, body composition, muscular strength, cognitive functions, and mood as well as negative effects on skin and hair. Indications and contraindications for a hormone replacement therapy as well as therapy monitoring are well-defined. Replacement of testosterone in the case of late-onset hypogonadism is not a standardized therapy. Previous studies suggest that testosterone replacement therapy has positive clinical effects. Dermatologic effects of testosterone replacement therapy have not yet been investigated. Further research is required to identify potential benefits and risks of hormone replacement therapy in aging men.

Characterization of a major secretory protein in the cane toad (Bufo marinus) choroid plexus as an amphibian lipocalin-type prostaglandin D synthase.

Here we report the enzymatic and ligand-binding properties of a major secretory protein in the choroid plexus of cane toad, Bufo marinus, whose protein is homologous with lipocalin-type prostaglandin (PG) D synthase (L-PGDS) and is recombinantly expressed in Xenopus A6 cells and Escherichia coli. The toad protein bound all-trans retinal, bile pigment, and thyroid hormones with high affinities (K(d)=0.17 to 2.00 microM). The toad protein also catalysed the L-PGDS activity, which was accelerated in the presence of GSH or DTT, similar to the mammalian enzyme. The K(m) value for PGH(2) (17 microM) of the toad protein was almost the same as that of rat L-PGDS (14 microM), whereas the turnover number (6 min(-1)) was approximately 28 fold lower than that of rat L-PGDS. Site-directed mutagenesis based on a modeled structure of the toad protein revealed that Cys(59) and Thr(61) residues were crucial for the PGDS activity. The quadruple Gly(39)Ser/Ala(75)Ser/Ser(140)Thr/Phe(142)Tyr mutant of the toad protein, resembling mouse L-PGDS, showed a 1.6 fold increase in the turnover number and a shift in the optimum pH for the PGDS activity from 9.0 to 8.5. Our results suggest that the toad protein is a prototype of L-PGDS with a highly functional ligand-binding pocket and yet with a primitive catalytic pocket.

Change in structure of the N-terminal region of transthyretin produces change in affinity of transthyretin to T4 and T3.

The relationship between the structure of the N-terminal sequence of transthyretin (TTR) and the binding of thyroid hormone was studied. A recombinant human TTR and two derivatives of Crocodylus porosus TTRs, one with the N-terminal sequence replaced by that of human TTR (human/crocTTR), the other with the N-terminal segment removed (truncated crocTTR), were synthesized in Pichia pastoris. Subunit mass, native molecular weight, tetramer formation, cross-reactivity to TTR antibodies and binding to retinol-binding protein of these recombinant TTRs were similar to TTRs found in nature. Analysis of the binding affinity to thyroid hormones of recombinant human TTR showed a dissociation constant (Kd) for triiodothyronine (T3) of 53.26+/-3.97 nM and for thyroxine (T4) of 19.73+/-0.13 nM. These values are similar to those found for TTR purified from human serum, and gave a Kd T3/T4 ratio of 2.70. The affinity for T4 of human/crocTTR (Kd=22.75+/-1.89 nM) was higher than those of both human TTR and C. porosus TTR, but the affinity for T3 (Kd=5.40+/-0.25 nM) was similar to C. porosus TTR, giving a Kd T3/T4 ratio of 0.24. A similar affinity for both T3 (Kd=57.78+/-5.65 nM) and T4 (Kd=59.72+/-3.38 nM), with a Kd T3/T4 ratio of 0.97, was observed for truncated crocTTR. The obtained results strongly confirm the hypothesis that the unstructured N-terminal region of TTR critically influences the specificity and affinity of thyroid hormone binding to TTR.

Case report: primary carcinoid tumor of the testicle without metastases in combination with testicular atrophy and testosterone deficiency.

The first case of testicular carcinoid was represented as an element of a benign cystic teratoma by Simon et al. J Urol 1954; 72: 892-894. It is a rare disease accounting for less than 1% of all testicular neoplasms. We report a case of carcinoid of the testis without carcinoid syndrome and metastasis but with testosterone deficiency based on a bilateral testicular atrophy, which has not been previously reported.

Comparison of three staining methods for the morphological evaluation of human spermatozoa.

OBJECTIVE: To compare different staining methods to evaluate human sperm morphology. DESIGN: Prospective study. SETTING: Patients at the Departments of Dermatology and Urology, University of Jena, Germany. PATIENT(S): A total of 94 randomly collected patients attending the andrological outpatient clinics of the Departments of Dermatology and Urology, University of Jena, Germany. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Statistical comparison of resultant standard morphological parameters (mean percentages) after staining according to Papanicolaou and Shorr methods and with Testsimplets prestained slides. RESULT(S): All morphological parameters investigated (percent normal morphology, percent head, midpiece, and flagellar abnormalities) correlated statistically significantly positively, however with markedly lower correlation coefficients for the Testsimplets results. As compared with the mean Papanicolaou (4.78% +/- 2.54%) and Shorr staining (4.75% +/- 2.64%) results, a statistically significantly lower percentage of morphologically normal spermatozoa was determined after using the Testsimplets slides (3.89% +/- 2.53%). In general, the mean values of all parameters differed for all comparisons with the Testsimplets slides and especially for the percentage of flagellar defects but not between the Papanicolaou and the Shorr staining results. CONCLUSION(S): The results show an extensive agreement between the Papanicolaou- and Shorr-stained smears, whereas Testsimplets staining exhibited statistically significant deviations. Because the correct evaluation of sperm morphology is of essence within the scope of assisted reproduction and in andrological diagnostics, the use of rapid staining methods cannot be recommended.

The evolution of transthyretin synthesis in the choroid plexus.

Choroid plexus has the highest concentration of transthyretin (TTR) mRNA in the body, 4.4 microg TTR mRNA/g wet weight tissue, compared with 0.39 microg in the liver. The proportion of TTR to total protein synthesis in choroid plexus is 12%. All newly synthesized TTR is secreted towards the ventricles. Net transfer of T4 occurs only towards the ventricle and depends on ongoing protein synthesis. Thyroxine-binding globulin (TBG), TTR and albumin form a "buffering" system for plasma [T4] because of their overlapping affinities and on/off rates for L-thyroxine (T4)-binding. The individual components of this network determining T4 distribution are functionally highly redundant. Absence of TBG (humans), or TTR (mice), or albumin (humans, rats) is not associated with hypothyroidism. Natural selection is based on small, inheritable alterations improving function. The study of these alterations can identify function. TTR genes were cloned and sequenced for a large number of vertebrate species. Systematic, stepwise changes during evolution occurred only in the N-terminal region, which became shorter and more hydrophilic. Simultaneously, a change in function occurred: TTR affinities for T4 are higher in mammals than in reptiles and birds. L-triiodothyronine (T3) affinities show the opposite trend. This favors site-specific regulation of thyroid hormones by tissue-specific deiodinases in the brain.

Crocodile transthyretin: structure, function, and evolution.

Structure and function were studied for Crocodylus porosus transthyretin (crocTTR), an important intermediate in TTR evolution. The cDNA for crocTTR mRNA was cloned and sequenced and the amino acid sequence of crocTTR was deduced. In contrast to mammalian TTRs, but similar to avian and lizard TTRs, the subunit of crocTTR had a long and hydrophobic NH(2)-terminal region. Different from the situation in mammals, triiodothyronine (T(3)) was bound by crocTTR with higher affinity than thyroxine (T(4)). Recombinant crocTTR and a chimeric construct, with the NH(2)-terminal region of crocTTR being replaced by that of Xenopus laevis TTR, were synthesized in the yeast Pichia pastoris. Analysis of the affinity of the chimeric TTRs showed that the NH(2)-terminal region modulates T(4) and T(3) binding characteristics of TTR. The structural differences of the NH(2)-terminal regions of reptilian and amphibian TTRs were caused by a shift in splice sites at the 5' end of exon 2. The comparison of crocodile and other vertebrate TTRs shows that TTR evolution is an example for positive Darwinian evolution and identifies its molecular mechanism.

One-dimensional spatial soliton families in optimally engineered quasi-phase-matched lithium niobate waveguides.

The advantage for quadratic soliton generation of engineering the quasi-phase-matching period near the input of lithium niobate slab waveguides is demonstrated. This approach allows members of one-dimensional quadratic soliton families with different values of the wave-vector mismatch to be cleanly excited and to be characterized by quantitative intensity-profile measurements of both the fundamental and the second-harmonic soliton components.

[Relapsing polychondritis as a rare different diagnosis of erysipelas]. / Rezidivierende Polychondritis als seltene Differentialdiagnose des Erysipels.

A 76-year old patient with painful erythematous swelling of the right ear was initially treated with antibiotics under the suspected diagnosis of erysipelas. Her failure to respond and a history of previous laryngeal and nasal swelling suggested the possibility of relapsing polychondritis. High dose prednisolone therapy produced marked improvement. Relapsing polychondritis should be considered as a rare, but important differential diagnostic consideration for erysipelas.

Developmental profile of thyroid hormone distributor proteins in a marsupial, the tammar wallaby Macropus eugenii.

The ontogeny of thyroxine distributor proteins in serum of the marsupial Macropus eugenii (tammar wallaby) was investigated from day 3 after birth until adulthood. The thyroxine distributor proteins in the serum of adult M. eugenii are transthyretin and albumin. Northern analysis of RNA prepared from liver showed that transthyretin mRNA levels were initially high (about adult levels at the earliest ages tested), reduced to about 60% adult levels (between days 50 and 150), and then steadily increased to adult levels (by days 200 to 250). Albumin mRNA levels were initially about 50% of adult levels (day 3) and steadily rose to 90% of adult levels by days 175 to 220. A globulin, "wallaby thyroxine-binding protein" (W-TBP), bound [(125)I]thyroxine from day 3 until about day 200. Of the protein-bound thyroxine, the proportion bound by transthyretin had a similar pattern to the transthyretin mRNA levels. From day 26 onward, about half of the protein-bound thyroxine was bound to albumin. On day 3, less than 10% was bound to W-TBP and the proportion steadily increased to a maximum of about 46% by about day 120 and then reduced to undetectable levels by around day 250. The developmentally regulated W-TBP was present throughout pouch life, when the pouch young is dependent on obtaining thyroxine required for normal growth and development from the mother. After the young tammar wallaby leaves its mother's pouch, a time when it has reached a level of physiological development approximately equivalent to that at the time of birth in precocious eutherian mammals such as cattle and sheep, W-TBP was no longer detected as a thyroxine distributor protein in serum.