[Beyond NICE: Updated Systematic Review on the Current Evidence of Using Puberty Blocking Pharmacological Agents and Cross-Sex-Hormones in Minors with Gender Dysphoria]. / Beyond NICE: Aktualisierte systematische Übersicht zur Evidenzlage der Pubertätsblockade und Hormongabe bei Minderjährigen mit Geschlechtsdysphorie.

Beyond NICE: Updated Systematic Review on the Current Evidence of Using Puberty Blocking Pharmacological Agents and Cross-Sex-Hormones in Minors with Gender Dysphoria Abstract: Objective: The suppression of physiological puberty using puberty-blocking pharmacological agents (PB) and prescribing cross-sex hormones (CSH) to minors with gender dysphoria (GD) is a current matter of discussion, and in some cases, PB and CSH are used in clinical practice for this particular population. Two systematic reviews (one on PB, one on CSH treatment) by the British National Institute for Clinical Excellence (NICE) from 2020 indicated no clear clinical benefit of such treatments regarding critical outcome variables. In particular, these two systematic NICE reviews on the use of PB and CSH in minors with GD detected no clear improvements of GD symptoms. Moreover, the overall scientific quality of the available evidence, as discussed within the above-mentioned two NICE reviews, was classified as "very low certainty" regarding modified GRADE criteria. Method: The present systematic review presents an updated literature search on this particular topic (use of PB and CSH in minors with GD) following NICE principles and PICO criteria for all relevant new original research studies published since the release of the two above-mentioned NICE reviews (updated literature search period was July 2020-August 2023). Results: The newly conducted literature search revealed no newly published original studies targeting NICE-defined critical and important outcomes and the related use of PB in minors with GD following PICO criteria. For CSH treatment, we found two new studies that met PICO criteria, but these particular two studies had low participant numbers, yielded no significant additional clear evidence for specific and clearly beneficial effects of CSH in minors with GD, and could be classified as "low certainty" tfollowing modified GRADE criteria. Conclusions: The currently available studies on the use of PB and CSH in minors with GD have significant conceptual and methodological flaws. The available evidence on the use of PB and CSH in minors with GD is very limited and based on only a few studies with small numbers, and these studies have problematic methodology and quality. There also is a lack of adequate and meaningful long-term studies. Current evidence doesn't suggest that GD symptoms and mental health significantly improve when PB or CSH are used in minors with GD. Psychotherapeutic interventions to address and reduce the experienced burden can become relevant in children and adolescents with GD. If the decision to use PB and/or CSH is made on an individual case-by-case basis and after a complete and thorough mental health assessment, potential treatment of possibly co-occurring mental health problems as well as after a thoroughly conducted and carefully executed individual risk-benefit evaluation, doing so as part of clinical studies or research projects, as currently done in England, can be of value in terms of generation of new research data. The electronic supplement (ESM) 1 is an adapted and abreviated English version of this work.

Pulmonary arterial hypertension: Sex matters.

Pulmonary arterial hypertension (PAH) is a complex disease of multifactorial origin. While registries have demonstrated that women are more susceptible to the disease, females with PAH have superior right ventricle (RV) function and a better prognosis than their male counterparts, a phenomenon referred to as the 'estrogen paradox'. Numerous pre-clinical studies have investigated the involvement of sex hormones in PAH pathobiology, often with conflicting results. However, recent advances suggest that abnormal estrogen synthesis, metabolism and signalling underpin the sexual dimorphism of this disease. Other sex hormones, such as progesterone, testosterone and dehydroepiandrosterone may also play a role. Several non-hormonal factor including sex chromosomes and epigenetics have also been implicated. Though the underlying pathophysiological mechanisms are complex, several compounds that modulate sex hormones levels and signalling are under investigation in PAH patients. Further elucidation of the estrogen paradox will set the stage for the identification of additional therapeutic targets for this disease.

Shuangshi Tonglin Capsule treats benign prostatic hyperplasia through the ROS/NLRP3 signaling pathway.

OBJECTIVE: To explore the effects of the SSTL on BPH and clarify the therapeutic mechanisms. METHODS: Animal model of BPH was established by castration and subcutaneous injection of TP into SD rats; rats were orally administered SSTL for 28 days while modeling. Detection of PI, LI and RI in rats, to observe histopathological changes and collagen deposition in the prostate tissue. Detects levels of sex hormones and inflammatory factors in serum and tissues of rats, the test kit detects levels of lipid peroxides and antioxidants in serum and tissues. Fluorescent staining analysis of tissue ROS; the expression of NLRP3 inflammatory vesicles was observed by immunohistochemistry; Western blotting detected the expression of NOX4, NOX2, NLRP3 inflammatory vesicles, ASC, Cleaved Caspase-1, Caspase-1, IL-1ß. RESULTS: After SSTL capsule treatment, the PI and RI of the rats decrease. HE and Masson staining showed that SSTL ameliorated the pathological damage and reduced collagen deposition in the prostate tissue of BPH rats; ELISA results showed that SSTL was able to reduce T, DHT, TNF-α, IL-1ß levels in BPH rats. The test kit showed that SSTL made the levels of MDA, CAT and GSH-Px in the serum and prostate tissue of rats and increased the activity of SOD. The results of ROS fluorescence showed that the ROS level was reduced in SSTL group; Western blotting showed that SSTL could cause down-regulation of NOX4, NOX2, NLRP3, ASC, Cleaved Caspase-1, IL-1ß protein expression. CONCLUSION: SSTL can reduce the PI and RI in BPH rats, it can also inhibit the level of sex hormones and inflammatory factors in BPH rats, which thereby reducing the histopathological damage of prostate gland in BPH rats, and can treat BPH in rats through ROS/NLRP3 pathway.

Sex hormones, insomnia, and sleep quality: Subjective sleep in the first year of hormone use in transgender persons.

STUDY OBJECTIVES: Transgender persons can use gender-affirming hormone therapy (GAHT) to align their physical appearance with their identified gender. Many transgender persons report poor sleep, but the effects of GAHT on sleep are unknown. This study examined the effects of a 12 months of GAHT use on self-reported sleep quality and insomnia severity. METHODS: A sample of 262 transgender men (assigned female at birth, started masculinizing hormone use) and 183 transgender women (assigned male at birth, started feminizing hormone use), completed self-report questionnaires on insomnia (range 0-28), sleep quality (range 0-21) and sleep onset latency, total sleep time and sleep efficiency before start of GAHT and after 3, 6, 9, and 12 months of GAHT. RESULTS: Reported sleep quality showed no clinically significant changes after GAHT. Insomnia showed significant but small decreases after 3 and 9 months of GAHT in trans men (-1.11; 95%CI: -1.82; -0.40 and -0.97; 95%CI: -1.81; -0.13, respectively) but no changes in trans women. In trans men, reported sleep efficiency decreased by 2.8% (95%CI: -5.5%; -0.2%) after 12 months of GAHT. In trans women, reported sleep onset latency decreased by 9 min (95%CI: -15; -3) after 12 months of GAHT. CONCLUSIONS: These findings show that 12 months of GAHT use did not result in clinically significant changes in insomnia or sleep quality. Reported sleep onset latency and reported sleep efficiency showed small to modest changes after 12 months of GAHT. Further studies should focus on underlying mechanisms by which GAHT could affect sleep quality.

Hormonothérapie injectable et réduction des risques : pratiques, difficultés, santé des personnes trans en France.

INTRODUCTION: Hormone therapy (HT) adherence practices among trans people are poorly studied. For a large proportion of these people, HT is administered parenterally. The unavailability of certain treatments in France, combined with poor institutional care, keeps injectors away from the health care system and encourages potentially risky injection practices. Following a significant increase in the number of trans people in its active list, the association Safe, coordinator of the remote harm reduction system in France, conducted a cross-sectional descriptive study from December 2020 to February 2021 using an anonymous self-administered online questionnaire. PURPOSE OF RESEARCH: The objective is to better understand the profile of trans people who inject their HT and their injection practices. RESULTS: We observed that a significant proportion of trans injectors do not benefit from professional support, either to obtain treatment or to carry out the injection. This situation can lead to certain misuses of medical supplies, such as needle sharing or reuse, which present significant health risks. This is especially true for injectors whose treatment is not legally available and who obtain it through parallel markets. This study also underlines the importance of self-support associations to accompany transition. CONCLUSIONS: We therefore propose that a harm reduction policy adapted to the practices of trans people be implemented in order to better support this population and avoid the emergence of major health problems such as HIV infection.

Sex steroid hormones and epilepsy: Effects of hormonal replacement therapy on seizure frequency of postmenopausal women with epilepsy-A systematic review.

BACKGROUND AND PURPOSE: Hormonal replacement therapy (HRT) is used for symptomatic treatment of menopause. Some evidence suggests a proconvulsant effect of estrogen and an anticonvulsant role of progesterone. Thus, the use of exogenous sex steroid hormones might influence the course of epilepsy in peri- and postmenopausal women with epilepsy (WWE). We conducted a systematic review on the impact of HRT on the frequency of seizures of WWE. METHODS: PubMed and Scopus were searched for articles published from inception until August 2022. Abstracts from the past 5 years from the European Academy of Neurology and European Epilepsy Congresses were also reviewed. Article reference lists were screened, and relevant articles were retrieved for consultation. Interventional and observational studies on WWE and animal models of estrogen deficiency were included. Critical appraisal was performed using the revised Cochrane risk-of-bias tool for randomized trials and ROBINS-E tool. RESULTS: Of 497 articles screened, 13 studies were included, including three human studies. One cross-sectional study showed a decrease in seizure frequency in WWE using combined HRT, a case-control study showed an increase in comparison with controls, and a randomized clinical trial found a dose-dependent increase in seizure frequency in women with focal epilepsy taking combined HRT. Ten studies addressing the impact of HRT in rat models were also included, which showed conflicting results. CONCLUSIONS: There is scarce evidence of the impact of HRT in WWE. Further studies should evaluate the harmful potential, and prospective registries are needed for monitoring this population.

Cancer-biomarkers associated with sex hormone receptors and recent therapeutic advancements: a comprehensive review.

Hormones and its regulation plays vital role in causing breast, prostate, ovarian and endometrial cancers collectively known as hormone-sensitive cancers. This review discusses the various functions of the sex hormones and the biological pathways involved in causing hormone-associated cancer under differential regulation. We have also attempted to explore the biomarkers associated with the cancers and the current therapeutic availability to treat such cancers. Among various sex hormones such as estrogen, progesterone and androgen, estrogen the female sex hormone and its receptor had a major contribution in causing cancer and hence are considered a predominant target in treating the associated cancers. Other hormones and receptors such a androgen, progesterone, and their respective receptors were also reported to have a significant correlation in causing cancers. Apart from these receptors certain enzymes that act as precursors or as promoters are also targeted for treatment strategies. The drugs commonly used belong to the selective drug classes such as selective estrogen receptor modulators and selective progesterone receptor modulators. In the case of androgen regulation androgen deprivation therapies are practiced. It is also suggested that the use of natural substances to treat cancer could prevent resistance and reduce side effects. Identification of significant targets and the discovery of many efficient drugs shall be possible in the future with better understanding of hormone regulation and its influence on cancer causative mechanisms.

Effects of filgotinib on semen parameters and sex hormones in male patients with inflammatory diseases: results from the phase 2, randomised, double-blind, placebo-controlled MANTA and MANTA-RAy studies.

OBJECTIVES: The phase 2 MANTA and MANTA-RAy studies aimed to determine if the oral Janus kinase 1 preferential inhibitor filgotinib affects semen parameters and sex hormones in men with inflammatory diseases. METHODS: MANTA (NCT03201445) and MANTA-RAy (NCT03926195) included men (21-65 years) with active inflammatory bowel disease (IBD) and rheumatic diseases (rheumatoid arthritis, spondyloarthritis or psoriatic arthritis), respectively. Eligible participants had semen parameters in the normal range per the WHO definition. In each study, participants were randomised 1:1 to receive once-daily, double-blind filgotinib 200 mg or placebo for 13 weeks for pooled analysis of the primary endpoint (proportion of participants with a ≥50% decrease from baseline in sperm concentration at week 13). Participants who met the primary endpoint were monitored over an additional 52 weeks for 'reversibility'. Secondary endpoints included change from baseline to week 13 in: sperm concentration, total motility, normal morphology, total count and ejaculate volume. Sex hormones (luteinising hormone, follicle stimulating hormone, inhibin B and total testosterone) and reversibility were exploratory endpoints. RESULTS: Across both studies, 631 patients were screened, and 248 were randomised to filgotinib 200 mg or placebo. Baseline demographics and characteristics were similar within indications between treatment groups. Numerically similar proportions of filgotinib-treated versus placebo-treated patients met the primary endpoint (8/120 (6.7%) vs 10/120 (8.3%)), Δ-1.7% (95% CI -9.3% to 5.8%)). There were no clinically relevant changes from baseline to week 13 in semen parameters or sex hormones, or patterns of reversibility between treatment groups. Filgotinib was well tolerated, with no new safety events. CONCLUSIONS: Results suggest that once daily filgotinib 200 mg for 13 weeks has no measurable impact on semen parameters or sex hormones in men with active IBD or inflammatory rheumatic diseases.

GENDER-RELATED VARIATIONS IN PATHOPHYSIOLOGICAL RESPONSES TO METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS PNEUMONIA AND SEPSIS.

ABSTRACT: In preclinical studies, the protective effects of female sex hormones and the immunosuppressive effects of male sex hormones were demonstrated. However, gender-related differences in multiorgan failure and mortality in clinical trials have not been consistently explained. This study aims to investigate gender-related differences in the development and progression of sepsis using a clinically relevant ovine model of sepsis. Adult Merino male (n=7) and female (n=7) sheep were surgically prepared with multiple catheters before the study. To induce sepsis, bronchoscopy instilled methicillin-resistant Staphylococcus aureus into sheep's lungs. The time from the bacterial inoculation until the modified Quick Sequential Organ Failure Assessment (q-SOFA) score became positive was measured and analyzed primarily. We also compared the SOFA score between these male and female sheep over time. Survival, hemodynamic changes, the severity of pulmonary dysfunction, and microvascular hyperpermeability were also compared. The time from the onset of bacterial inoculation to the positive q-SOFA in male sheep was significantly shorter than in female sheep. Mortality was not different between these sheep (14% vs. 14%). There were no significant differences in hemodynamic changes and pulmonary function between the two groups at any time point. Similar changes in hematocrit, urine output, and fluid balance were observed between females and males. The present data indicate that the onset of multiple organ failure and progression of sepsis is faster in male sheep than in female sheep, even though the severity of cardiopulmonary function is comparable over time. Further studies are warranted to validate the above results.

Increasing incidence rate of breast cancer in cystic fibrosis - relationship between pathogenesis, oncogenesis and prediction of the treatment effect in the context of worse clinical outcome and prognosis of cystic fibrosis due to estrogens.

Cystic fibrosis (CF) is the most common genetic disease in the Caucasion population. Thanks to the CFTR modulators therapy, life expectancy will significantly improve. New therapeutic challenges can be expected, including diseases associated with ageing and higher incidence of cancer, as evidenced by recent epidemiological studies. The increasing incidence of tumors includes also breast cancer. The risk of breast cancer is higher in CF patients compared to the general population. Sex hormones, especially estrogens, also affect on the pathophysiology and immunology of the CF. Previous research, has demonstrated unequivocal survival rates for female CF patients compared to their male counterparts. Is demonstrated, that chemotherapy used for breast cancer affects the CFTR channel and CFTR modulator therapy has frequent side effects on breast tissue. In this review, we focus on the effects of female sex hormones on CF disease, pathophysiological relationships between CF and breast cancer, and the impact of antitumor treatment on both, malignant disease and CF. The potential for further investigation is also discussed.

Psychosocial Functioning in Transgender Youth after 2 Years of Hormones.

BACKGROUND: Limited prospective outcome data exist regarding transgender and nonbinary youth receiving gender-affirming hormones (GAH; testosterone or estradiol). METHODS: We characterized the longitudinal course of psychosocial functioning during the 2 years after GAH initiation in a prospective cohort of transgender and nonbinary youth in the United States. Participants were enrolled in a four-site prospective, observational study of physical and psychosocial outcomes. Participants completed the Transgender Congruence Scale, the Beck Depression Inventory-II, the Revised Children's Manifest Anxiety Scale (Second Edition), and the Positive Affect and Life Satisfaction measures from the NIH (National Institutes of Health) Toolbox Emotion Battery at baseline and at 6, 12, 18, and 24 months after GAH initiation. We used latent growth curve modeling to examine individual trajectories of appearance congruence, depression, anxiety, positive affect, and life satisfaction over a period of 2 years. We also examined how initial levels of and rates of change in appearance congruence correlated with those of each psychosocial outcome. RESULTS: A total of 315 transgender and nonbinary participants 12 to 20 years of age (mean [±SD], 16±1.9) were enrolled in the study. A total of 190 participants (60.3%) were transmasculine (i.e., persons designated female at birth who identify along the masculine spectrum), 185 (58.7%) were non-Latinx or non-Latine White, and 25 (7.9%) had received previous pubertal suppression treatment. During the study period, appearance congruence, positive affect, and life satisfaction increased, and depression and anxiety symptoms decreased. Increases in appearance congruence were associated with concurrent increases in positive affect and life satisfaction and decreases in depression and anxiety symptoms. The most common adverse event was suicidal ideation (in 11 participants [3.5%]); death by suicide occurred in 2 participants. CONCLUSIONS: In this 2-year study involving transgender and nonbinary youth, GAH improved appearance congruence and psychosocial functioning. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development.).

Effect of Mirena intrauterine device combined with GNRH-A on endometriosis, sex hormone level and carbohydrate antigen 125.

To investigate the clinical value of Mirena (levonorgestrel intrauterine sustained release system) combined with gonadotropin-releasing hormone agonist (GnRH-a) in patients with endometriosis, 80 patients with endometriosis (March 2019 ~ March 2020) were selected as the research object. According to the "random number table method", they were divided into the control group (treated with GnRH-a) and the observation group (treated with Mirena IUD combined with GnRH-a), with 40 cases included in each group. The total clinical efficacy, sex hormone level, carbohydrate antigen 125 (CA125) level, degree of pain and recurrence rate indexes were compared between the two groups. Results showed that the total effective rate of 92.50% in the observation group was higher than 75.00% in the control group (P < 0.05). Intercourse pain of dysmenorrhea and sexual intercourse pain (VAS) in the two groups were compared before treatment. After treatment, the VAS scores in the two groups decreased, and the VAS scores in the observation group were lower than those in the control group (P<0.05). The levels of E2, FSH, LH and CA125 in the observation group were lower than in the control group (P<0.05). The recurrence rate of 5.00% in the observation group was lower than 20.00% in the control group (P<0.05). In conclusion, Mirena IUD combined with GnRH-a can improve the clinical efficacy of endometriosis, improve ovarian function, effectively regulate serum factors, further alleviate the symptoms of sexual intercourse pain and dysmenorrhea, control the risk of postoperative recurrence and achieve an ideal therapeutic effect.

Clinical Follow-up of Two Adolescents Diagnosed with Gender Dysphoria. / Cinsiyetinden Hosnutsuzlugu Olan Iki Ergenin Klinik Izlem Süreci.

Rapid physical, psychological and sexual changes in adolescents due to the developmental process differentiate the approach to adolescents with gender dysphoria (GD) from the approach to adults. In this article, two adolescents who applied for GD and followed up for a long time are presented. The first case was assigned male at birth and defined herself as female. At the age of fifteen, a gonadotropin-releasing hormone analog was started for puberty suppression, and sex hormone was started in the follow-up. The second case's assigned sex was female and defined himself as male. At the age of sixteen years and six months, puberty suppressive treatment was started, followed by sex hormones. Both cases were able to continue their psychosocial development without any problems after the psychiatric and physical treatments they could reach on time. Although GD in adolescents cannot be resolved with puberty suppression alone, it creates time to resolve the acute problems and to search for appropriate treatment approaches in the future. Puberty suppression partially relieves and prevents the exacerbation of the dysphoria experienced by the youth diagnosed as GD, and creates time to search appropriate treatment approaches in the follow-up. Through these two cases, it is aimed to introduce the gender affirmation processes of adolescents with GD, to discuss the medical interventions in adolescence and the psychosocial effects of the process on individuals. Keywords: Gender dysphoria, gender incongruence, adolescence, gender affirmation process, puberty supression, puberty blockers.

Obesity-related asthma in children and adolescents.

There is substantial epidemiological and experimental evidence of an obesity-related asthma phenotype. Compared to children of healthy weight, children with obesity are at higher risk of asthma. Children with obesity who have asthma have greater severity and poorer control of their asthma symptoms, more frequent asthma exacerbations, and overall lower asthma-related quality of life than children with asthma who have a healthy weight. In this Review, we examine some of the latest evidence on the characteristics of this phenotype and its main underlying mechanisms, including genetics and genomics, changes in airway mechanics and lung function, sex hormone differences, alterations in immune responses, systemic and airway inflammation, metabolic dysregulation, and modifications in the microbiome. We also review current recommendations for the treatment of these children, including in the management of their asthma, and current evidence for weight loss interventions. We then discuss initial evidence for potential novel therapeutic approaches, such as dietary modifications and supplements, antidiabetic medications, and statins. Finally, we identify knowledge gaps and future directions to improve our understanding of asthma in children with obesity, and to improve outcomes in these susceptible children. We highlight important needs, such as designing paediatric-specific studies, implementing large multicentric trials with standardised interventions and outcomes, and including racial and ethnic groups along with other under-represented populations that are particularly affected by obesity and asthma.

[Adverse effects of opioids, antidepressants and anticonvulsants on sex hormones : Often unnoticed but clinically relevant]. / Unerwünschte Wirkungen von Opioiden, Antidepressiva und Antikonvulsiva auf Sexualhormone : Häufig unbeachtet, aber klinisch relevant.

Androgen insufficiency under treatment with opioids, antidepressants and anticonvulsants in chronic pain diseases is a side effect with a high prevalence. It can lead to clinical metabolic alterations, adynamia, stress intolerance, anemia or osteoporosis and has a significant impact on the quality of life. Opioids, antidepressants and anticonvulsants affect the hypothalamic-pituitary-gonadal axis of sex hormones. A urologist, andrologist or endocrinologist should be involved in the treatment at an early stage. The recommendation of a differential therapeutic selection of certain substances is only indicative and does not meet evidential criteria. The indications for androgen substitution must be individualized and in consideration of the risk-benefit profile. Awareness of this side effect of an otherwise lege artis medicinal pain therapy must be sharpened and compulsory included in the differential diagnostic considerations.

Puberty Blockers for Children: Can They Consent?

Gender dysphoria is a persistent distress about one's assigned gender. Referrals regarding gender dysphoria have recently greatly increased, often of a form that is rapid in onset. The sex ratio has changed, most now being natal females. Mental health issues pre-date the dysphoria in most. Puberty blockers are offered in clinics to help the child avoid puberty. Puberty blockers have known serious side effects, with uncertainty about their long-term use. They do not improve mental health. Without medication, most will desist from the dysphoria in time. Yet over 90% of those treated with puberty blockers progress to cross-sex hormones and often surgery, with irreversible consequences. The brain is biologically and socially immature in childhood and unlikely to understand the long-term consequences of treatment. The prevailing culture to affirm the dysphoria is critically reviewed. It is concluded that children are unable to consent to the use of puberty blockers.

Sex and Gender Considerations in Episodic Migraine.

PURPOSE OF REVIEW: We seek to update readers on recent advances in our understanding of sex and gender in episodic migraine with a two part series. In part 1, we examine migraine epidemiology in the context of sex and gender, differences in symptomatology, and the influence of sex hormones on migraine pathophysiology (including CGRP). In part 2, we focus on practical clinical considerations for sex and gender in episodic migraine by addressing menstrual migraine and the controversial topic of hormone-containing therapies. We make note of data applicable to gender minority populations, when available, and summarize knowledge on gender affirming hormone therapy and migraine management in transgender individuals. Finally, we briefly address health disparities, socioeconomic considerations, and research bias. RECENT FINDINGS: Migraine is known to be more prevalent, frequent, and disabling in women. There are also differences in migraine co-morbidities and symptomatology. For instance, women are likely to experience more migraine associated symptoms such as nausea, photophobia, and phonophobia. Migraine pathophysiology is influenced by sex hormones, e.g., estrogen withdrawal as a known trigger for migraine. Other hormones such as progesterone and testosterone are less well studied. Relationships between CGRP (the target of new acute and preventive migraine treatments) and sex hormones have been established with both animal and human model studies. The natural course of migraine throughout the lifetime suggests a contribution from hormonal changes, from puberty to pregnancy to menopause/post-menopause. Treatment of menstrual migraine and the use of hormone-containing therapies remains controversial. Re-evaluation of the data reveals that stroke risk is an estrogen dose- and aura frequency-dependent phenomenon. There are limited data on episodic migraine in gender minorities. Gender affirming hormone therapy may be associated with a change in migraine and unique risks (including ischemic stroke with high dose estrogen). There are key differences in migraine epidemiology and symptomatology, thought to be driven at least in part by sex hormones which influence migraine pathophysiology and the natural course of migraine throughout the lifetime. More effective and specific treatments for menstrual migraine are needed. A careful examination of the data on estrogen and stroke risk suggests a nuanced approach to the issue of estrogen-containing contraception and hormone replacement therapy is warranted. Our understanding of sex and gender is evolving, with limited but growing research on the relationship between gender affirming therapy and migraine, and treatment considerations for transgender people with migraine.

Women With Turner Syndrome Are Both Estrogen and Androgen Deficient: The Impact of Hormone Replacement Therapy.

CONTEXT: Women with Turner syndrome (TS) suffer from hypergonadotropic hypogonadism, causing a deficit in gonadal hormone secretion. As a consequence, these women are treated with estrogen from the age of 12 years, and later in combination with progesterone. However, androgens have been given less attention. OBJECTIVE: To assess sex hormone levels in women with TS, both those treated and those nontreated with hormone replacement therapy (HRT), and investigate the impact of HRT on sex hormone levels. METHODS: At Aarhus University Hospital, 99 women with TS were followed 3 times from August 2003 to February 2010. Seventeen were lost during follow-up. Control group 1 consisted of 68 healthy age-matched control women seen once during this period. Control group 2 consisted of 28 young, eumenorrheic women sampled 9 times throughout the same menstrual cycle. Serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), 17ß-estradiol, estrone sulfate, DHEAS, testosterone, free androgen index, androstenedione, 17-OH progesterone, and sex hormone-binding globulin (SHBG) were analyzed. RESULTS: All androgens, 17-OH progesterone, and sex hormone-binding globulin (SHBG) were 30% to 50% lower in TS compared with controls (P < 0.01). FSH, LH, and estrone sulfate were more than doubled in women with TS compared with controls (P < 0.02). Using principal component analysis, we describe a positive correlation between women with TS receiving HRT, elevated levels of SHBG, and decreased levels of androgens. CONCLUSION: The sex hormone profile in TS reveals a picture of androgen deficiency, aggravated further by HRT. Conventional HRT does not normalize estradiol levels in TS.