The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions

Endometriosis is a common condition associated with debilitating pelvic pain and infertility. A genome-wide association study meta-analysis, including 60,674 cases and 701,926 controls of European and East Asian descent, identified 42 genome-wide significant loci comprising 49 distinct association signals. Effect sizes were largest for stage 3/4 disease, driven by ovarian endometriosis. Identified signals explained up to 5.01% of disease variance and regulated expression or methylation of genes in endometrium and blood, many of which were associated with pain perception/maintenance (SRP14/BMF, GDAP1, MLLT10, BSN and NGF). We observed significant genetic correlations between endometriosis and 11 pain conditions, including migraine, back and multisite chronic pain (MCP), as well as inflammatory conditions, including asthma and osteoarthritis. Multitrait genetic analyses identified substantial sharing of variants associated with endometriosis and MCP/migraine. Targeted investigations of genetically regulated mechanisms shared between endometriosis and other pain conditions are needed to aid the development of new treatments and facilitate early symptomatic intervention

The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions

Endometriosis is a common condition associated with debilitating pelvic pain and infertility. A genome-wide association study meta-analysis, including 60,674 cases and 701,926 controls of European and East Asian descent, identified 42 genome-wide significant loci comprising 49 distinct association signals. Effect sizes were largest for stage 3/4 disease, driven by ovarian endometriosis. Identified signals explained up to 5.01% of disease variance and regulated expression or methylation of genes in endometrium and blood, many of which were associated with pain perception/maintenance (SRP14/BMF, GDAP1, MLLT10, BSN and NGF). We observed significant genetic correlations between endometriosis and 11 pain conditions, including migraine, back and multisite chronic pain (MCP), as well as inflammatory conditions, including asthma and osteoarthritis. Multitrait genetic analyses identified substantial sharing of variants associated with endometriosis and MCP/migraine. Targeted investigations of genetically regulated mechanisms shared between endometriosis and other pain conditions are needed to aid the development of new treatments and facilitate early symptomatic intervention

Sexual Orientation and Age at Menarche in Three U.S. Longitudinal Cohorts

PURPOSE: The aim of this study is to examine age at menarche across sexual orientation groups. METHODS: Data were obtained from 131,090 female participants, born 1947-2001, in 3 longitudinal studies-the Growing Up Today Study and Nurses\u27 Health Study 2 and 3. We estimated the association between sexual orientation and age at menarche using regression models adjusted for age, race/ethnicity, birthweight, height, and body mass index. RESULTS: Compared to heterosexual participants, sexual minorities were younger at menarche. Sexual minorities were more likely to have early menarche (≤11 years) and less likely to have late menarche (≥14 years) compared to heterosexual girls. As an example of this pattern, Nurses\u27 Health Study 3 bisexual participants were \u3e30% more likely than heterosexuals to have early versus average menarche (odds ratio 1.37, 95% confidence interval 1.09-1.72). CONCLUSION: Sexual minority girls have a younger age at menarche than heterosexual girls and may benefit from screening for adverse outcomes associated with early menarche

Magnetic resonance imaging and spectroscopy evidence of efficacy for adrenal and gonadal hormone replacement therapy in anorexia nervosa.

PURPOSE: Dehydroepiandrosterone (DHEA)+estrogen/progestin therapy for adolescent girls with anorexia nervosa (AN) has the potential to arrest bone loss. The primary aim of this study was to test the effects of DHEA+estrogen/progestin therapy in adolescent girls with AN on bone marrow in the distal femur using magnetic resonance imaging (MRI) and spectroscopy. METHODS: Seventy adolescent girls with AN were enrolled in a double blind, randomized, placebo-controlled trial at two urban hospital-based programs. INTERVENTION: Seventy-six girls were randomly assigned to receive 12months of either oral micronized DHEA or placebo. DHEA was administered with conjugated equine estrogens (0.3mg daily) for 3months, then an oral contraceptive (20μg ethinyl estradiol/ 0.1mg levonorgestrel) for 9months. The primary outcome measure was bone marrow fat by MRI and magnetic resonance spectroscopy (MRS). RESULTS: T2 of the water resonance dropped significantly less in the active vs. placebo group over 12months at both the medial and lateral distal femur (p=0.02). Body mass index (BMI) was a significant effect modifier for T1 and for T2 of unsaturated (T2 CONCLUSIONS: These findings suggest treatment with oral DHEA+estrogen/progestin arrests the age- and disease-related changes in marrow fat composition in the lateral distal femur reported previously in this population