Early-Onset Complete Ovarian Failure and Lack of Puberty in a Woman With Mutated Estrogen Receptor ß (ESR2).

Context: Estrogen resistance due to mutations in the estrogen receptor α gene (ESR1) has been described in men and women and is characterized by osteoporosis, delayed bone age and continuous growth in adulthood, and delayed puberty and multiple ovarian cysts in women. Although mutations in the estrogen receptor ß gene ESR2 were found in 46, XY patients with differences of sex development, no genetic variants of ESR2 were linked to gonadal defects in women. Settings and Patient: Here we describe a 16-year-old female patient who came to our tertiary care hospital with complete lack of estrogen action, as demonstrated by absent breast development, primary amenorrhea, and osteoporosis, resembling patients with ESR1 mutation. However, her gonads were clearly abnormal (streak), a finding not observed in ESR1-deficient patients. Design: To gain insights into the molecular consequences of the ESR2 defect, whole exome sequencing and extensive functional transactivation studies in ovarian, bone, and breast cells were conducted, with or without the natural activator of estrogen receptors, 17ß-estradiol. Results: We identified a loss-of-function heterozygous mutation of a highly conserved residue in ESR2 that disrupts estradiol-dependent signaling and has a dominant negative effect, most likely due to failure to interact with its coactivator, nuclear coactivator 1. Conclusions: This is a report of a loss-of-function mutation in the estrogen receptor ß in a young woman with complete ovarian failure, suggesting that ESR2 is necessary for human ovarian determination and/or maintenance and that ESR1 is not sufficient to sustain ovarian function in humans.

[Adolescent gynecology in the medical office]. / Adoleszentengynäkologie in der Praxis.

In the age group of adolescents occur some gynecological problems which present different than in adult women. One is heavy menstrual bleeding, another menstrual problem is life burdening dysmenorrhea. Girls often do not speak about, they do not know what is really normal. Malignant breast masses are very rare, mostly fibroadenoma or cysts are found. With childhood obesity PCOS is a rising hormonal disturbance with impact on future fertility. Counseling adolescents in contraception is another challenge, focused on adherence, chronic disease and disabled teenagers. Together with the risks of unintended pregnancy adolescents have a high risk of sexually transmitted infections. Recommending preservative use and HPV and Hepatitis B vaccination is very important. Cervical cancer screening should start at age 21, girls with special risks (immunodeficiency, very early sexual activity) starting individually at earlier age.

Dans l'adolescence il y a plusieurs problèmes gynécologiques, qui se présentent différentes que chez les femmes adultes. Ce sont plutôt les saignements menstruels forts et la dysménorrhée influente le quotidien. Les jeunes filles n'en parlent pas d'elles mêmes, ne savent pas encore ce qui est normal. Les tumeurs malignes du sein sont rares, il s'agit surtout des fibroadénomes ou des kystes. Avec la progression de l'obésité dans l'enfance le risque pour le syndrome des ovaries polykystique augmente. Celui-ci peut influencer la fertilité. Le conseil de la contraception chez les adolescentes est un défi: Il est très important de prendre en considération les adolescentes avec les maladies chroniques et handicaps. A part des grossesses non désirées les jeunes filles ont un risque plus grand de contracter des infections sexuellement transmissibles. Il faut les encourager à l'utilisation du préservatif e a faire les vaccins de HPV et hépatite B. Le premier prélèvement de cancer commence a l'âge de 21 ans. Les jeunes filles avec des risques particuliers (activité sexuelle précoce, immunodéficience) ont besoin d'un screening avancé individuel.

Nonpuerperal mastitis in adolescents.

Mastitis in non-lactating adolescents is rare and its cause unclear. This retrospective study summarizes 22 such episodes, in 3 of which Staphylococcus aureus was isolated. Serum prolactin levels were normal. Most patients were successfully treated with oral amoxicillin-clavulanic acid. Three patients with bilateral breast cysts had a recurrence.