Andrea Prestes Nácul

Key points • Nonclassic congenital adrenal hyperplasia (NCAH) or late onset CAH is a genetic disease with late manifestations in women, usually in late childhood, adolescence or early adulthood. • It is an important differential diagnosis of polycystic ovary syndrome. • More than 90% of the time it is due to a deficiency of the 21-hydroxylase enzyme. Other less frequent causes are mutations in genes affecting the 11-beta-hydroxylase or 3-beta-hydroxysteroid dehydrogenase enzymes. • Its diagnosis is particularly important in women who desire pregnancy. • Treatment among women with hyperandrogenism without reproductive desire can be directed toward controlling clinical manifestations. Recommendations • We recommend screening for NCAH due to 21-hydroxylase (CYP21A2) deficiency in adolescents and adult women who present signs and symptoms of hyperandrogenism (Level of Evidence A). • The diagnosis of NCAH is excluded by measuring baseline 17-OHP < 2 ng/mL ( 10 ng/mL (1,000 ng/dL) and, more frequently > 15 ng/mL (1,500 ng/ dL), the diagnosis of NCAH is established (Level of Evidence A). • When possible, we recommend CYP21A2 genotyping in women presenting 17-OHP values > 10 ng/mL (1,000 ng/dL) with the aim to confirm the diagnosis and for pre-conception counseling (Level of Evidence B). • We recommend the use of oral contraceptives (OC) associated or not with antiandrogens as the first option for treating androgenic manifestations and regularizing menstrual cycles in women who do not wish to become pregnant (Level of Evidence A). • We recommend the use of glucocorticoids in cases where conventional treatment for hirsutism is ineffective or poorly tolerated or when the post-ACTH stimulus cortisol response is less than 18 mcg/dL (Level of Evidence C). • We recommend the use of glucocorticoids that do not cross the placental barrier, such as hydrocortisone, prednisolone or prednisone for patients unable to become pregnant spontaneously or with ovulatory dysfunction and who are not at risk of affected fetuses (Level of Evidence B). • In this situation, glucocorticoid treatment must be continued during pregnancy to avoid miscarriages (Level of Evidence C). • We recommend combining ovulation inducers such as clomiphene citrate, letrozole (off-label) or gonadotropins if glucocorticoids are not sufficient to restore ovulation (Level of Evidence B). • Genetic counseling for the couple is indicated to evaluate genotyping of the partner of women with the nonclassic form to detect a serious mutation (Level of Evidence C). • We recommend referring pregnant women at risk of having female fetuses with genital defects to specialized tertiary and quaternary care centers (Level of Evidence D).

Key points • Hyperprolactinemia (HPRL) is a cause of menstrual irregularity, galactorrhea, hypogonadism and infertility. Recognizing the cause of HPRL is essential to institute appropriate treatment. • Drug treatment with dopamine agonist (DA) is the first line of therapy for symptomatic HPRL due to prolactinoma or idiopathic HPRL. • Dopamine agonist treatment is effective in 80-90% of cases. • Infertility treatment in patients with HPRL is also carried out with DA, aiming to normalize prolactin (PRL) levels. • The risk of symptomatic growth of prolactinomas during pregnancy is related to the size of the tumor, length of previous treatment and higher PRL levels, and is less than 5% in microprolactinomas. • Hyperprolactinemia remission can occur after pregnancy and menopause, and in around 30% of cases following drug treatment. • The use of drugs such as antidepressants and antipsychotics is a frequent cause of HPRL, and has particularities in its management.

Keypoints • Hyperprolactinemia (HPRL) is a cause of menstrual irregularity, galactorrhea, hypogonadism and infertility. • Serum prolactin measurement should only be performed in the presence of compatible symptoms and/or in the presence of a pituitary tumor, even with an incidental diagnosis. Dosage is not recommended as a routine examination. • There are several causes of HPRL. In most cases, it is caused by pregnancy, hypothalamic-pituitary disconnection or PRL-secreting pituitary adenomas (prolactinomas), or it can also be secondary to the use of medications. • Recognizing clinical, laboratory and imaging findings is essential for the diagnosis of prolactinoma, and its differential diagnoses.

Hyperprolactinemia is a frequent cause of menstrual irregularity, galactorrhea, hypogonadism, and infertility. The most common etiologies of hyperprolactinemia can be classified as physiological, pharmacological, and pathological. Among pathological conditions, it is essential to distinguish prolactinomas from other tumors and pituitary lesions presenting with hyperprolactinemia due to pituitary stalk disconnection. Proper investigation considering clinical data, laboratory tests, and, if necessary, imaging evaluation, is important to identify the correct cause of hyperprolactinemia and manage the patient properly. This position statement by [...] ABSTRACT Hyperprolactinemia is a frequent cause of menstrual irregularity, galactorrhea, hypogonadism, and infertility. The most common etiologies of hyperprolactinemia can be classified as physiological, pharmacological, and pathological. Among pathological conditions, it is essential to distinguish prolactinomas from other tumors and pituitary lesions presenting with hyperprolactinemia due to pituitary stalk disconnection. Proper investigation considering clinical data, laboratory tests, and, if necessary, imaging evaluation, is important to identify the correct cause of hyperprolactinemia and manage the patient properly. This position statement by

Dopamine agonists are the first line of treatment for patients with symptomatic hyperprolactinemia due to prolactinomas and in those with idiopathic hyperprolactinemia. Treatment with these agents is effective in 80%-90% of the cases. Infertility treatment of patients with hyperprolactinemia is also carried out with dopamine agonists, aiming for the normalization of prolactin levels. The risk of symptomatic growth of prolactinomas during pregnancy is dependent on the tumor’s size, duration of previous treatments, and prolactin levels. Notably, the corresponding risk [...] ABSTRACT Dopamine agonists are the first line of treatment for patients with symptomatic hyperprolactinemia due to prolactinomas and in those with idiopathic hyperprolactinemia. Treatment with these agents is effective in 80%-90% of the cases. Infertility treatment of patients with hyperprolactinemia is also carried out with dopamine agonists, aiming for the normalization of prolactin levels. The risk of symptomatic growth of prolactinomas during pregnancy is dependent on the tumor’s size, duration of previous treatments, and prolactin levels. Notably, the corresponding risk

The National Specialty Commission on Gynecology Endocrinology of the Brazilian Federation of Gynecology and Obstetrics Associations (FEBRASGO) endorses to this document. The content production is based on scientific studies on a thematic proposal and the findings presented contribute to clinical practice. Article published online: 29 January 2022 © 2022. Federação Brasileira de Ginecologia e Obstetrícia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/) Thieme Revinter Publicações Ltda. Rua do Matoso 170, Rio de Janeiro, RJ, CEP 20270-135, Brazil

The National Specialty Commission on Gynecology Endocrinology of the Brazilian Federation of Gynecology and Obstetrics Associations (FEBRASGO) endorses to this document. The content production is based on scientific studies on a thematic proposal and the findings presented contribute to clinical practice. Article published online: 21 December 2021 © 2021. Federação Brasileira de Ginecologia e Obstetrícia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/) Thieme Revinter Publicações Ltda. Rua do Matoso 170, Rio de Janeiro, RJ, CEP 20270-135, Brazil

Thyroid diseases are relatively common in women in the reproductive period. It is currently understood that clinically-evident thyroid disorders may impair ovulation and, consequently, fertility. However, to date it has not been proven that high serum levels of thyroid-stimulating hormone and/or positivity for antithyroid antibodies are associated to a reduction in fertility, mainly in the absence of altered thyroxine levels. The present comprehensive review aims to present current data on the association between subclinical hypothyroidism and/or thyroid autoimmunity and reproductive outcomes.

The National Specialty Commission for Gynecological Endocrinology of the Brazilian Federation of Gynecology and Obstetrics Associations (FEBRASGO) endorses to this document. The content production is based on scientific studies on a thematic proposal and the findings presented contribute to clinical practice. Article published online: 08 September 2020 © 2020. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/). Thieme Revinter Publicações Ltda Rio de Janeiro, Brazil