Ovarian 17α-hydroxyprogesterone responses to GnRH analog testing in oligomenorrheic insulin-dependent diabetic adolescents

Virdis, R; Zampolli, Maria; Street, Maria Elisabeth; Vanelli, Maurizio; Potau, Neus; Terzi, Cesare; Ghizzoni, Lucia; Ibáñez, Lourdes

doi:10.1530/eje.0.1360624

Cited by 20 publications

(10 citation statements)

References 21 publications

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“…This was also supported by the finding of androgenized ovarian responses to the gonadotropinreleasing hormone analog leuprolide in these women, consisting of increased circulating 17-hydroxyprogesterone concentrations (24,25). However, as happens in women without diabetes, the adrenal glands may also contribute to androgen excess in women with PCOS and type 1 diabetes, explaining the mildly increased dehydroepiandrosterone sulfate levels found in some series (14,28).…”

Section: Systematic Reviewsupporting

confidence: 54%

“…Six addressed fertility issues and eighteen addressed menstrual cycle characteristics of type 1 diabetes but were unrelated to androgen excess ( Fig. 1 and Supplementary Data), leaving seventeen original articles dealing with androgen excess (8)(9)(10)(11)(12)(13)(14)(15)(16)(24)(25)(26)(27)(28)(29)(30)(31). Only 9 of these 17 articles contained data about the prevalence of PCOS and related traits (8,(10)(11)(12)(13)(14)(15)(16)28) and were included in the meta-analyses.…”

Section: Data Synthesis and Analysismentioning

confidence: 99%

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Type 1 Diabetes and Polycystic Ovary Syndrome: Systematic Review and Meta-analysis

Escobar-Morreale

Roldán-Martín

2016

Diabetes Care

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A few small studies have reported increased prevalences of polycystic ovary syndrome (PCOS) and symptoms of androgen excess in women with type 1 diabetes. PURPOSEWe performed a systematic review and meta-analysis of studies evaluating androgen excess symptoms and PCOS in women with type 1 diabetes. DATA SOURCESThe Entrez-PubMed and Scopus electronic databases were used. STUDY SELECTIONWe selected studies addressing androgen excess signs, symptoms, and disorders in girls, adolescents, and adult women with type 1 diabetes. DATA EXTRACTIONThe main outcome measures were prevalences of PCOS, hyperandrogenemia, hirsutism, menstrual dysfunction, and polycystic ovarian morphology (PCOM). DATA SYNTHESISNine primary studies involving 475 adolescent or adult women with type 1 diabetes were included. The prevalences of PCOS and associated traits in women with type 1 diabetes were 24% (95% CI 15-34) for PCOS, 25% (95% CI 17-33) for hyperandrogenemia, 25% (95% CI 16-36) for hirsutism, 24% (95% CI 17-32) for menstrual dysfunction, and 33% (95% CI 24-44) for PCOM. These figures are considerably higher than those reported earlier in the general population without diabetes. LIMITATIONSThe data collected in the original studies were heterogeneous in age, race, ethnicity, and criteria used for the diagnosis of PCOS; yet, we used a quality-effects model in the meta-analyses to overcome this limitation. CONCLUSIONSPCOS and its related traits are frequent findings in women with type 1 diabetes. PCOS may contribute to the subfertility of these women by a mechanism that does not directly depend on glycemic/metabolic control among other negative consequences for their health. Hence, screening for PCOS and androgen excess should be included in current guidelines for the management of type 1 diabetes in women.

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Section: Systematic Reviewsupporting

confidence: 54%

Section: Data Synthesis and Analysismentioning

confidence: 99%

Type 1 Diabetes and Polycystic Ovary Syndrome: Systematic Review and Meta-analysis

Escobar-Morreale

Roldán-Martín

2016

Diabetes Care

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“…Virdis et al (33) found functional ovarian hyperandrogenism, defined by an exaggerated serum 17-OHP response to the GnRH analog leuprolide, in five of nine women with type 1 diabetes mellitus and oligomenorrhea, supporting a role for the ovary as the source of androgen excess in type 1 diabetic women.…”

Section: Discussionmentioning

confidence: 97%

High Prevalence of the Polycystic Ovary Syndrome and Hirsutism in Women with Type 1 Diabetes Mellitus1

Escobar‐Morreale¹,

Roldán

Barrio

et al. 2000

The Journal of Clinical Endocrinology &Amp; Metabolism

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The current recommendation for strict metabolic control of type 1 diabetes mellitus requires the administration of supraphysiological doses of insulin, which might result in insulin-mediated stimulation of androgen synthesis, as occurs in insulin-resistant states. At present, the prevalence of hyperandrogenic disorders in women with type 1 diabetes mellitus is unknown.Eighty-five women with type 1 diabetes mellitus were evaluated for symptoms and signs of hyperandrogenism. In 68 of the patients, several serum androgen and hormone concentrations were measured. The polycystic ovary syndrome (PCOS) was defined by the presence of menstrual dysfunction, together with clinical and/or biochemical evidence of hyperandrogenism, and exclusion of other etiologies. Eighteen healthy women, menstruating regularly, served as controls for the androgenic profiles.Thirty-three patients (38.8%) presented hyperandrogenic disorders (16 had PCOS, and 17 had hirsutism without menstrual dysfunction). Type 1 diabetic patients with PCOS presented increased serum total and free testosterone concentrations, and serum androstenedione levels, but had normal serum sex hormone-binding globulin and dehydroepiandrosterone-sulfate levels. Hirsute type 1 diabetic women without menstrual dysfunction presented normal serum androgen levels. There were no significant differences between hyperandrogenic and nonhyperandrogenic type 1 diabetes mellitus women in clinical variables such as the duration of diabetes, age at diagnosis of diabetes, conventional or intensive insulin therapy, mean daily insulin dosage, or metabolic control.In conclusion, women with type 1 diabetes mellitus have a high prevalence of hyperandrogenic disorders, including PCOS and hirsutism. (J Clin Endocrinol Metab 85: 4182-4187, 2000)

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“…Alteração menstrual é comum em pacientes com diabetes tipo 1, estando presente em aproximadamente 20% das pacientes (15)(16)(17)(18)(19)(20), incidência essa maior que a observada em mulheres normais, de 8% (21). Inicialmente tal anormalidade foi atribuída ao mau controle do diabetes (17), mas posteriormente se demonstrou que sua presença não decorria do grau de controle (19).…”

Section: Discussionunclassified

“…Inicialmente tal anormalidade foi atribuída ao mau controle do diabetes (17), mas posteriormente se demonstrou que sua presença não decorria do grau de controle (19). Posteriormente, foram demonstradas anormalidades do eixo gonadotrófico em pacientes com diabetes tipo 1 e distúrbio menstrual quando comparadas a pacientes sem distúrbio menstrual (20). Essa maior prevalência de distúrbio menstrual se acompanha também de uma maior incidência de hiperandrogenismo, encontrado em aproximadamente 40% das pacientes, representado principalmente pelo hirsutismo (16,22), porém com um grau menor quando comparado a mulheres hiperan drogênicas não diabéticas.…”

Section: Discussionunclassified

Testosterona falsamente elevada em uma paciente diabética tipo 1 com acne e insuficiência renal crônica em diálise

Marcondes

Martins

Amaral

et al. 2012

Arq Bras Endocrinol Metab

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SUMÁRIODescrevemos uma paciente com diabetes tipo 1 com acne e insuficiência renal crônica, em diálise, que apresentou uma dosagem de testosterona total e livre elevada (612 ng/dL, normal < 90 ng/dL e 255 pMol/L, normal: 20-45 pMol/L, respectivamente). Na avaliação clínica, além da acne facial não havia qualquer outro sinal de hiperandrogenismo. Após ter esse resultado confirmado, ela foi submetida à avaliação morfológica de adrenal e ovários (tomografia computadorizada de adrenal e ultrassom pélvico), cujos resultados foram normais. Na ausência de quadro clínico de virilização, foram consideradas outras possibilidades que pudessem explicar a elevação da testosterona, entre as quais a presença de comorbidades (diabetes e insuficiência renal crônica) e falha do método de dosagem. Uma nova determinação da testosterona total, por meio da cromatografia líquida de alta performance como método preparativo e espectrometria de massa em tandem, resultou normal (21 ng/dL), compatível com uma concentração de testosterona total falsamente elevada pela presença de interferentes com o método de dosagem. Arq Bras Endocrinol Metab. 2012;56(5):319-23 SUMMARYThe purpose of this report is to present the case of a patient with type 1 diabetes with acne and chronic renal failure on dialysis admitted to the hospital with high total total and free testosterone (612 ng/dL, normal < 90 ng/dL; 255 pMol/L, normal: 20-45 pMol/L). On clinical evalua tion, she presented facial acne, and no other signs of hyperandrogenism. As this result was confirmed, she underwent adrenal and ovary morphological assessment (adrenal CT and pelvic ultrasound), which yielded normal results. Due to divergence between clinical and laboratory findings, we considered other possibilities that could explain the elevation of testosterone, including the presence of comorbidities (diabetes and chronic renal failure) and failure of the testosterone assay. Testosterone levels were determined again by high performance liquid chromatography, as a preparative method, and tandem mass spectrometry, yielding normal results (21 ng/dL), which were compatible with a falsely elevated total testosterone level caused by the presence of factors that intereferred with the assay. INTRODUÇÃO A s síndromes hiperandrogênicas englobam doenças que se manifestam pelo aumento da atividade biológica dos andrógenos. Na mulher, essas manifestações incluem hirsutismo, acne, alopecia tipo androgêni-ca, disfunção menstrual, infertilidade, abortamento precoce e sinais de virilização (atrofia do parênquima mamário, alteração da tonalidade da voz, redistribuição de massas musculares e clitoromegalia).Tanto a testosterona total (forma livre e forma ligada às proteínas transportadoras) quanto a testosterona livre são consideradas marcadores sensíveis para a demonstração da hiperandrogenemia (1). Entretanto, não existe correlação entre a concentração dos andrógenos

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Ovarian 17α-hydroxyprogesterone responses to GnRH analog testing in oligomenorrheic insulin-dependent diabetic adolescents

Abstract: About 50% of the oligomenorrheic IDDM adolescents had an increased ovarian 17-OHP response to GnRH analog stimulation in the range of functional ovarian hyperandrogenism. Factors other than metabolic control, such as stress, may play an etiologic role in IDDM ovarian dysfunction.

Cited by 20 publications

References 21 publications

Type 1 Diabetes and Polycystic Ovary Syndrome: Systematic Review and Meta-analysis

Type 1 Diabetes and Polycystic Ovary Syndrome: Systematic Review and Meta-analysis

High Prevalence of the Polycystic Ovary Syndrome and Hirsutism in Women with Type 1 Diabetes Mellitus1

Testosterona falsamente elevada em uma paciente diabética tipo 1 com acne e insuficiência renal crônica em diálise

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