Gonadotrophin and gonadal steroid response to a single dose of a long‐acting agonist of gonadotrophin‐releasing hormone in ovulatory and anovulatory women with polycystic ovary syndrome

White, Davinia; Leigh, A. J.; Wilson, Catherine; Donaldson, A.; Franks, Stephen

doi:10.1111/j.1365-2265.1995.tb02665.x

Cited by 72 publications

(36 citation statements)

References 18 publications

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“…The HA phenotype among PCOS sisters was similar biochemically to that found in ovulatory women with polycystic ovaries observed by ultrasound reported by a number of investigators (9,28,29). In our study, the HA sisters had a lower BMI than the PCOS sisters.…”

Section: Discussionsupporting

confidence: 90%

Evidence for a genetic basis for hyperandrogenemia in polycystic ovary syndrome

Legro¹,

Driscoll

Strauss

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

643

415

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Our preliminary family studies have suggested that some female first-degree relatives of women with polycystic ovary syndrome (PCOS) have hyperandrogenemia per se. It was our hypothesis that this may be a genetic trait and thus could represent a phenotype suitable for linkage analysis. To investigate this hypothesis, we examined 115 sisters of 80 probands with PCOS from unrelated families. PCOS was diagnosed by the combination of elevated serum androgen levels and <6 menses per year with the exclusion of secondary causes. The sisters were compared with 70 healthy age-and weight-comparable control women with regular menses, no clinical evidence of hyperandrogenemia, and normal glucose tolerance. Twenty-two percent of the sisters fulfilled diagnostic criteria for PCOS. In addition, 24% of the sisters had hyperandrogenemia and regular menstrual cycles. Circulating testosterone (T) and nonsex hormone-binding globulinbound testosterone (uT) levels in both of these groups of sisters were significantly increased compared with unaffected sisters and control women (P < 0.0001 for both T and uT). Probands, sisters with PCOS, and hyperandrogenemic sisters had elevated serum luteinizing hormone levels compared with control women. We conclude that there is familial aggregation of hyperandrogenemia (with or without oligomenorrhea) in PCOS kindreds. In affected sisters, only one-half have oligomenorrhea and hyperandrogenemia characteristic of PCOS, whereas the remaining one-half have hyperandrogenemia per se. This familial aggregation of hyperandrogenemia in PCOS kindreds suggests that it is a genetic trait. We propose that hyperandrogenemia be used to assign affected status in linkage studies designed to identify PCOS genes.Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies among women of reproductive age (1, 2). It has been proposed that PCOS has a genetic basis because a high number of female relatives are affected (1-5). These studies have been constrained by a failure to systematically examine PCOS women and their female relatives compared with concurrently studied control women to define precisely biochemical phenotypes. Indeed, most studies have evaluated relatives by questionnaires (3, 4), and this may have resulted in a miscalculation of the number of affected subjects. Other studies have used ovarian morphology (polycystic ovaries) rather than the endocrine abnormalities of the syndrome (hyperandrogenemia and chronic anovulation), to assign affected status (6, 7). The polycystic ovary morphology, however, can be present in ovulatory women with hyperandrogenemia (8) and in women who are endocrinologically normal (9).Our preliminary family studies have suggested that some female first-degree relatives of PCOS probands have hyperandrogenemia per se (1, ʈ ). It is our hypothesis that the endocrine abnormalities of PCOS have a genetic basis and that hyperandrogenemia may be an additional phenotype (1, 10, ʈ ). In preparation for linkage studies to identify PCOS genes, we sought to determin...

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Section: Discussionsupporting

confidence: 90%

Evidence for a genetic basis for hyperandrogenemia in polycystic ovary syndrome

Legro¹,

Driscoll

Strauss

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

643

415

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show abstract

“…The ovarian androgen response is exaggerated in women with PCOS following stimulation by exogenous human chorionic gonadotrophin (hCG) (Gilling-Smith et al 1997) or by endogenous gonadotrophin (after treatment with exogenous gonadotrophin-releasing-hormone (GnRH) analogue) (Ehrmann et al 1995, White et al 1995. A pronounced ovarian androgen response is also evoked by exogenous hCG in adult female rhesus monkeys, androgenized prenatally (Eisner et al 2002).…”

Section: Evidence For a Primary Ovarian Disorder Affecting Androgen Pmentioning

confidence: 99%

“…Nevertheless, results from recent experiments using animal models, together with supporting clinical evidence, lead us to propose that the development of PCOS is a linear process with an origin before adolescence (the contemporary clinical perception of age of onset of PCOS). Superimposed on this developmental process are interacting genetic and environmental factors that may alter phenotypic expression of PCOS during adult life, particularly the susceptibility to anovulation (White et al 1995, Franks et al 1997, Chang et al 2000.…”

Section: Introductionmentioning

confidence: 99%

Developmental origin of polycystic ovary syndrome - a hypothesis

Abbott

Dumesic²,

Franks

2002

Journal of Endocrinology

444

255

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Polycystic ovary syndrome (PCOS) is a common but complex endocrine disorder and is a major cause of anovulation and consequent subfertility. It is also associated with a metabolic disturbance, characterized by hyperinsulinaemia and insulin resistance that carries an increased risk of type 2 diabetes in later life. Despite its prevalence little is known about its aetiology, but there is increasing evidence for an important genetic involvement. On the basis of experimental observations in the prenatally androgenized sheep and rhesus monkey, and supported by data from human studies, we propose that the clinical and biochemical features of PCOS can arise as a consequence of genetically determined hypersecretion of androgens by the ovary during, or very likely long before, puberty. The resulting hyperandrogenism results in 'programming' of the hypothalamic-pituitary unit to favour excess LH secretion, and encourages preferential abdominal adiposity that predisposes to insulin resistance. The severity of hyperinsulinaemia and insulin resistance (which has a profound influence on the phenotype of PCOS) is further influenced by both genetic factors (such as polymorphism in the insulin gene regulatory region) and environmental factors, notably obesity. This hypothesis therefore suggests a unifying, 'linear' model to explain the aetiology of the heterogeneous phenotype.

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“…mostraram que a anormalidade da esteroidogênese demonstrada em pacientes portadoras de HOF não estava relacionada exclusivamente ao excesso de LH (9). Postularam que a hiperinsulinemia poderia ter um papel importante nesta disfunção, considerando que a diminuição da sensibilidade à insulina foi demonstrada tanto na SOP quanto no HOF (20) e que este hormônio potencializa a ação do LH (24). A insulina, possivelmente agindo através do sistema IGF-I, aumenta a concentração do mensageiro do ácido ribonuclêico e das enzimas da reação limite da esteroidogênese, contidas no citocromo P450scc, antagonizando a downregulation induzida pelo LH.…”

Section: Discussionunclassified

“…A sín -drome é funcional por 2 razões: não há necessidade de demonstração anatômica típica para caracterizá-la e é gonadotrofina-dependente. De fato, enquanto o cateterismo do plexo venoso ovariano em pacientes com SOP tenha demonstrado uma produção excessiva de andró -genos (4), a supressão da secreção de gonadotrofinas, através da administração crônica do hormônio liberador de gonadotrofinas, corrigiu a hiperandrogenemia (5).…”

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Avaliação da utilidade do estímulo agudo das gonadotrofinas e dos esteróides ovarianos com análogo do hormônio liberador de gonadotrofinas no diagnóstico diferencial do hiperandrogenismo ovariano funcional

Normando

Wajchenberg

Hayashida

et al. 2003

Arq Bras Endocrinol Metab

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A resposta da 17-hidroxiprogesterona (17OHP) ao estímulo agudo com um análogo do hormônio liberador de gonadotrofinas (GnRHa) e sua relação com a sensibilidade à insulina (SI) foi avaliada em 8 mulheres voluntárias normais e obesas (grupo N), com idades entre 24 e 40 anos (mediana de 29) e índice de massa corpóreo (IMC) entre 32,0 e 46,5kg/m 2 (mediana de 35,7) e 8 pacientes portadoras da síndrome dos ovários policísticos (grupo SOP) com idades entre 19 e 28 anos (mediana de 26) e IMC entre 30,1 e 40,1kg/m 2 (mediana de 35,8), submetidas a estímulo agudo com acetato de leuprolide, 10µg/kg SC e a teste de tolerância oral à glicose (TTOG). Observou-se aumento significativo da concentração de 17OHP, tanto no grupo N (1,5 vs. 2,9ng/mL; p= 0,023) quanto no grupo SOP (0,8 vs. 3,1ng/mL; p= 0,007), não havendo diferença significativa entre os grupos. A SI foi avaliada através da área sob a curva de insulina (ASCI) no TTOG. O grupo N apresentou ASCI significativamente menor que o grupo SOP (14.384 vs. 22.800µUI/mL/min, p= 0,04). Não houve correlação entre a concentração de 17OHP após estí -mulo e a ASCI. The response of 17-hydroxyprogesterone (17OHP) to gonadotropinreleasing hormone analogue (GnRHa) acute stimulation and its relationship to insulin sensitivity (IS) were evaluated in 8 normal obese voluntary women (group N), aged 24 to 40 years (median 29) and body mass index (BMI) of 32.0 to 46.5kg/m 2 (median of 35.7), and 8 patients with polycystic ovary syndrome (group PCOS) aged 19 to 28 years (median of 26) and BMI of 30.1 to 40.1kg/m 2 (median of 35.8), submitted to an acute stimulation with leuprolide acetate 10µg/kg and to am oral glucose tolerance test. We observed a significant increase of 17OHP levels in group N (1.5 vs. 2.9ng/mL; p= 0.023) as well as in group PCOS (0.8 vs. 3.1ng/mL; p = 0.007), with no significant difference between both groups. The area under the curve of insulin (AUCI) was significantly less in the group N (14,384 vs. 22,800mUI/mL/min, p= 0,04). There was no correlation between 17OHP and the AUCI. (Arq Bras Endocrinol Metab 2003;47/1:55-61)

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Gonadotrophin and gonadal steroid response to a single dose of a long‐acting agonist of gonadotrophin‐releasing hormone in ovulatory and anovulatory women with polycystic ovary syndrome

Cited by 72 publications

References 18 publications

Evidence for a genetic basis for hyperandrogenemia in polycystic ovary syndrome

Evidence for a genetic basis for hyperandrogenemia in polycystic ovary syndrome

Developmental origin of polycystic ovary syndrome - a hypothesis

Avaliação da utilidade do estímulo agudo das gonadotrofinas e dos esteróides ovarianos com análogo do hormônio liberador de gonadotrofinas no diagnóstico diferencial do hiperandrogenismo ovariano funcional

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