RESUMEN
Low-dose, step-up gonadotropin is the treatment of choice for women with polycystic ovary syndrome (PCOS) who have not conceived after anti-oestrogen treatment and as an effective alternative to pulsatile GnRH in women with hypogonadotropic hypogonadism (HH). There has been, however, no large-scale, comparative study between the two groups using low-dose gonadotropins. Here, we performed a retrospective, comparative analysis, in a single clinic database, of efficacy and safety of induction of ovulation using low-dose gonadotropins in 364 women with PCOS and 80 women with HH. The rate of ovulation was high in both PCOS (83%) and HH (84%) but mono-follicular, ovulatory cycles were more prevalent in PCOS than in HH (77% vs 53%, P < 0.0001) and the proportion of cycles that were abandoned was higher in HH than in PCOS (25% vs 15%, P < 0.0001). The median threshold dose of gonadotropin required to induce ovulation was 75 IU/day in PCOS and 113 IU/day in HH (P < 0.001) and the range of doses was greater in HH women. Forty-nine percent of women with PCOS and 65% of those with HH conceived (more than 90% within 6 cycles of treatment) and had at least one pregnancy. Multiple pregnancies (all twins) occurred in only 4% of women with PCOS and 5% of those with HH. These findings emphasise the efficacy and safety of low-dose gonadotropin treatment for both clomiphene-resistant women with PCOS and those with HH. These results highlight the importance of choosing the more physiological approach of gonadotropin induction of ovulation in both groups as the most appropriate treatment, in preference to IVF.
Asunto(s)
Anovulación/tratamiento farmacológico , Fármacos para la Fertilidad Femenina/uso terapéutico , Fertilización In Vitro/métodos , Inducción de la Ovulación/métodos , Síndrome del Ovario Poliquístico/complicaciones , Adulto , Anovulación/etiología , Femenino , Humanos , EmbarazoRESUMEN
CONTEXT: Polycystic ovary syndrome (PCOS) is a common endocrinopathy of uncertain etiology but with strong evidence for a genetic contribution. OBJECTIVE: The objective of the study was to test the hypothesis that the typical polycystic ovarian morphology is a marker of inherited biochemical features in families of women with PCOS. DESIGN: A study of probands with PCOS and their sisters. PATIENTS: Patients included 125 probands and 214 sisters. All probands had PCOS, defined by symptoms of anovulation and/or hyperandrogenism with polycystic ovaries on ultrasound. Affected sisters were defined by polycystic ovaries, regardless of symptoms, and unaffected sisters defined by normal ovarian morphology. SETTING: This was a clinic-based study. MAIN OUTCOME MEASURES: Clinical, endocrine, and metabolic features in the various groups were compared, and estimates of broad-sense heritability were obtained using the quantitative transmission disequilibrium test. RESULTS: Although affected sisters had fewer symptoms than probands (30% had no symptoms of PCOS), serum testosterone, androstenedione, LH, and fasting insulin and insulin sensitivity were similar in the two groups with polycystic ovaries but significantly different from those in unaffected sisters or controls. We observed moderate to high heritabilities for all traits studied in affected sister pairs, whereas heritabilities calculated from discordant siblings were substantially lower. CONCLUSIONS: These data provide further evidence for a genetic basis of PCOS. The high heritability of biochemical features in probands and affected sisters, despite wide variation in symptoms, shows that not only are these biochemical traits strongly influenced by genetic factors but also, importantly, that polycystic ovarian morphology is an index of inherited traits in families with PCOS.
Asunto(s)
Biomarcadores/sangre , Ovario/patología , Síndrome del Ovario Poliquístico/patología , Carácter Cuantitativo Heredable , Hermanos , Adulto , Androstenodiona/sangre , Biomarcadores/análisis , Estudios de Casos y Controles , Femenino , Hirsutismo/sangre , Hirsutismo/complicaciones , Humanos , Persona de Mediana Edad , Oligomenorrea/sangre , Oligomenorrea/complicaciones , Tamaño de los Órganos , Ovario/diagnóstico por imagen , Síndrome del Ovario Poliquístico/sangre , Síndrome del Ovario Poliquístico/complicaciones , Síndrome del Ovario Poliquístico/diagnóstico por imagen , Testosterona/sangre , UltrasonografíaRESUMEN
Polycystic ovary syndrome accounts for more than 75% of cases of anovulatory infertility. The mechanism of anovulation is uncertain but there is evidence that arrested antral follicle development is associated with the abnormal endocrine profile, in particular the interaction of insulin and LH on granulosa cell differentiation. In terms of management, induction of ovulation can be achieved in most cases by the use of antiestrogens. Treatment of clomiphene-resistant subjects is difficult; conventional doses of gonadotropins are associated with high rates of ovarian hyperstimulation syndrome and multiple pregnancy. On the other hand, low-dose gonadotropin therapy has proven effective in inducing unifollicular ovulation and, in this review, we present, in detail, a recent analysis the results from this center. The cumulative conception rate after six cycles was more than 50% and, importantly, the multiple pregnancy rate was only 3%. Weight reduction in obese subjects with PCOS not only increases the chance of fertility but may also improve the long-term prognosis with regard to development of diabetes. Insulin-sensitizing drugs such as metformin may also have a place in treatment of PCOS.
Asunto(s)
Gonadotropinas/uso terapéutico , Infertilidad Femenina/complicaciones , Infertilidad Femenina/tratamiento farmacológico , Síndrome del Ovario Poliquístico/complicaciones , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Adulto , Anovulación/complicaciones , Anovulación/tratamiento farmacológico , Clomifeno/farmacología , Clomifeno/uso terapéutico , Femenino , Humanos , Metformina/farmacología , Metformina/uso terapéutico , Inducción de la Ovulación/métodos , Embarazo , Resultado del TratamientoRESUMEN
OBJECTIVE: Although androgenic alopecia is recognised to be a symptom of polycystic ovary syndrome (PCOS), it is not known whether polycystic ovaries (PCO) and associated endocrine abnormalities are present in patients who present with alopecia as a primary complaint. We therefore set out to determine the strength of the association between androgenic alopecia and PCO. We examined the prevalence of ultrasound-based polycystic ovarian morphology and associated clinical and biochemical features in a large multiethnic group of women whose presenting complaint was of alopecia, and in a control group. SUBJECTS AND METHODS: We studied 89 women of mixed ethnic origin with androgenic alopecia and compared them to 73 control women. A detailed history was taken, anthropometry was performed and assessment of body-hair distribution was made. The presence of PCO was established by pelvic ultrasound scan. Serum gonadotrophins, testosterone, androstenedione, dihydrotestosterone and sex hormone binding globulin concentrations were measured. RESULTS: Women with alopecia had a higher prevalence of PCO and hirsutism than the control population (PCO: 67% vs 27%, P<0.00001; hirsutism: 21% vs 4%, P=0.003). Women with alopecia (with or without PCO) had higher testosterone, androstenedione and free androgen index than controls, even though few had frankly abnormal androgens. CONCLUSIONS: These findings confirm an association between androgenic alopecia and PCO, and other symptoms of hyperandrogenaemia. Thus most women who present with androgenic alopecia as their primary complaint also have PCO and have indices of abnormal androgen production. Since PCO is a well known risk factor for development of type 2 diabetes, this association has important implications for long-term management.