PCOS
Posted: 06 Oct 2012, 00:01
Endocrine features
The heterogeneity of the clinical features of PCOS extends to the endocrine abnormalities associated with it As a result, specific endocrine parameters are not a requirement for diagnosis, although measurement can be helpful to support it and, importantly, to exclude other conditions. Until the advent of widely available high-resolution ultrasonography, the diagnosis of PCOS was usually based on a combination of biochemical and clinical features.
Raised serum testosterone concentration is the most common biochemical abnormality in PCOS, occurring in about 70% of cases. The free androgen index, calculated from total testosterone and sex-hormone binding globulin (SHBG), has been found to be a useful marker by some clinicians. However, since SHBG is closely associated with BMI and, more particularly, abdominal circumference, the increased free androgen index found in PCOS is at least in part a reflection of increased abdominal adiposity. Serum concentrations of the weak androgen androstenedione are also elevated in PCOS. In practical terms, measuring serum testosterone is usually preferable to measuring androstenedione, as the process is automated in most clinical laboratories and therefore more cost-efficient. In 10 to 20% of patients with PCOS, serum levels of the weak adrenal androgen dehydroepiandrosterone sulphate (DHEAS) are also modestly elevated, suggesting that, at least in some patients with PCOS, there may be an adrenal contribution to increased circulating androgens.
Among women with PCOS, clinical signs of hyperandrogenaemia (e.g. hirsutism) are associated with higher testosterone levels than in those without. The presence or absence of features of hyperandrogenism, however, does not accurately predict serum androgen levels, as clinical expression depends on the peripheral conversion of testosterone to its active metabolite 5α-dihydrotestosterone by 5α-reductase, as well as on end-organ sensitivity (androgen receptor activity) (see ‘Other causes of hyperandrogenism in women’, below). Obesity in PCOS is associated with higher free testosterone levels than in lean counterparts, and in part reflects the lower SHBG levels found in the former group. In addition, obesity may have an independent effect on peripheral androgen metabolism since androsterone glucuronide levels, a marker for peripheral 5α-reductase activity, are raised in this group. Genetic factors may affect end-organ sensitivity, e.g. PCOS occurs in Chinese and Japanese women, but hirsutism is relatively uncommon in these populations. By contrast, hirsutism features commonly in women with PCOS from the Indian subcontinent.
Women with PCOS tend to have higher LH levels than those with normal ovaries. The highest prevalence of elevated LH levels is in those with anovulatory menses or amenorrhoea, but even in this group more than 40% will have normal LH. By contrast, FSH levels are normal but tend to be lower than in the normal early follicular phase. Many have cited a raised LH:FSH ratio (either 2.5:1 or 3:1) as a diagnostic feature of PCOS, but it is neither sensitive nor specific enough to be used as a reliable diagnostic criterion.
Oestrogen levels in women with all variants of PCOS are normal. As discussed previously, this can be used to distinguish between oligo/amenorrhoeic women with PCOS and those with other causes of anovulation such as hypothalamic or pituitary disorders, or ovarian failure. Plasma oestradiol levels in PCOS lie within the range normally seen in the early to mid follicular phase of the menstrual cycle, but oestrone levels are significantly higher. This is probably because of the increased peripheral conversion of high levels of circulating androstenedione to oestrone in adipose tissue.
Hyperprolactinaemia has been described in association with PCOS, but this usually reflects spurious fluctuations in serum prolactin; it probably occurs no more commonly than in the normal population and is rarely a persistent problem.
The heterogeneity of the clinical features of PCOS extends to the endocrine abnormalities associated with it As a result, specific endocrine parameters are not a requirement for diagnosis, although measurement can be helpful to support it and, importantly, to exclude other conditions. Until the advent of widely available high-resolution ultrasonography, the diagnosis of PCOS was usually based on a combination of biochemical and clinical features.
Raised serum testosterone concentration is the most common biochemical abnormality in PCOS, occurring in about 70% of cases. The free androgen index, calculated from total testosterone and sex-hormone binding globulin (SHBG), has been found to be a useful marker by some clinicians. However, since SHBG is closely associated with BMI and, more particularly, abdominal circumference, the increased free androgen index found in PCOS is at least in part a reflection of increased abdominal adiposity. Serum concentrations of the weak androgen androstenedione are also elevated in PCOS. In practical terms, measuring serum testosterone is usually preferable to measuring androstenedione, as the process is automated in most clinical laboratories and therefore more cost-efficient. In 10 to 20% of patients with PCOS, serum levels of the weak adrenal androgen dehydroepiandrosterone sulphate (DHEAS) are also modestly elevated, suggesting that, at least in some patients with PCOS, there may be an adrenal contribution to increased circulating androgens.
Among women with PCOS, clinical signs of hyperandrogenaemia (e.g. hirsutism) are associated with higher testosterone levels than in those without. The presence or absence of features of hyperandrogenism, however, does not accurately predict serum androgen levels, as clinical expression depends on the peripheral conversion of testosterone to its active metabolite 5α-dihydrotestosterone by 5α-reductase, as well as on end-organ sensitivity (androgen receptor activity) (see ‘Other causes of hyperandrogenism in women’, below). Obesity in PCOS is associated with higher free testosterone levels than in lean counterparts, and in part reflects the lower SHBG levels found in the former group. In addition, obesity may have an independent effect on peripheral androgen metabolism since androsterone glucuronide levels, a marker for peripheral 5α-reductase activity, are raised in this group. Genetic factors may affect end-organ sensitivity, e.g. PCOS occurs in Chinese and Japanese women, but hirsutism is relatively uncommon in these populations. By contrast, hirsutism features commonly in women with PCOS from the Indian subcontinent.
Women with PCOS tend to have higher LH levels than those with normal ovaries. The highest prevalence of elevated LH levels is in those with anovulatory menses or amenorrhoea, but even in this group more than 40% will have normal LH. By contrast, FSH levels are normal but tend to be lower than in the normal early follicular phase. Many have cited a raised LH:FSH ratio (either 2.5:1 or 3:1) as a diagnostic feature of PCOS, but it is neither sensitive nor specific enough to be used as a reliable diagnostic criterion.
Oestrogen levels in women with all variants of PCOS are normal. As discussed previously, this can be used to distinguish between oligo/amenorrhoeic women with PCOS and those with other causes of anovulation such as hypothalamic or pituitary disorders, or ovarian failure. Plasma oestradiol levels in PCOS lie within the range normally seen in the early to mid follicular phase of the menstrual cycle, but oestrone levels are significantly higher. This is probably because of the increased peripheral conversion of high levels of circulating androstenedione to oestrone in adipose tissue.
Hyperprolactinaemia has been described in association with PCOS, but this usually reflects spurious fluctuations in serum prolactin; it probably occurs no more commonly than in the normal population and is rarely a persistent problem.