Objective: There is no universal consensus as to the criteria of PCOS (i.e. Rotterdam ESHRE/ASRM versus Androgen Excess Society (AES) criteria). Furthermore, androgen measurements within the female range are fraught with several methodological problems. As GnRH stimulation can reveal a relative LH excess, caused by an increased frequency of hypothalamic GnRH pulses, then we have endeavoured to assess gonadotrophin response to GnRH in women with PCOS and healthy controls.
Design, patients and methods: The study involved 155 subjects: PCOS (Rotterdam criteria), n=121, age (mean±S.D.) 24.8±5.4 years, BMI 24.5±6.0 kg/m2, all with oligo-/amenorrhoea and polycystic ovarian morphology, and 34 regularly menstruating controls, matched for age and BMI, with normal ovarian morphology. Total testosterone, androstendione, DHEAS, 17OH-progesterone and prolactin were measured in early follicular phase. LH and FSH were measured before and at 30 and 60 min after GnRH stimulation (100 μg i.v.). Insulin resistance was assessed by HOMA and Insulin Resistance Index derived from glucose and insulin during 75g OGTT.
Results: As expected women with PCOS had higher androgens and were more insulin resistant. Fifty-four (41.9%) women with PCOS had, however, all androgens within the reference range, and thus would fulfil the Rotterdam, but not the AES criteria for diagnosis of PCOS. Baseline and GnRH-stimulated LH concentrations were higher in PCOS (9.09±5.56 vs 4.83±1.71 IU/l, 35.48±31.4 vs 16.30±6.68 IU/l, 33.86±31.8 vs 13.45±5.2 IU/l, at 0, 30 and 60 min. post GnRH, respectively, P<0.0001). An LH/FSH ratio in PCOS group increased further after GnRH stimulation (P<0.01). ROC analysis revealed that LH30min/FSH30min>2.11 or LH60min/FSH60min>1.72 had 78.3 and 87.5% sensitivity and 81.7 and 81.3% specificity for the diagnosis of PCOS. In contrast, both baseline and GnRH-stimulated LH and FSH concentrations were no different in women with PCOS and raised androgens versus those with androgens within the reference range (P=0.71 and P=0.20 for LH and FSH, respectively). Both these groups, however, had higher LH levels and higher baseline and GnRH-stimulated LH/FSH ratio than controls (P<0.001).
Conclusions: Regardless of their androgen status, women with polycystic ovarian morphology and oligo-/amenorrhoea have higher baseline and GnRH-stimulated LH concentrations and higher GnRH-stimulated LH/FSH ratio in comparison to healthy controls. This suggests the existence of similar underlying mechanism accounting for menstrual irregularities. In our opinion these observations support clinical validity of diagnostic criteria for PCOS based on the Rotterdam consensus.