GnRH test as an additional investigation in the diagnosis of polycystic ovary syndrome (PCOS): potential application of stimulated LH/FSH ratio
Agata Cajdler-Luba1, Krzysztof Lewandowski1, Malgorzata Bienkiewicz2, Ireneusz Salata1 & Andrzej Lewinski1
Diagnosis of PCOS may be sometimes difficult, e.g. due to limited sensitivity of androgen assays and discrepancies in interpretation of ovarian ultrasound imaging. As GnRH stimulation test can reveal a relative LH excess, then we have endeavoured to assess whether this test might be useful in the diagnosis of PCOS.
Patients and methods: The study involved 154 subjects: PCOS group, n=120, age (mean±S.D.) 24.8±5.4 years, BMI 24.5±6.0 kg/m2 and regularly menstruating controls, n=34, age 26.6±5.0 years, BMI 24.6±5.5 kg/m2. All subjects had pelvic ultrasound as well as total testosterone, androstendione, DHEAS, 17OH-progesterone, thyroid hormones and prolactin measured (early follicular phase). LH and FSH were measured before (0 min) 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 OGTT).
Results: PCOS women and controls were matched for age and BMI, but had higher testosterone (P=0.0002), androstendione (P=0.0021), 17OH-progesterone (P<0.0001) and were more insulin resistant. Baseline and 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). There was no difference between baseline and stimulated FSH concentrations between groups. Relative increases of LH or FSH (i.e. LH30 min/LH0 min, LH60 min/LH0 min, FSH30 min/FSH0 min, FSH60 min/FSH0 min) were similar in both groups. There was, however, a marked increase in LH/FSH ratio in PCOS in comparison to controls (LH0 min/FSH0 min 1.59±0.95 vs 0.76±0.2, LH30 min/FSH30 min 4.07±3.0 vs 1.89±0.79, LH60 min/FSH60 min 3.56±2.58 vs 1.55±0.63, P<0.0001 at all time points). Further analysis revealed that LH30 min/FSH30 min>2.0 or LH60 min/FSH60 min>1.7 had 79 and 83% sensitivity and 72 and 75% specificity for the diagnosis of PCOS, respectively. In contrast LH0 min/FSH0 min>2.0 had only 23% sensitivity, while total testosterone, and androstendione had 38.6%, 34.7% sensitivity, respectively.
Conclusions: Our study indicates that raised LH/FSH ratio after GnRH stimulation might be potentially useful as an additional diagnostic tool in the diagnosis of PCOS.