Comparison between creatinine and pregnanediol adjustments in the retrospective analysis of urinary hormone profiles during the human menstrual cycle

Abstract

Measurement of reproductive hormones in urine is a practical way of obtaining large amounts of information; however, there is still controversy on how to overcome problems derived from volume fluctuations between samples. Creatinine adjustment is a widely accepted solution, however, it introduces an extra cost, and large studies involving multiple sequential determinations would benefit from more economical solutions. We determined the value of creatinine adjustment, and compared it with a mathematical method that uses the smoothed profile of pregnanediol (PdG) as a reference to adjust other hormonal markers. To do this, we investigated the effects on three major urinary reproductive hormonal markers (luteinizing hormone (LH), estrone 3-glucuronide (E1G) and PdG) in 17 complete menstrual cycles. Detection of the day of LH peak did not differ between raw and adjusted data. Creatinine adjustment reduced variation in pre-ovulatory E1G levels between individuals, though the effect was negligible within individuals. No significant differences were found regarding post-ovulatory PdG rise. Although creatinine adjustment significantly reduces variability, producing smoother profiles, an equivalent degree of smoothness is obtained using the PdG adjustment. We conclude that under the current technology, for the retrospective study of urinary hormonal profiles in the human menstrual cycle, PdG adjustment is a valid alternative to creatinine.

Sequential classification of endocrine stages during reproductive aging in women: the FREEDOM study*

“…21,41 The sensitivity for each analyte was 0.17 IU/L for FSH, 0.09 IU/L for LH, 0.1 ng/mL for E1G, and 0.07 mg/mL for PdG. For the FSH assay, the intra-assay coefficients of variation (CVs) were 5.1%, 2.4%, and 1.8% for concentrations of 1.8, 8.2, and 42.9 IU/L, respectively, and the respective interassay CVs at the same concentrations were 4.0%, 3.4%, and 2.4%.…”

“…41 Briefly, a smooth curve was fitted to log (PdG) and the residuals were used to adjust the concentrations of the other hormones. This was achieved by using the SAS/IML Splinec routine with a smoothing parameter of 10.…”

“…This was achieved by using the SAS/IML Splinec routine with a smoothing parameter of 10. 41,42 FSH and LH results are expressed as units per liter (IU/L), E1G as nanograms per milliliter (ng/mL), and PdG as micrograms per milliliter (mg/mL).…”

Oestradiol treatment restores the capacity of castrated males to induce both the Vandenbergh and the Bruce effects in mice (Mus musculus)

“…However, this practice has been criticised by some as unnecessary or misleading (e.g. Alessio et al 1985, Hakim et al 1994, Miro et al 2004. Moreover, urinary creatinine can be dynamic in social situations in mice, decreasing substantially in conjunction with polyuria and polydipsia in males housed nearby females ).…”

Combined oral contraceptives in women with menstrual migraine without aura

“…Because hormonal contraceptive use is also prevalent in this group, clinicians are often questioned about the use of hormonal birth control in women with coexisting headaches. Women with menstrual migraines, a subset category of migraines without aura, have migraine attacks specifically during the menstrual period that are thought to be related to the decline in estrogen levels during the late luteal phase, with the consequent increase in prostaglandin release during menses (11,12).…”