New reference intervals for cortisol, cortisol binding globulin and free cortisol index in women using ethinyl estradiol

Figures & data

Figure 1. Results shown by subgroup. The group of women using an estrogen containing contraception was divided into subgroups depending on the daily dose of ethinyl estradiol (EE) in the contraception. In the subgroups of women using an oral contraceptive pill or a contraceptive intravaginal ring, the median value of s-cortisol increase with increasing daily dose of EE. N: Number of women in the subgroup; S-Cortisol: serum concentration of cortisol.

Table 1. Results. Reference intervals given as the 2.5 and 97.5 percentiles of the distribution of reference values, and the corresponding 90% confidence intervals for the reference limits.

	Nonestrogen group			Ethinyl estradiol group
	(NEEG)			(EEG)
n	Reference interval (median)		n	Reference interval (median)		p-value for median
	90% CI for 2.5 prc.	90% CI for 97.5 prc.		90% CI for 2.5 prc.	90% CI for 97.5 prc.
S-cortisol morning (8–10.30 am)
157	159–569 (318)		120	284–994 (667)		<0.001
	151–185	543–597		270–311	970–1064
S-CBG morning (8–10.30 am)
156	860–1940 (1101)		114	847–3366 (2188)		<0.001
	833–897	1513–2811		221–1339*	3201–3720*
S-FCI morning (8–10.30 am)
156	0.13–0.50 (0.28)		114	0.16–1.05 (0.29)		0.452
	0.06–0.16	0.47–0.59		0.16–0.17*	0.64–3.39

The median values and p-values from testing whether the medians were statistically significantly different in the two reference groups are also given.

* = Lower (respectively upper) confidence interval limit is held at the minimum (maximum) of sample values.

n: number of reference values; CI: Confidence interval; prc.: percentile; S-cortisol: Serum concentration of cortisol (nmol/L); S-CBG: Serum concentration of CBG (nmol/L); S-FCI: Free cortisol index in serum (s-cortisol/s-CBG).

Table 2. ‘Far-out’ values. The ‘far-out’ values as identified by Tukey’s method, with the values of the other relevant parameters.

‘Far-out’ value	Group	S-CBG	S-cortisol	S-FCI	Sa-cortisol (am)	Sa-cortisol (pm)
High s-CBG	NEEG	4189^a	230	0.06^b	21	4
High s-CBG	NEEG	2700^a	528	0.20	15	3
High s-CBG	NEEG	2411^a	441	0.18	–	–
Low s-CBG and high s-FCI	EEG (DD 30 µg)	222^b	753	3.39^a	11	8*
Low s-CBG and high s-FCI	EEG (DD 30 µg)	221^b	660	2.99^a	14	6

^a Values above the appropriate upper reference limit.

^b Values below the appropriate lower reference limit.

– Missing value.

* = <50% fall in sa-cortisol from the morning to the evening sample.

NEEG: Non ethinyl estradiol group; EEG: Ethinyl estradiol group; DD: Daily dose of ethinyl estradiol; S-CBG: Serum concentration of CBG (nmol/L); S-FCI: Free cortisol index in serum (s-cortisol/s-CBG); S-cortisol: Serum concentration of cortisol (nmol/L); Sa-cortisol: Salivary concentration of cortisol (nmol/L).