Effects of a monophasic combined oral contraceptive containing nomegestrol acetate and 17β-oestradiol in comparison to one containing levonorgestrel and ethinylestradiol on markers of endocrine function

Figures & data

Figure 1. Flow chart of participants. NOMAC/E2, nomegestrol acetate/17β-oestradiol; LNG/EE, levonorgestrel/ethinylestradiol.

Table 1 Summary of participants’ characteristics at screening

	NOMAC/E2 (n = 60)	LNG/EE (n = 58)	Total (n = 118)
Age (years), mean (SD)	28.2 (8.2)	29.1 (7.8)	28.7 (8.0)
Race, n (%)
Black	1 (1.7)	0	1 (0.8)
White	59 (98.3)	58 (100.0)	117 (99.2)
Weight (kg), mean (SD)	62.8 (9.7)	61.7 (9.0)	62.3 (9.3)
BMI (kg/m^2), mean (SD)	23.0 (2.9)	22.3 (2.5)	22.7 (2.7)
Parity, n (%)
Never pregnant	35 (58.3)	34 (58.6)	69 (58.5)
No pregnancy ≥ 28 weeks	4 (6.7)	3 (5.2)	7 (5.9)
1	7 (11.7)	6 (10.3)	13 (11.0)
≥ 2	14 (23.3)	15 (25.9)	29 (24.6)
Last contraceptive method used within three months prior to screening*, n (%)
None	1 (1.7)	4 (6.9)	5 (4.2)
Combined oral contraceptive	19 (31.7)	22 (37.9)	41 (34.7)
Progestogen-only-pill	3 (5.0)	1 (1.7)	4 (3.4)
IUD (hormonal)	5 (8.3)	1 (1.7)	6 (5.1)
IUD (non-hormonal)	1 (1.7)	2 (3.4)	3 (2.5)
Vaginal ring or transdermal patch	5 (8.3)	7 (12.1)	12 (10.2)
Foam, condom, suppositories, diaphragm	26 (43.3)	21 (36.2)	47 (39.8)
Smoking status
Smokers, n (%)	14 (23.3)	7 (12.1)	21 (17.8)
Non-smokers, n (%)	46 (76.7)	51 (87.9)	97 (82.2)

*Most important contraceptive method.

NOMAC/E2, nomegestrol acetate/17β-oestradiol; LNG/EE, levonorgestrel/ethinylestradiol; SD, standard deviation; BMI, body mass index; NA, not applicable; IUD, intrauterine device.

Table 2 Effects of nomegestrol acetate/17β-oestradiol and levonorgestrel/ethinylestradiol on adrenal and thyroid indices

		Nomegestrol acetate/17β-oestradiol				Levonorgestrel/ethinylestradiol
Index	Assessment	Mean	SD	Median	IQR	Mean	SD	Median	IQR
Total cortisol (nmol/l)	Baseline	482	129	469	166	502	153	524	166
	Cycle 3	610	186	607	221	975	215	1021	248
	Cycle 6	608	167	580	193	944	183	952	207
	Change from baseline to cycle 6	123	195	111	166	432	172	441	193
	% change from baseline to cycle 6	32.9	45.3	24.9	39.8	97.4	65.2	82.2	52.8
CBG (nmol/l)	Baseline	910	201	867	232	932	163	917	213
	Cycle 3	1182	367	1091	326	2086	430	2069	588
	Cycle 6	1116	253	1053	253	1980	389	1929	536
	Change from baseline to cycle 6	220	264	194	225	1047	402	967	523
	% change from baseline to cycle 6	27.4	29.2	21.9	28.9	117.7	53.4	111.0	81.0
TSH (mU/l)	Baseline	2.69	1.28	2.38	1.61	2.20	1.08	1.92	1.12
	Cycle 3	3.03	1.52	2.71	1.77	3.78	10.23	2.52	1.61
	Cycle 6	2.96	2.05	2.56	1.70	2.75	3.36	2.19	0.96
	Change from baseline to cycle 6	0.25	1.75	− 0.04	1.16	0.50	3.07	0.11	0.91
	% change from baseline to cycle 6	13.3	63.6	− 2.2	50.6	22.8	78.5	6.9	49.7
Free T4 (pmol/l)	Baseline	14.0	1.6	14.0	1.9	14.1	1.5	14.0	2.2
	Cycle 3	15.5	1.9	15.2	3.0	15.7	2.1	15.8	2.9
	Cycle 6	15.9	2.0	15.8	2.5	15.7	2.1	15.3	3.3
	Change from baseline to cycle 6	1.8	1.8	1.7	2.7	1.4	1.7	1.3	2.1
	% change from baseline to cycle 6	13.4	13.8	11.8	19.1	10.2	11.9	9.5	14.2
TBG (mg/l)	Baseline	20.3	2.9	20.1	4.1	20.3	3.3	20.1	4.4
	Cycle 3	24.0	2.8	24.4	3.8	28.1	4.7	28.2	6.8
	Cycle 6	24.2	3.6	24.0	3.6	28.4	5.3	27.9	7.4
	Change from baseline to cycle 6	4.0	3.9	4.3	4.0	7.9	3.8	7.7	5.4
	% change from baseline to cycle 6	21.6	20.6	21.0	23.2	39.0	19.5	38.1	30.2

SD, standard deviation; IQR, interquartile range; CBG, corticosteroid-binding globulin; TSH, thyroid-stimulating hormone; T₄, thyroxine; TBG, thyroxine-binding globulin.

Table 3 Effects of nomegestrol acetate/17β-oestradiol and levonorgestrel/ethinylestradiol on androgenic indices

		Nomegestrol acetate/17β-oestradiol				Levonorgestrel/ethinylestradiol
Index	Assessment	Mean	SD	Median	IQR	Mean	SD	Median	IQR
Total testosterone (nmol/l)	Baseline	1.68	0.75	1.58	1.13	1.90	0.94	1.82	0.97
	Cycle 3	1.12	0.60	1.04	0.77	0.91	0.56	0.89	0.80
	Cycle 6	1.23	0.86	1.04	0.77	0.91	0.58	0.80	0.71
	Change from baseline to cycle 6	− 0.47	0.83	− 0.46	0.79	− 1.02	0.72	− 0.88	0.81
	% change from baseline to cycle 6	− 25.2	38.1	− 31.1	42.8	− 53.8	25.4	− 60.2	29.2
Free testosterone (pmol/l)	Baseline	24.5	14.9	20.8	13.9	26.3	16.6	24.3	17.3
	Cycle 3	12.3	6.4	10.4	10.5	10.0	6.7	10.4	10.4
	Cycle 6	12.8	8.8	10.4	7.0	9.9	6.7	6.9	10.4
	Change from baseline to cycle 6	− 12.2	13.6	− 10.4	10.4	− 16.6	14.0	− 13.9	15.7
	% change from baseline to cycle 6	− 41.5	39.4	− 50.4	33.5	− 57.8	29.4	− 66.5	25.0
DHEAS (μmol/l)	Baseline	4.9	2.2	4.6	2.6	5.2	2.3	5.0	3.0
	Cycle 3	4.5	2.0	4.3	2.7	4.3	2.1	4.0	2.7
	Cycle 6	4.3	1.8	4.2	1.8	4.0	1.9	3.5	2.2
	Change from baseline to cycle 6	− 0.7	1.6	− 0.7	1.3	− 1.3	1.2	− 1.1	1.2
	% change from baseline to cycle 6	− 10.1	23.9	− 14.0	27.9	− 22.9	18.0	− 24.8	15.9
Androstenedione (nmol/l)	Baseline	9.6	3.5	9.0	4.1	10.3	3.9	9.4	4.4
	Cycle 3	7.6	2.5	7.5	2.8	6.5	2.7	6.3	3.3
	Cycle 6	8.2	3.0	8.1	3.6	7.0	3.4	6.3	4.5
	Change from baseline to cycle 6	− 1.7	3.0	− 1.4	3.6	− 3.6	3.2	− 4.0	3.7
	% change from baseline to cycle 6	− 13.2	30.2	− 15.5	37.3	− 33.0	27.3	− 36.4	33.3
DHT (nmol/l)	Baseline	0.59	0.21	0.55	0.23	0.62	0.26	0.52	0.34
	Cycle 3	0.61	0.25	0.58	0.27	0.47	0.21	0.47	0.31
	Cycle 6	0.53	0.28	0.48	0.38	0.36	0.19	0.33	0.26
	Change from baseline to cycle 6	− 0.08	0.30	− 0.14	0.41	− 0.28	0.26	− 0.28	0.34
	% change from baseline to cycle 6	− 7.3	47.7	− 22.6	71.8	− 38.1	37.8	− 48.3	38.4

SD, standard deviation; IQR, interquartile range; DHEAS, dehydroepiandrosterone sulphate; DHT, dihydrotestosterone.

Table 4 Effects of nomegestrol acetate/17β-oestradiol and levonorgestrel/ethinylestradiol on SHBG

		Nomegestrol acetate/17β-oestradiol				Levonorgestrel/ethinylestradiol
Index	Assessment	Mean	SD	Median	IQR	Mean	SD	Median	IQR
SHBG (nmol/l)	Baseline	73.5	34.3	65.5	33.6	77.5	26.2	76.5	40.6
	Cycle 3	101.4	37.1	96.3	55.5	103.7	35.5	93.9	47.6
	Cycle 6	108.2	43.6	107.9	57.8	99.8	31.5	98.3	30.8
	Change from baseline to cycle 6	35.3	41.4	33.8	52.0	20.7	30.4	15.3	42.6
	% change from baseline to cycle 6	61.7	67.0	44.1	78.8	36.4	53.3	22.4	64.1

SD, standard deviation; IQR, interquartile range; SHBG, sex hormone-binding globulin.

Table 5 Differences between treatment groups (nomegestrol acetate/17β-oestradiol versus levonorgestrel/ethinylestradiol) in median absolute changes from baseline to cycle 6 for adrenal, thyroid, and androgenic indices

	Difference in change from baseline to cycle 6 NOMAC/E2 vs. LNG/EE
Index	Estimate (95% CI)*	p-value**
Adrenal and thyroid indices
Total cortisol (nmol/l)	− 303 (− 359; − 248)	< 0.001
CBG (nmol/l)	− 811 (− 945; − 689)	< 0.001
TSH (mU/l)	− 0.10 (− 0.46; 0.27)	0.57
Free T4 (pmol/l)	0.45 (− 0.30; 1.10)	0.18
TBG (mg/l)	− 3.60 (− 5.20; − 2.20)	< 0.001
Androgens and androgen precursors
Total testosterone (nmol/l)	0.49 (0.28; 0.69)	< 0.001
Free testosterone (pmol/l)	3.50 (0.00; 7.00)	0.13
DHEAS (μmol/l)	0.63 (0.16; 1.07)	0.013
Androstenedione (nmol/l)	1.96 (0.87; 3.24)	< 0.001
DHT (nmol/l)	0.20 (0.08; 0.31)	< 0.001
Other Index
SHBG (nmol/l)	15.6 (3.2, 28.8)	0.019

*Point estimates of the difference and two-sided 95% confidence intervals (CIs) by the Hodges-Lehmann approach.

**Differences between groups; Cochran-Mantel-Haenszel test adjusted for age class using standardised midranks, applied on changes from baseline.

NOMAC/E2, nomegestrol acetate/17β-oestradiol; LNG/EE, levonorgestrel/ethinylestradiol; CBG, corticosteroid-binding globulin; TSH, thyroid-stimulating hormone; T₄, thyroxine; TBG, thyroxine-binding globulin; DHEAS, dehydroepiandrosterone sulphate; DHT, dihydrotestosterone; SHBG, sex hormone-binding globulin.