Adrenal Androgen Predictive Effects on Clinical andMetabolic Abnormalities of Polycystic Ovary Syndrome

Medeiros, Sebastião Freitas de; Barbosa, Bruna Barcelo; Medeiros, Matheus Antônio Souto de; Yamamoto, Ana Karine Lin Winck; Yamamoto, Márcia Marly Winck

doi:10.1055/s-0041-1741030

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Revista Brasileira de Ginecologia e Obstetrícia

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Sumário

Original Article • Rev. Bras. Ginecol. Obstet. 44 (02) • Feb 2022 • https://doi.org/10.1055/s-0041-1741030 copy

Adrenal Androgen Predictive Effects on Clinical andMetabolic Abnormalities of Polycystic Ovary Syndrome

Efeitos preditivos dos androgênios adrenais nas anormalidades clínicas e metabólicas da síndrome dos ovários policísticos

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Objective

To examine the possible effects of adrenal prohormones in the prediction of clinical and metabolic abnormalities in women with polycystic ovary syndrome (PCOS).

Methods

The present study enrolled 299 normal cycling non-PCOS, 156 normoandrogenemic, and 474 hyperandrogenemic women with PCOS. Baseline characteristics were compared using a chi-squared test or analysis of variance (ANOVA) as appropriate. The roles of adrenal prohormones and their ratios with total testosterone in predicting co-occurring morbidities in women PCOS were evaluated using univariate and multivariate logistic regression analyses.

Results

Adrenal hyperandrogenism per dehydroepiandrosterone sulfate (DHEAS) levels were found in 32% of women with PCOS. In non-PCOS women, dehydroepiandrosterone (DHEA) and its sulfate had no predictive role concerning clinical, anthropometric, and metabolic parameters. In PCOS women, mainly in the hyperandrogenemic group, DHEA showed to be a significant predictor against most anthropometric-metabolic index abnormalities (odds ratio [OR]=0.36-0.97; p<0.05), and an increase in triglycerides (TG) levels (OR=0.76; p=0.006). Dehydroepiandrosterone sulfate presented a few predictive effects regarding PCOS-associated disorders. In controls, DHEAS predicted against the increase in estimated average glucose (OR= 0.38; p=0.036). In the normoandrogenic group, it predicted against elevation in the waist/hip ratio (WHR) (OR= 0.59; p=0.042), and in hyperandrogenemic PCOS women, it predicted against abnormality in the conicity index (CI) (OR=0.31; p=0.028).

Conclusion

Dehydroepiandrosterone was shown to be a better predictor of abnormal anthropometric and biochemical parameters in women with PCOS than DHEAS. Thus, regarding adrenal prohormones, DHEA measurement, instead of DHEAS, should be preferred in PCOS management. The effects of androgen prohormones on the prediction of PCOS abnormalities are weak.

Keywords:
polycystic ovary syndrome; hyperandrogenism; obesity; hyperinsulinemia; metabolism

Variables	Non-PCOS	NA-PCOS	HA-PCOS
Age (years old)	29.9 ± 4.8^a	29.0 ± 5.2^a	27.0 ± 5.5^b
Ethnicity (n,%)^* * Comparisons using chi-squared or Fisher tests as appropriate.
Caucasian	267 (89.3)^a	113 (72.4)^b	335 (70.6)^b,^ Equal subscript letter denotes proportions that do not differ significantly from each other at the level of 0.05; otherwise, different letters indicate p < 0.05 between proportions or means ± standard deviation. NS= not significant.
African descendent	18 (6.0)^a	15 (9.6)^a	60 (12.7)^b
Other	14 (4.7)^a	28 (18.0)^b	79 (16.7)^b
Blood pressure (x̅ ± SD)^* ***** Comparisons using one-way analysis of variance.
SBP (mmHg)	113.1 ± 9.5^a	116.6 ± 72.1^b	120.0 ± 12.4^b
DBP (mmHg)	71.4 ± 9.0^a	74.6 ± 9.3^b	76.2 ± 9.3^b
Clinical signs (n,%)^* * Comparisons using chi-squared or Fisher tests as appropriate.
Acne	12 (4.0)^a	70 (44.9)^b	217 (45.7)^b
Hirsutism	7 (2.3)^a	72 (46.2)^b	224 (47.3)^b
Acanthosis	2 (0.7)^a	27 (17.3)^b	95 (20.0)^b
Striae	0 (0.0)^a	19 (12.2)^b	70 (14.7)^b
Galactorrhea	0 (0.0)^a	2 (1.3)^b	6 (1.3)^b
Metabolic disorders^* * Comparisons using chi-squared or Fisher tests as appropriate.
IFG	8 (2.6)^a	8 (5.1)^b	62 (13.1)^c
GI	11 (3.7)^a	16 (6.9)^b	78 (26.3)^c
T2DM	10 (3.3)^NS	5 (5.0)^NS	18 (6.0)^NS
Hormones^* * Comparisons using chi-squared or Fisher tests as appropriate.
DHEAS > 34nmol/l	32 (10.7)^a	8 (5.1)^a	32 (6.8)^a
DHEAS > 6.6µl/l	29 (9.7)^a	1 (0.6)^a	144 (31.8)^b
T > 1.75 mmol/l	30 (10.0)^a	11 (7.1)^a	328 (70.4)^b
FAI > 5.2	12 (4.0)^a	19 (12.2)^b	260 (61.3)^c

Variable	B	Wald	Sig	Exp B (Lower-Upper)	AUC	p-value
SBP (mmHg)	−0.424	1.761	0.184	0.655 (0.350–1.224)	0.842	< 0.001
DBP (mmHg)	−0.222	0.286	0.593	0.801 (0.355–1.808)	0.757	0.006
BW (kg)	0.950	4.247	0.039	2.584 (1.048–6.372)	0.976	< 0.001
WC (cm)	−0.206	0.385	0.535	0.814 (0.424–1.560)	0.957	< 0.001
WHR (ratio)	−0.295	0.627	0.429	0.745 (0.359–1.545)	0.697	0.019
FM (kg)	0.592	1.033	0.309	1.808 (0.577–5.667)	0.991	< 0.001
FM (%)	0.640	1.286	0.257	1.826 (0.628–5.726)	0.989	< 0.001
FM/LBM (ratio)	0.172	0.163	0.686	1.194 (0.505–2.824)	0.980	< 0.001
WTI	−0.107	0.169	0.681	0.898 (0.835–1.499)	0.789	< 0.001
CI (%,pg/ml, nmol/L)	−0.262	1.089	0.297	0.770 (0.471–1.258)	0.748	< 0.001
BSI	−0204	1.043	0.307	0.816 (0.552–1.206)	0.600	0.041
VAI	0.242	0.689	0.407	1.274(0.719–2.257)	0.734	< 0.001
LAP (cm, mmol/L)	−0.424	2.008	0.157	0.654 (0.364–1.177)	0.885	< 0.001
Go (mmol/L)	1.473	5.321	0.021	4.363 (1.248–15.257)	0.924	< 0.001
Io (pmol/L)	−0.069	3.742	0.053	0.9336 (0.820–1.001)	0.838	< 0.001
C-pep (pmol/L)	−0.455	3.182	0.074	0.635 (0.385–1.046)	0.780	< 0.001
HOMA-IR	0.095	0.089	0.766	1.100 (0.582–1.063)	0.784	< 0.001
HOMA %B	−0.544	4.740	0.029	0.581 (0.356–0.947)	0.739	< 0.001
eAG (mmol/L)	−0.075	0.089	0.765	0.928 (0.567–1.518)	0.638	0.027
TC (mmol/L)	0.010	0.001	0.971	1.010 (0.576–1.771)	0.554	0.293
HDL-C (mmol/L)	−0.025	0.793	0.373	0.975 (0.922–1.031)	0.700	< 0.001
LDL-C (mmol/L)	−0.135	0.255	0.613	0.874 (0.519–1.473)	0.552	0.431
VLDL-C (mmol/L)	0.009	0.054	0.816	1.009 (0.937–1.086)	0.732	< 0.001
TG (mmol/L)	0.025	0.567	0.452	1.026 (0.960–1.096)	0.722	< 0.001
DM	−0.072	0.517	0.472	0.931 (0.765–1.132)	0.868	0.006
IG	0.019	0.134	0.714	1.019 (0.920–1.129)	0.820	< 0.001

Variable	B	Wald	Sig	Exp B (Lower-Upper)	AUC	p-value
SBP (mmHg)	0.059	0.327	0.567	1.061 (0.866–1.300)	0.773	< 0.001
DBP (mmHg)	−0.098	0.559	0.455	0.907 (0.702–1.171)	0.751	< 0.001
BW (kg)	0.003	0.001	0.978	1.003 (0.794–1.268)	0.947	< 0.001
WC (cm)	−1.072	2.968	0.085	0.342 (1.101–1.159)	0.957	< 0.001
WHR	−0.189	2.429	0.119	0.828 (0.652–1.050)	0.730	< 0.001
FM (kg)	0.103	0.461	0.497	1.108 (0.824–1.491)	0.987	< 0.001
FM (%)	0.013	0.008	0.929	1.013 (0.767–1.336)	0.977	< 0.001
FM/LBM (ratio)	−0.005	0.001	0.976	0.995 (0.711–1.392)	0.986	< 0.001
WTI (WC/TG)	−0.227	5.256	0.022	0.797 (0.656–0.968)	0.803	< 0.001
CI (%,pg/ml, nmol/L)	−0.841	0.3178	0.049	0.451 (0.187–0.996)	0.742	< 0.001
BSI	−0.274	11.388	0.001	0.761 (0.649–0.892)	0.601	< 0.001
VAI	−0.999	4.204	0.040	0.369 (0.142–0.957)	0.726	< 0.001
LAP (cm, mmol/L)	−0.024	3.971	0.046	0.976 (0.954–1.000)	0.886	< 0.001
Go (mmol/L)	0.676	1.302	0.254	1.966 (0.616–6.282)	0.708	< 0.001
Io (pmol/L)	0.175	0.161	0.688	1.192 (0.506–2.084)	0.785	< 0.001
C-pep (nmol/L)	−0.138	1.815	0.178	0.871 (0.713–1.065)	0.832	< 0.001
HOMA-IR	0.065	0.017	0.897	1.067 (0.397–2.866)	0.774	< 0.001
HOMA %B	0.133	0.098	0.755	1.143 (0.495–2.638)	0.701	< 0.001
eAG (mmol/L)	−0.022	0.055	0.814	0.978 (0.812–1.178)	0.699	< 0.001
TC (mmol/L)	0.145	0.096	0.752	1.156 (0.461–2.898)	0.630	< 0.001
HDL-C (mmol/L)	0.442	1.094	0.296	1.556 (0.679–3.565)	0.688	< 0.001
LDL-C (mmol/L)	0.084	0.035	0.852	0.919 (0.378–2.233)	0.602	0.002
VLDL-C (mmol/L)	−0.074	0.492	0.483	0.928 (0.755–1.142)	0.698	< 0.001
TG (mmol/L)	−0.270	0.748	0.006	0.763 (0.629–0.926)	0.740	< 0.001
DM	−0.212	0.836	0.361	0.809 (0.513–1.278)	0.812	< 0.001
IG	0.175	2.265	0.132	1.192 (0.948–1498)	0.732	< 0.001

Variable	B	Wald	Sig	Exp B (Lower-Upper)	AUC	p-value
SBP (mmHg)	0.279	0.387	0.568	1.323 (0.508–3.441)	0.773	< 0.001
DBP (mmHg)	0.130	0.048	0.826	1.138 (0.357–3.627)	0.742	< 0.001
BW (kg)	0.058	0.009	0.924	1.060 (0.320–3.500)	0.947	< 0.001
WC (cm)	−0.146	0.954	0.329	0.864 (0.645–1.158)	0.957	< 0.001
WHR (ratio)	−0.195	1.779	0.182	0.823 (0.618–1.096)	0.722	< 0.001
FM (kg)	0.013	0.005	0.944	1.013 (0.709–1.447)	0.987	< 0.001
FM (%)	0.342	0.225	0.636	1.408 (0.342–5.792)	0.978	< 0.001
WTI (ratio)	−0.355	8.615	0.003	0.701 (0.553–0.889)	0.809	< 0.001
CI (%, pg/ml, nmol/L)	−0.227	4.406	0.036	0.797 (0.645–0.985)	0.739	< 0.001
BSI (ratio)	−0.252	3.988	0.046	0.777 (0.607–0.995)	0.888	< 0.001
VAI	−0.267	4.276	0.039	0.766 (0.594–0.986)	0.723	< 0.001
LAP (cm, mmol/L)	−0.275	4.624	0.032	0.760 (0.591–0.976)	0.888	< 0.001
Go (mmol/L)	−0.032	1.773	0.183	0.968 (0.923–1.015)	0.703	< 0.001
Io (pmol/L)	−0.014	0.016	0.898	0.987 (0.803–1.273)	0.783	< 0.001
HOMA-IR	−0.492	0.946	0.331	0.611 (0.227–1.648)	0.775	< 0.001
HOMA %B	0.387	0.800	0.371	1.472 (0.632–3.437)	0.694	< 0.001
C-pep (nmol/L)	−0.028	2.464	0.116	0.972 (0.938–1.007)	0.838	< 0.001
eAG (mmol/L)	−0.561	1.544	0.214	0.571 (0.235–1.303)	0.719	< 0.001
TC (mmol/L)	−0.216	4.168	0.033	0.766 (0.600–0.962)	0.652	< 0.001
HDL-C (mmol/L)	−0.046	0.204	0.652	0.955 (0.783–1.166)	0.689	< 0.001
VLDL-C (mmol/L)	−0.040	3.888	0.049	0.961 (0.923–1.000)	0.705	< 0.001
TG (mmol/L)	−0.738	7.629	0.006	0.720 (0.920–0.909)	0.740	< 0.001
LDL-C (mmol/L)	−0.115	1.007	0.316	0.891 (0.711–1.116)	0.611	< 0.001
DM	−0.091	2.495	0.114	0.913 (0.815–1.022)	0.849	< 0.001
IG	−0.059	0.010	0.918	0.943 (0.306–2.909)	0.735	< 0.001

Dependent variables	Retained independent variables	B	Wald	P	Exp B (Lower-Upper)	AUC	p-value
Non-PCOS
WHR (ratio)	DHEAS/T	−0.8113	5.857	0.016	0.444(0.230–0.857)	0.663	< 0.001
eAG (mmol/L)	DHEAS	−1.881	4.848	0.028	0.152(0.145–0.903)	0.704	0.001
NA-PCOS
BW (kg)	DHEA	0.979	4.360	0.037	2.662(1.062–6.672)	0.977	< 0.001
Go (mmol/L)	DHEA/T	0.957	5.498	0.019	2.605(1.170–5.800)	0.906	< 0.001
HOMA %B	DHEA	−0.543	4.277	0.039	0.581(0.348–0.972)	0.739	< 0.001
HA-PCOS
WTI (ratio)	DHEA/T	−0.350	8.263	0.004	0.705(0.555–0.895)	0.809	< 0.001
CI (%, pg/ml, nmol/L)	DHEAS/T	0.434	8.405	0.004	1.544(1.151–2.071)	0.759	< 0.001
VAI	DHEA	−0.299	7.511	0.006	0.741(0.599–1.136)	0.719	< 0.001
LAP (cm, mmol/L)	DHEA/T	−0.265	4.291	0.038	0.767(0.597–0.986)	0.888	< 0.001
TC (mmol/L)	DHEAS/T	−1.189	8.037	0.005	0.305(0.134–0.693)	0.666	< 0.001
TG (mmol/L)	DHEA	−0.300	9.380	0.002	0.741(0.611–0.897)	0.739	< 0.001

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[1] Address for correspondence
Sebastião Freitas de Medeiros, MD, PhD, Rua Quarenta e Nove, 2367, 78060-900, Boa Esperança, Cuiabá, MT, Brazil (e-mail: de.medeiros@terra.com.br).