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Abstract

Background:

Polycystic ovarian syndrome (PCOS) develops from early puberty on and progresses afterward, and a persistent hyperandrogenic state puts adult PCOS patients at risk of metabolic abnormality. If hyperandrogenism-related metabolic problems can be detected early in adolescence, it could have a quite positive impact on patients’ reproductive health and cardiovascular disease prevention in the future. Accordingly, this study was performed to delineate the clinical and biochemical hyperandrogenic status of adolescents with irregular menses, and to explore which one was more noteworthy in this population.

Method:

Based on the questionnaire of an epidemiological survey carried out by our research team, this case–control study compared the anthropomorphic, clinical, and laboratory materials of adolescent girls, at least 2 years after menarche, with irregular menses, as well as those with regular periods. Androgen and metabolism-related indicators were measured in their serum samples. Simultaneously, they were categorized and compared based on whether they presented with hirsutism (mFG ≥6).

Results:

There were no significant differences in serum androgen parameters between the hirsute and nonhirsute groups. The mFG score was found to be slightly positively correlated with A2 and dehydroepiandrosterone sulfate (DHEAS), and there was no significant correlation with other clinical and androgenic indicators. There were no significant differences in various clinical indicators, serum androgens, or the incidence of hirsutism between girls with oligo-/amenorrhea and girls with normal menses. When compared to girls with normal menses, those with oligo-/amenorrhea were more likely to have a higher risk of developing biochemical hyperandrogenism [odds ratio (OR) = 1.961 (1.131–3.401), p = 0.021], and had a similar prevalence of hirsutism [OR = 0.651(0.314–1.352), p = 0.294]. Body mass index (BMI), waist circumference, waist–hip ratio, diastolic blood pressure, fast insulin (FIN), triglyceride (TG), cholesterol (CHOL), and low density lipoprotein (LDL) of PCOS group and hyperandrogenism-only group were slightly higher than those of the control group. Within the PCOS group, the BMI, systolic blood pressure (SBP), FIN, TG, and CHOL of patients with biochemical hyperandrogenism were slightly higher than those in clinical hyperandrogenism. The incidence of hyperinsulinemia, overweight, or obesity in the PCOS group was significantly higher than that in the control group (p < 0.05), and there was no significant difference in the incidence of different types of hyperlipidemia, central obesity, or elevated blood pressure between the two groups (p > 0.05).

Conclusion:

At least 2 years after menarche, adolescent girls with oligo-/amenorrhea are more likely to have concomitant biochemical hyperandrogenism than those with hirsutism. In this population, those with hirsutism or hyperandrogenemia present a higher incidence of some metabolic abnormalities, such as hyperinsulinemia and being overweight or obese.

Introduction

Adolescence is a transitional stage during which the gonads are initiated by increased activity in the hypothalamus, leading to increased activity in the hypothalamic–pituitary–gonadal axis, which develops until maturity, and is often accompanied by hyperandrogenism and anovulation. Clinically, adolescent girls may experience acne, anovulatory menses, multicystic ovaries, and hyperinsulinemia to varying degrees.¹ These physiological events are usually temporary and do not cause health problems. However, if the anovulatory period of a girl lasts for more than 2 years after menarche, it cannot be simply interpreted as gonads immaturity, especially when accompanied by hyperandrogenism manifestations.^2,3 Therefore, it is necessary to identify polycystic ovary syndrome (PCOS), which has been reported to originate in early puberty.⁴

Androgens are a group of hormones that play a role in masculinity and reproductive activity and are present in both males and females. Moderate production of androgens has been proven to be essential for estrogen synthesis, pubertal sexual hair growth, bone loss prevention, as well as sexual desire and satisfaction. Androgen excess, namely hyperandrogenism, defined as clinical and/or biochemical features of increased androgen production and/or action, may manifest clinically as hirsutism, acne, alopecia, oily skin, oligo- or amenorrhea, or frank virilization.⁵ Although the diagnostic criteria for PCOS, the most common female reproductive endocrine disorder, have undergone some changes from the 1990 NIH criteria and the 2003 Rotterdam criteria to the 2006 Androgen Excess Society criteria, hyperandrogenism remains a mandatory evaluation parameter for diagnosis in any criteria.^6–8

In addition, the 2018 and 2023 International evidence-based PCOS guidelines, which are both based on the consensus of the 2003 Rotterdam criteria, confirm hyperandrogenism as an essential prerequisite for diagnosing PCOS.^9,10 However, due to the overlap between normal pubertal events and pathophysiological traits of PCOS, the diagnostic criteria for PCOS used in adults are inapplicable to the adolescent population.¹¹ Additionally, the discrepancy between clinical and biochemical hyperandrogenism presents in adolescents as well.¹²

PCOS develops during early puberty and progresses thereafter. Considering that persistent hyperandrogenic state predisposes PCOS patients to metabolic abnormalities, if hyperandrogenism-related metabolic problems can be detected early in adolescence, it could have a quite positive impact on the reproductive health and future prevention of cardiovascular disease in patients.^13–16 Therefore, based on an epidemiological survey carried out by our research team, this study aimed to describe the clinical and biochemical hyperandrogenic status of adolescents with irregular menses, and to explore which status was more noteworthy for this population.

Materials and Methods

Subjects

From January 2012 to April 2014, a cross-sectional epidemiological survey was conducted by our research team, and 1095 adolescent schoolgirls (14–18 years of age) were recruited eventually with written informed consent from the participants and their parents, with the permission of Institutional Review Board of Memorial Hospital of Sun Yat-sen University (Ref.2012005).¹⁷ The research population of this current study was entirely based on the abovementioned survey.

Questionnaire survey

Participants were asked to complete an epidemic questionnaire including menstrual conditions (menarche age, appearance of regular menstruation after menarche, menstrual cycle days, menstrual period, menstrual volume, dysmenorrhea, etc.).

Clinical measurements

They underwent anthropometric parameters measurements. The average of two measurements of blood pressure (BP) with the subject in the sitting position was taken at 5-minute intervals after resting for at least 15 minute. Height and weight were measured in light clothing without shoes, using a digital electronic scale. Body mass index (BMI) was calculated as the weight in kilograms divided by the square of height in meters. Waist and hip circumferences were measured at the narrowest and widest parts of umbilicus and buttocks respectively, and then the waist–hip ratio (WHR) was calculated. The presence of hirsutism was scored in every girl by the same investigator, using a modification of the Ferriman–Gallwey method, according to a given diagram.¹⁸ Thyroid and breast examinations were performed by palpation.

Biochemical and hormonal analysis

Plasma free-testosterone (fT), sex hormone binding globulin (SHBG), androstenedione (A2), dehydroepiandrosterone sulfate (DHEAS), and 17-hydroxyprogesterone (17-OHP) levels were measured by enzyme-linked immunosorbent assay (ELISA). Testosterone (T), prolactin (PRL), and thyroid stimulating hormone(TSH) levels were measured by chemiluminescence. The free androgen index (FAI) was calculated using the formula [serum testosterone (nmol/L)×100/SHBG (nmol/L)]. Fasting venous blood samples were also used to measure insulin, hypercholesterolemia (TC), triglyceride (TG), low density lipoprotein (LDL), and high density lipoprotein (HDL) levels. Plasma insulin was measured using a chemiluminescence immunometric assay and commercial kit (Immulite 2000 Analyzer: CPC). TC, HDL, and TG levels were measured using an enzymatic calorimetric method with a 7600 autoanalyser (Hitachi 7600). The LDL cholesterol levels were calculated using the Friedewald equation.

Diagnostic criteria

The diagnostic criteria of all the metabolism-related parameters below can be referred to the published studies performed by our research team. 1.

Hyperandrogenemia: The androgen indices detected in this study were T, A2, and FAI. Either of T, A2, and FAI elevated the below level. Namely, T ≥2.28 nmol/L, A2≥5.20 nmol/L, FAI ≥4.37, respectively.¹⁷

Hirsutism: F-G Score ≥6.¹⁷

The presence of PCOS was defined as: (1) oligo/anovulation(≤8 cycles per year, or menstrual cycle <21 days or >35 days in length, without taking hormonal contraception); (2) evidence of clinical hyperandrogenism (hirsutism, or acne or androgenic alopecia) and/or hyperandrogenemia; and (3) for those girls suspected of PCOS, serum TSH, PRL, 17-OHP were subsequently measured to rule out thyroid diseases (TSH outside the reference range [0.35–5.5 mIU/L]), hyperprolactinemia (PRL >24 μg/L), and congenital adrenal hyperplasia (17-OHP >6 nmol/L).¹⁷

Hyperinsulinemia: Fasting insulin ≥13.25 μU/mL

Hyperlipidemia: Either of TC ≥6.0 mmol/L, TG ≥1.7 mmol/L, LDL ≥3.6 mmol/L, and HDL ≤1.29 mmol/L.¹⁹

Central obesity: Waist circumference (WC) ≥80 cm, or WHR ≥0.85.²⁰

Overweight: BMI ≥23 kg/m².¹⁹

Obesity: BMI ≥25 kg/m².¹⁹

Acquisition of the research and control groups for analysis from different perspectives were recruited from our previously published survey study. 1.

To evaluate the relationship between hirsutism and different androgen parameters, 38 girls with hirsutism (F-G score ≥6) and 382 randomly selected girls without hirsutism were included in the analysis.

To evaluate the relationship between menstrual status and clinical and biochemical hyperandrogenism, 158 adolescent girls, at least 2 years after menarche, with oligo-/amenorrhea, as well as randomly selected 262 girls with regular periods were analyzed.

To evaluate the metabolism-related parameters and metabolic abnormality incidence among girls with different menstrual statuses and different hyperandrogenism types, 39 girls diagnosed with PCOS according to NIH criteria, 51 girls with regular menses and either hirsutism or hyperandrenemia, and 74 girls with regular menses and no sign of hyperandrogenism were compared.

Statistical analysis

Data were analyzed using the Statistical Package for Social Sciences software (version 13.0, SPSS Inc.). The Kolmogorov–Smirnoff normality test was used to test the distribution of continuous variables. If it conformed to a normal distribution, it was statistically described as the mean ± standard deviation. If the distribution was skewed, it was expressed as the median (upper quartile– lower quartile). The independent t-test and analysis of variance (ANOVA) were used to compare parametric data. Nonparametric data and categorical data are presented as frequencies (percentages). The Kruskal–Wallis and Mann–Whitney U tests were used to compare nonparametric data. The chi-square test was used to compare categorical data. Pearson’s Correlation test was used to determine correlations between continuous variables. Differences were considered statistically significant at p < 0.05.

Results

Various clinical and biochemical indexes among hirsute and nonhirsute girls

When comparing clinical and biochemical indices among hirsute and nonhirsute girls, we tried to display the difference in various androgen parameters between the two groups. As shown in Table 1, the levels of T, A2, and DHEAS, and the prevalence of hyperandrogenemia in the hirsute group were higher than those in the nonhirsute group, but the difference was not significant; The levels of FAI and fT were lower in the hirsute group, and there were no significant differences, either. In addition, Pearson’s univariate correlation analysis was conducted between the mFG score and various serum androgens and clinical indicators. The mFG score was found to be positively correlated with A2 and DHEAS, but the correlation coefficient was not high. There was no significant correlation between T, FAI, fT, age, menarche age, years after menarche, BMI, and WHR (detailed in Table 2).

Table 1.

Comparison of Clinical and Biochemical Indexes Between Hirsutism Group and Nonhirsutism Group

	Hirsutism group (n = 38)	Nonhirsutism group (n = 382)	p
Menarche age (years)	12.76 ± 1.03	12.51 ± 0.94	NS
BMI（kg/m²）	19.89 ± 2.67	20.34 ± 6.24	NS
WHR	0.76 ± 0.06	0.75 ± 0.06	NS
FAI	2.14 (1.22–2.87)	2.31 (1.25–2.77)	NS
T (nmol/L)	1.42 (0.86–1.78)	1.30 (0.88–1.63)	NS
A2 (nmol/L)	3.12 (1.88–4.14)	2.66 (1.56–3.50)	NS
fT (nmol/L)	1.88 (0.99–2.82)	2.07 (0.81–2.59)	NS
DHEAS (nmol/L)	1586.00 (981.50–2150.75)	1453.37 (929.00–1866.50)	NS
SHBG (nmol/L)	70.83 (59.62–81.43)	68.81 (53.11–78.99)	NS
Prevalence of hyperandrogenemia	18.4% (7/38)	14.9% (57/382)	NS

BMI, body mass index; DHEAS, dehydroepiandrosterone sulfate; FAI, free androgen index; NS, nonsignificance; SHBG, sex hormone binding globulin; WHR, waist–hip ratio.

Table 2.

Correlation Analysis of mFG Score with Various Serum Androgens and Clinical Parameters

Parameter	r	p
Age	0.012	0.803
Menarche age	0.037	0.454
Years after menarche	−0.028	0.570
BMI	0.034	0.487
WHR	0.078	0.110
FAI	−0.017	0.732
T	0.052	0.285
A2	0.111	0.022 ^*
fT	−0.013	0.790
DHEAS	0.096	0.049 ^*
SHBG	0.030	0.538

Bold values represent statistical significance.

p < 0.05.

BMI, body mass index; DHEAS, dehydroepiandrosterone sulfate; FAI, free androgen index; NS, nonsignificance; SHBG, sex hormone binding globulin; WHR, waist–hip ratio.

The relationship between menstrual status and clinical and biochemical hyperandrogenism

There were no significant differences in various clinical indicators, serum androgens, or the incidence of hirsutism between girls with oligo-/amenorrhea and girls with normal menses (Table 3). When compared to girls with normal menses, those with oligo-/amenorrhea were more likely to have biochemical hyperandrogenism [odds ratio (OR) = 1.961 (1.131–3.401), p = 0.021], and had a similar prevalence of hirsutism [OR = 0.651 (0.314–1.352), p = 0.294], as shown in Table 4.

Table 3.

Comparison of Clinical Parameters, Serum Androgens, and Incidence of Hirsutism Between Girls with Oligo/Amenorrhea and Normal Menses

	Oligo/amenorrhea group	Normal menses group
	(n = 158)	(n = 262)	^a p
Menarche age (years)	12.54 ± 0.95	12.52 ± 0.96	NS
BMI（kg/m²）	19.89 ± 2.92	20.55 ± 7.27	NS
WHR	0.75 ± 0.05	0.75 ± 0.06	NS
FAI	2.24 (1.20–2.81)	2.33 (1.28–2.72)	NS
T (nmol/L)	1.32 (0.88–1.67)	1.31 (0.89–1.62)	NS
A2 (nmol/L)	2.82 (1.61–3.69)	2.63 (1.53–3.44)	NS
DHEAS (nmol/L)	1406.73 (911.50–1765.50)	1501.10 (943.75–1942.00)	NS
SHBG (nmol/L)	75.14 (54.20–83.79)	65.25 (53.06–77.56)	NS
Incidence of hirsutism	7.6% (12/158)	9.5% (25/262)	NS

^ap for the difference was calculated based on the student t test for continuous variables and chi-squared test for categorical variables.

BMI, body mass index; DHEAS, dehydroepiandrosterone sulfate; FAI, free androgen index; NS, nonsignificance; SHBG, sex hormone binding globulin; WHR, waist–hip ratio.

Table 4.

OR Value of Risk Associated with Developing Biochemical Hyperandrogenism and Hirsutism Among Girls with Oligo-/Amenorrhea

	Normal menses	Oligo/amenorrhea
	n	n	OR (95% CI)	χ²	p value
BH	29	31
Non-BH	233	127	1.961 (1.131–3.401)	5.886	0.021

Hirsutism	27	11
Non-hirsutism	235	147	0.651 (0.314–1.352)	1.339	0.294

Bold values represent statistical significance.

BH, biochemical hyperandrogenism; CI, confidence interval; OR, odds ratio.

Comparison of metabolism-related parameters among PCOS group, hyperandrogenism-only group, and control group

In our previous survey,¹⁷ 31 girls with biochemical hyperandrogenism and 8 hirsute girls were diagnosed with PCOS. There were 51 girls in the hyperandrogenism-only group who had regular menses along with biochemical hyperandrogenism and/or hirstutism. Additionally, for the analysis in this section, 74 girls with regular menses and without hyperandrogenism were randomly selected as the control group.

As shown in Table 5, the BMI, WC, WHR, DBP, FIN, TG, CHOL, and LDL of PCOS group and hyperandrogenism-only group were slightly higher than those of Control group, but there was no significant statistical significance (p > 0.05); within the PCOS group, the BMI, SBP, FIN, TG, and CHOL of patients in biochemical hyperandrogenism were slightly higher than those in clinical hyperandrogenism, and the difference was not statistically significant.

Table 5.

Comparison of Metabolism-Related Parameters Among PCOS Group, Hyperandrogenism-Only Group and the Control Group

	PCOS group		Hyperandrogenism-only group	Control group
	BH group (n = 31)	CH group (n = 8)	(n = 51)	(n = 74)	p ^{a b}
Age（years）	15.68 ± 0.70	15.75 ± 0.46	15.70 ± 0.65	15.73 ± 0.63	NS
BMI（kg/m²）	21.51 ± 3.77	20.79 ± 2.77	21.22 ± 2.67	20.57 ± 7.96	NS
WC（cm）	68.29 ± 8.79	68.88 ± 7.90	68.41 ± 8.52	66.02 ± 6.54	NS
WHR	0.77 ± 0.05	0.77 ± 0.10	0.77 ± 0.06	0.75 ± 0.06	NS
SBP（mmHg）	110.94 ± 8.32	103.86 ± 3.89	108.60 ± 11.09	109.35 ± 9.54	NS
DBP（mmHg）	67.42 ± 7.47	69.14 ± 4.74	66.02 ± 7.43	66.87 ± 8.00	NS
FIN（μU/mL）	11.80 ± 11.77	10.60 ± 9.06	10.68 ± 10.39	8.55 ± 7.06	NS
TG（mmol/L）	1.25 ± 0.33	1.08 ± 0.35	1.23 ± 0.48	1.19 ± 0.42	NS
CHOL（mmol/L）	4.26 ± 0.79	3.68 ± 0.67	4.08 ± 0.86	3.95 ± 0.86	NS
HDL（mmol/L）	1.62 ± 0.32	1.61 ± 0.24	1.53 ± 0.30	1.62 ± 0.31	NS
LDL（mmol/L）	2.34 ± 0.59	2.41 ± 0.37	2.43 ± 0.71	2.20 ± 0.65	NS

p^a, comparsion among PCOS group, hyperandrogenism-only group, and control group.

p^b, comparsion between BH group and CH group.

BH, biochemical hyperandrogenism; BMI, body mass index; CH, clinical hyperandrogenism; CHOL, cholesterol; DBS, diastolic blood pressure; FIN, fast insulin; LDL, low density lipoprotein; NS, nonsiginificance; PCOS, polycystic ovarian syndrome; SBP, systolic blood pressure; TG, triglyceride; WHR, waist–hip ratio.

Comparison of the incidence of various metabolic abnormalities between PCOS group and control group

Taking the 75th percentile of the overall test population as the threshold for the diagnosis of Hyperinsulinemia, that is, FIN ≥13.25 μG/mL. The incidence of hyperinsulinemia, overweight, or obesity in the PCOS group was significantly higher than that in the control group (p < 0.05), and there was no significant difference in the incidence of different types of hyperlipidemia, central obesity, or elevated blood pressure between the two groups (p > 0.05). See details in Table 6.

Table 6.

Comparison of the Incidence of Various Metabolic Abnormalities Between PCOS Group and Control Group

	PCOS group	Control group
	[%(n/N)]	[%(n/N)]
Hyperinsulinemia	41.0 (16/39)	20.3 (14/74)^a
Hyperlipidemia	15.4 (6/39)	13.5 (10/74)
Hypercholesterolemia	2.6 (1/39)	1.4 (1/74)
Hypertriglyceridemia	10.3 (4/39)	9.5 (7/74)
Elevated LDL	5.1 (2/39)	5.4 (4/74)
Reduced HDL	2.6 (1/39)	4.1 (3/74)
Central obesity	10.3 (4/39)	4.1 (3/74)
Overweight or Obesity	25.6 (10/39)	9.5 (7/74)^a
Elevated SBP and/or DBP	0 (0/39)	0 (0/74)

Bold values represent statistical significance.

Chi-square test, p < 0.05.

DBP, diastolic blood pressure; HDL, high-density lipoprotein; LDL, low-density lipoprotein; PCOS, polycystic ovarian syndrome; SBP, systolic blood pressure.

Discussion

In the first few years after menarche, due to anovulation, menses may manifest as oligo/amenorrhea. As age increases, the menstrual cycle usually becomes shorter and more regular. Therefore, oligo/amenorrhea, previously regarded as an inevitable stage in the physiological process of HPO axis maturation, has been widely overlooked by both parents and practitioners.^21,22 In fact, after menarche, 55–82% of adolescent girls develop a regular ovulation period within 2 years, and only 22% maintain anovulatory or oligo-ovulatory cycles after 2 years, whereas only a few girls need up to five years to establish a regular ovulation cycle.²³ In our previous survey, with an increase in age after menarche, the incidence of oligo/amenorrhea among girls who were over 2 years after menarche was significantly lower than that of those within 2 years after menarche. In addition, even in the first 2 years after menarche, the incidence of menstrual cycle >90 days was less than 5%, indicating that even in adolescent girls, menstrual cycles exceeding 3 months cannot be reasonably explained solely by immature reproductive axis development, and the possibility of pathological factors, such as PCOS, should not be ignored.¹⁷ Accordingly, the guideline recommends screening for adolescent PCOS in girls who still have irregular menses 2 years after menarche.⁹

During adolescence, in addition to physiological anovulation, physiological hyperandrogenism is also relatively common, characterized by slight hair growth on the upper lip and side face, which may extend to the lower jaw and neck, and may also be accompanied by abdominal hair growth. These hairs are usually lighter in color and thinner in diameter, which is a physiological manifestation of adrenarche.^24,25 However, if androgens sustain their effect on the body, these hairs will gradually turn dark and dense, even appearing in the area between the umbilicus and pubes, upper abdomen, and chest, showing a male distribution. Therefore, it should be clarified that hair growth or mild hirsutism in the upper lip area of adolescent girls does not necessarily indicate androgen excess, but if hair growth persists and gradually worsens, high vigilance should be exercised for potential androgen excess and PCOS.²⁶

The most commonly used scoring system for evaluating clinical hyperandrogenism is the modified Ferriman–Gallwey (mFG) scale adapted by Hatch et al.²⁷ Although this indicator is considered subjective and has inter-observer and inter-ethnic differences,²⁸ a systematic retrospective analysis fully confirmed the role of mFG in diagnosing PCOS and evaluating the clinical manifestations of hyperandrogenism.¹⁸ In this study, an mFG >6 was adopted as the clinical standard for hyperandrogenism. Girls with hirsutism had similar levels of T, A2, DHEAS, FAI, and fT to those without hirsutism; Moreover, Pearson univariate correlation analysis was conducted between mFG score and various serum androgen levels and clinical indicators. The results showed that the mFG score was positively correlated with A2 and DHEAS, while the correlation coefficient was not high.

There was no significant correlation between T, FAI, fT, age, age at menarche, years after menarche, BMI, and WHR, indicating that there was no high correlation between clinical and biochemical hyperandrogenism in the adolescent population, which is consistent with reports from all other researchers.²⁹ However, our results indicated that compared to girls with normal menses, those with oligo-/amenorrhea had a higher chance of biochemical hyperandrogenism [OR = 1.961, p = 0.021], and had a similar prevalence of hirsutism [OR = 0.651, p = 0.294], which is consistent with the study by Celik et al.,³⁰ suggesting that girls with irregular menstruation, even without hirsutism, still need to be alert to hyperandrogenemia.

According to current diagnostic criteria, girls with oligo-/amenorrhea and any clinical and biochemical hyperandrogenism will be considered as having suspected adolescent PCOS.⁹ PCOS is not only a reproductive endocrine disease but also has a much higher incidence of metabolic abnormalities than the normal population.³¹ Their metabolic characteristics (obesity, insulin resistance, abnormal lipid metabolism, etc.) increase the risk of cardiovascular disease in this population. Traditionally, metabolic syndrome (MS) was thought to occur only in adults; however in the past decade, an increasing number of researchers have noticed that MS also occurs in children and adolescents.^32,33 Due to the lack of blood glucose data in this study, the incidence of MS in adolescent PCOS patients could not be obtained, and the sample size of the detected adolescent PCOS was not large enough. However, it can still be seen that the incidence of metabolic abnormalities related to MS (hyperinsulinemia, overweight, or obesity) in adolescent PCOS is significantly higher than that in the control group; Compared with the control group of girls, the clinical and metabolic indicators (including BP, FIN, CHOL, TG, and LDL) of adolescent PCOS and girls with pure hyperandrogenism of the same age showed an upward trend. Although there were no statistical differences between the above groups, we considered this to be related to the small sample size, younger age, and short disease duration of the patients. Our research group also observed the occurrence of MS in adolescent PCOS patients from clinics in the early stages,¹⁹ and the relevant data were slightly higher than the results of this survey. We believe that this may be related to the more obvious general clinical symptoms of the patients who visited the clinic for treatment. In addition, previous studies have confused clinical hyperandrogenism with biochemical hyperandrogenism. When distinguishing them, Fruzzetti found that at least during adolescence, PCOS patients with biochemical hyperandrogenism were more likely to experience lipid metabolism abnormalities than those with only clinical hyperandrogenism.³⁴ Our study also indicated that compared to PCOS patients with only clinical hyperandrogenism, those with biochemical hyperandrogenism showed an increasing trend in multiple metabolic indicators (BMI, SBP, FIN, TG, and CHOL). Although there was no statistically significant difference, this could be related to the small sample size. Expanding the sample size in the future may elucidate the relationship between biochemical hyperandrogenism and metabolic abnormalities in adolescent PCOS patients.

Limitation

The present study also has certain limitations. All the materials and data adopted for analysis in this study were obtained from an epidemiological survey carried out by our research team. The survey participants were adolescent girls from randomly selected high schools. Therefore, the number of girls with hirsutism or hyperandrogenemia in this school-based study was relatively small when compared with that in clinic-based studies. Moreover, in this study, the androgen parameters were measured by ELISA or chemiluminescence, which are not the optimal methods stated in the latest guidelines. In addition, even though PCOS develops during adolescence, the comparatively short course is not enough for the girls to present with obvious metabolic abnormalities.

Conclusion

This case–control study revealed that at least 2 years after menarche, adolescent girls with oligo-/amenorrhea are more likely to have concomitant biochemical hyperandrogenism than those with hirsutism. In this population, those with hirsutism or hyperandrogenemia present a higher incidence of some metabolic abnormalities, such as hyperinsulinemia and being overweight or obese. Further clarification is required to expand the sample size.

Footnotes

Authors’ Contributions

Y.H. and D.Y.: Responsible for the concept and design of this study; Y.H., Z.Z., and Z.D.: In charge of acquisition of data; Y.H. and D.Y.: Analyzed the data; Y.H. and L.H.: Drafted the article; Y.H. and D.Y.: Critically revised the important intellectual content. All the authors conform to the International Committee of Medical Journal Editors (ICMJE) criteria for authorship, contributed to the intellectual content of the study, reviewed the article, and approved the final version of the article. The authors alone are responsible for the content and writing of the article.

Author Disclosure Statement

The authors declare no conflicts of interest.

Funding Information

This study was financially supported by The 5010 grants of Sun Yat-Sen University (SYSU2014005) in China, and the Science and Technology Development Fund (FDCT 0003/2022/A and 0001/2024/RIA1) of Macau Special Administrative Region.

Abbreviations Used

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Hirsutism or Hyperandrogenemia,Which is More Noteworthy for Adolescent Girls with Irregular Menses? A Case–Control Study Based on an Epidemiological Survey

Abstract

Background:

Method:

Results:

Conclusion:

Introduction

Materials and Methods

Subjects

Questionnaire survey

Clinical measurements

Biochemical and hormonal analysis

Diagnostic criteria

Statistical analysis

Results

Various clinical and biochemical indexes among hirsute and nonhirsute girls

The relationship between menstrual status and clinical and biochemical hyperandrogenism

Comparison of metabolism-related parameters among PCOS group, hyperandrogenism-only group, and control group

Comparison of the incidence of various metabolic abnormalities between PCOS group and control group

Discussion

Limitation

Conclusion

Footnotes

Authors’ Contributions

Author Disclosure Statement

Funding Information

Abbreviations Used

References