Health-Related Quality of Life of Young Adult Women with a History of Premature Adrenarche

Premature adrenarche (PA) refers to a clinical manifestation of adrenal androgen activity before the age of 8 years in girls or 9 years in boys [1]. These signs include comedones/acne, pubic/axillary hair, adult-type body odor, and greasiness of hair. Girls with PA also typically present with taller stature, increased weight and androgen levels, and earlier menarche compared to their peers [1]. Despite the considerably high prevalence of PA, its long-term consequences are still mostly unknown.

The most abundant adrenal androgens in PA, dehydroepiandrosterone, and its sulfate conjugate (jointly DHEA[S]) are neuroactive steroids with suggested diverse effects in the brain [2]. The proposed, usually beneficial neurodevelopmental effects of DHEA(S) during childhood and adolescence are, however, timing-sensitive, so that variation in the timing of such steroid action may lead to adverse developmental trajectories and adulthood outcomes [3, 4]. Earlier maturation relative to peers may also make this important transitioning phase especially challenging and confusing. Such added psychosocial stress could lead to unfavorable neuropsychological outcomes [5].

Such adversities would presumably impact how women with prior PA experience their health-related quality of life (HRQoL), but to our knowledge no such prior studies on adults exist. We have previously studied our PA cohort at the age of 12 years and found that the PA girls had comparable HRQoL compared to controls [6]. However, as the mechanisms described above are incremental in nature, more pronounced effects in HRQoL outcomes may emerge later at postpubertal age.

In this study, we continued to follow and investigate our PA cohort, now at young adult age, with the aim of assessing whether a history of PA influences self-assessed HRQoL in adulthood. In addition, we describe the relationship and living status of these young women as socioeconomic outcomes.

Originally, 73 children with PA (median 7.5 years; age range 4.8–9.9 years) and 99 healthy age-matched controls (median 7.6 years; age range 5.1–8.9 years) were recruited [6]. All PA children presented with at least one clinical sign of adrenal androgen action before age 8 in girls and 9 in boys, and other reasons for hyperandrogenism were excluded. Other exclusion criteria included long-term medication and any endocrinological disorder. All participants were invited to attend a follow-up visit at young adult age, and altogether 70 women participated (30 PA, 40 controls; median age 18.1 [range: 16.5–23.5] and 18.1 [range: 16.9–19.8] years, respectively). Too few men attended to yield meaningful results.

Height was measured with a calibrated stadiometer (Holtain Ltd., Crymych, UK), and weight with a calibrated scale. Both were recorded to the nearest 0.1 cm/kg. Standard deviation scores (SDSs) were calculated according to the latest Finnish growth references [7]. ISO-BMI was calculated from prepubertal BMI SDS, and it corresponds to BMI used in adults [7]. Overweight was classified as BMI or ISO-BMI >25, depending on subject’s age. Menarcheal age was obtained by interviewing, and information on relationship statuses and living arrangements with a questionnaire.

HRQoL was measured with a standardized 15D questionnaire [8]. 15D includes 15 dimensions: breathing, mental function, speech, vision, mobility, usual activities, vitality, hearing, eating, excretion, sleeping, distress, discomfort and symptoms, sexual activity, and depression. The respondents evaluated each dimension on five levels (1 = best, 5 = worst). These were then calculated into index scores for each dimension and the overall 15D score (1 = full health, 0 = being dead) by using a set of population-derived utility weights. The participants’ mean scores were also compared to a reference population means. This reference population (n = 43) includes 18–24-year-old women in a Finnish population sample [9].

All analyses were performed with the IBM Statistics SPSS software version 27.0 (IBM Corp., Armonk, NY, USA). Continuous variables are expressed as mean (SD) or median (interquartile range) and analyzed with the independent sample t test or Mann-Whitney U test depending on distributions. Categorical variables are expressed as n (%) and analyzed with the χ² test. One-way ANCOVA was used to assess the effect of confounding variables.

More extensive background information and other adulthood outcomes of this PA cohort from different perspectives are available from our previous publications [6, 10, 11]. The PA group had higher prepubertal height SDS and ISO-BMI, but the difference in the prevalence of childhood overweight did not reach statistical significance (Table 1). The differences in height and BMI had vanished by adult age (Table 1). The PA women reached menarche earlier than the controls (Table 1).

The overall 15D score was similar in both groups (PA, 0.956; control, 0.947; p = 0.482), and there were no differences on any of the dimensions (Fig. 1). When compared to the reference population, the PA women had better scores on the dimensions of mental function, depression, vitality, and sexual activity (Fig. 1). Compared to the reference population, the controls had lower scores on the dimensions of seeing and hearing, but higher scores on the dimensions of usual activities and sexual activity (Fig. 1).

Overweight study participants (n = 22, 31%), independent of PA, had similar overall 15D scores compared to normal weight participants (n = 48, 69%): 0.95 (0.90–0.99) versus 0.97 (0.95–1.00), p = 0.173, even after controlling for age at assessment and current illness (p = 0.099). There were no differences between the groups in relationship statuses or living arrangements (Table 1).

To our knowledge, no prior study has examined self-assessed HRQoL in adults with a history of PA. We have previously studied these same groups in adolescence and found that the overall 16D scores (15D modified for adolescents) were similar in both groups – as was the case in young adult age according to the present study. In adolescence, the PA group was worse off on the dimension of speech, possibly reflecting insecurity in social situations [6]. We did not detect this difference anymore at adult age, which may be due to improved self-confidence in the PA women.

In the previous study, we also found that being overweight, independently of PA, was associated with lower HRQoL in adolescence [6]. Overweight has been consistently shown to have a negative effect on HRQoL in adults [12]. In the present study, however, adult participants with overweight had similar HRQoL compared to those with normal weight. Adolescence may represent a psychosocially more challenging period for overweight individuals. However, these results may also be due to a relatively small sample size or attrition bias.

There were statistically significant, but in absolute terms marginal differences on some dimension scores between the groups in the study and the reference population. These differences are small, however, and not clinically relevant. Further, there were no statistically significant and/or clinically significant differences in the overall 15D scores between these groups.

Earlier menarche, as a proxy for earlier maturation, has been linked with increased prevalence of depression and other internalizing symptoms [5]. Contrary to these associations, our study showed that while PA women experienced menarche earlier than controls, they had comparable scores on all 15D dimensions.

In conclusion, this study suggests that PA is not a risk factor for worse self-assessed HRQoL at young adult age. Of note, earlier studies have shown that clinical signs of androgen action in PA girls tend to differ between different ethnic cohorts, and in some other cohorts, the long-term outcome has been different compared to our study [1]. Results of this study may not, therefore, be fully generalizable to other countries with different ethnic backgrounds.

Study protocol was reviewed and approved by the Research Ethics Committee of the Hospital District of Northern Savo, approval number 23/2013. Written informed consents were received from the participants’ parents when the participants were under the age of 18 years and from the participants themselves at adult age, both according to the Declaration of Helsinki.

Harri Sintonen is the developer of the 15D and obtains royalties from its electronic versions. The other authors have no conflicts of interest to declare.

This work was supported by Kuopio University Hospital (Kuopio, Finland), University of Eastern Finland (Kuopio, Finland), the Foundation for Pediatric Research (Helsinki, Finland), the Finnish Medical Foundation (Helsinki, Finland), the Päivikki and Sakari Sohlberg Foundation (Helsinki, Finland), the Sigrid Jusélius Foundation (Helsinki, Finland), and the Emil Aaltonen Foundation (Tampere, Finland). The funders had no role in (1) study design; (2) the collection, analysis, and interpretation of data; (3) writing of the report; or (4) the decision to submit the paper for publication.

P.U., J.L., J.J., and R.V. designed and prepared the study; P.U. and J.L. prepared and carried out the clinical research visits; P.U., J.L., and J.J. created and constructed the database; H.S. designed the questionnaire used and analyzed the results. J.T., J.L., and J.J. performed statistical approaches and analyses; J.T. wrote the manuscript; J.J., P.U., R.V., H.S., and J.L. performed critical review of the manuscript; all authors read and approved the final manuscript.

The data that support the findings of this study are not publicly available due to their containing information that could compromise the privacy of research participants but are available from the corresponding author [J.T.] upon reasonable request.