Premature Pubarche: A Precursor of Future Health Issues?

MOLLY JARCHOW ND, LM

Premature pubarche (PP), the premature development of pubic hair, is a common presentation in pediatric practice and tends to affect many more girls than boys. PP is defined as pubic or axillary hair development in girls under the age of 8 and in boys under the age of 9. Pubarche is the physical manifestation of adrenarche, the awakening and development of the adrenal zona reticularis and subsequent increase in adrenal C19 steroid hormones. The C19 adrenal hormones include androstenedione, testosterone, and dehydroepiandrosterone sulfate (DHEAS), the latter of which is the primary marker of adrenarche. Peripherally, these adrenal androgens influence the growth of pubic and axillary hair as well as sebaceous and apocrine gland development. PP is different from precocious puberty, as it does not include breast bud or testicular development, and usually does not cause acceleration in linear growth velocity.¹ 

Differential Diagnosis 

PP is a diagnosis of exclusion once other conditions that increase adrenal steroid hormones have been ruled out. The main differentials for PP are precocious puberty, the virilizing form of classical congenital adrenal hyperplasia (CAH), and nonclassical CAH. Both forms of CAH are often linked to 21-hydroxylase deficiency.² Other less common causes of elevated adrenal androgens include androgen secreting tumors, Cushing’s syndrome, and rare genetic disorders. Once these conditions have been ruled out, PP is considered a variation of normal development.¹ 

Evaluation 

A bone age X-ray study of the left hand and wrist is the most important initial evaluation of PP. Depending on the presentation, progression, and bone age results, additional tests may be required. To rule out other causes of elevated adrenal androgens, other tests to consider include DHEAS, testosterone, androstenedione, and 17-hydroxyprogesterone, all drawn at 8 AM. A pediatric endocrinologist referral is warranted if the bone age is greater than or equal to 2 standard deviations above the child’s chronological age, if virilization is present, if symptoms are rapidly progressing, or if preliminary bloodwork shows elevated levels of adrenal androgens.¹ 

Associated Conditions 

Higher maternal body mass index (BMI) levels and gestational diabetes have been associated with PP in girls,³ suggesting that PP may be a marker of metabolic imbalance that started in the womb. Girls presenting with PP may or may not present with obesity or obvious insulin resistance at the time of onset.¹ Most of the girls I have seen in practice for PP have been of a healthy weight for their age. Although girls with PP usually do not progress to precocious puberty, they are at a higher risk for polycystic ovary syndrome (PCOS), metabolic syndrome, cardiovascular, and mental health issues from puberty onward.^1,5 Girls with PP have similar lipoprotein(a) levels as their peers before puberty but higher levels during puberty – independent of BMI, fasting glucose, and insulin levels. Elevated lipoprotien(a) levels have also been associated with higher DHEAS and free testosterone levels.⁴ Although not all girls with PP will develop PCOS, women in their early 20s with a history of PP can present with similar signs as women with PCOS, including insulin resistance markers, androstenedione levels, and ovarian mass.⁵ Women with PP may also exhibit similar anxiety, depression, and eating disorder symptoms as those with PCOS.⁵ 

The biological effects of adrenal androgen exposure and brain development before puberty is still being studied, but early exposure, as in PP, may contribute to mental health issues (even during childhood).⁶ In a 2018 study by Marakaki et al, pre-pubertal girls with PP self-reported higher depression and anxiety than boys with PP as well as peers who were not experiencing PP. These results were independent of morning and evening salivary cortisol levels.⁶ Interestingly, parental assessments of behavior were similar for all groups in the study, providing a striking insight that the anxiety and depression that PP girls experience may not be easily perceptible to parents.⁶ 

Case Study 

A mother brought her 7-year-old daughter in for a visit after noticing the development of pubic hair and body odor over the course of a few months. There was no family history of precocious puberty, PCOS, or diabetes, and her mom experienced menarche at age 14. Her father’s family history was significant for cardiovascular health issues. No one in the house used topical androgen products and the family ate a mostly organic diet. She was not taking any medications other than a daily vitamin D supplement. She experienced more stress in the prior year with the pandemic but had healthy outlets for stress and connection, including drawing, spending time with her animals, and virtual video playdates with friends. 

Physical exam revealed a well-appearing girl with a BMI of 16.5 and normal vitals. Her growth was linear and consistent for her height and weight. Fine, light-colored hair covered her mons pubis, and several coarse dark hairs lined her labia majora, consistent with Tanner Stage II of development. She had no clitoral enlargement. Her breast buds were Tanner Stage I, not palpable. Her thyroid was normal, she had no axillary hair and no acne, and her abdominal and neurological exams were normal. 

I ordered a bone age X-ray, and although her results came back normal, I ordered bloodwork to provide a baseline for fasting blood sugar, insulin, HbA1c, lipids, vitamin D, and DHEAS – all of which were normal. 

I informed her parents that between the bone age study, the labs, her consistent growth, and the slow progression of her symptoms, PP was the most likely diagnosis. However, I stated that we needed to monitor her every 6 months to make sure she wasn’t progressing rapidly or showing signs of puberty, which would prompt a reassessment and referral to a pediatric endocrinologist. We discussed proactive ways to support healthy metabolic and cardiovascular health, especially when she started puberty. These recommendations are the same for people of any age with these risk factors: regular physical activity, a whole-foods diet emphasizing colorful, high-fiber foods, and minimizing refined carbohydrates, sugars, and juices. We also discussed the importance of monitoring her for anxiety and depression, especially with pandemic-related stress and isolation. I recommended an omega-3 fish oil and magnesium glycinate for metabolic and mood support, especially during times of higher stress, and continuation of her vitamin D supplement. 

Although much research on endocrine disrupting chemicals has been focused on precocious puberty, we know these chemicals can cause complex interactions throughout the endocrine system. Relative to PP, these include androgen agonist and antagonist activity as well as obesogenic effects.⁷ For girls with PP who already have prematurely elevated androgens and are susceptible to insulin resistance, these chemicals may exacerbate their PP symptoms or may even be causative. To her parents, I recommended the Environmental Working Group’s website for resources to reduce chemical exposures, including their list for foods with the highest pesticides, their database to check personal care products, and their zipcode-based tool to check for water supply issues.⁸ 

Patients presenting with PP, especially girls, may provide foreshadowing of future hormonal, metabolic, cardiovascular, and mental health issues. By knowing the appropriate signs and symptoms, we can take the opportunity to properly evaluate and monitor patients. Additionally, we can educate families, screen for metabolic or hormonal imbalances, and begin treatment early to support both the physical and mental health of these patients as they move into puberty and beyond. 

References

1. Witchel SF, Rosenfeld RL. Premature adrenarche. Last updated June 16, 2021. UpToDate. Available at: https://www.uptodate.com/contents/premature-adrenarche. Accessed December 6, 2021. 

2. Oberfield SE, Sopher AB, Gerken AT. Approach to the girl with early onset of pubic hair. J Clin Endocrinol Metab. 2011;96(6):1610-1622. 

3. Kubo A, Ferrara A, Laurent CA, et al. Associations Between Maternal Pregravid Obesity and Gestational Diabetes and the Timing of Pubarche in Daughters. Am J Epidemiol. 2016;184(1):7-14. 

4. Andiran N, Yordam N. Lipoprotein(a) levels in girls with premature adrenarche. J Paediatr Child Health. 2008;44(3):138-142. 

5. Livadas S, Bothou C, Kanaka-Gantenbein C, et al. Unfavorable Hormonal and Psychologic Profile in Adult Women with a History of Premature Adrenarche and Pubarche, Compared to Women with Polycystic Ovary Syndrome. Horm Metab Res. 2020;52(3):179-185. 

6. Marakaki C, Pervanidou P, Papassotiriou I, et al. Increased symptoms of anxiety and depression in prepubertal girls, but not boys, with premature adrenarche: associations with serum DHEAS and daily salivary cortisol concentrations. Stress. 2018;21(6):564-568. 

7. Lucaccioni L, Trevisani V, Marrozzini L, et al. Endocrine-Disrupting Chemicals and Their Effects during Female Puberty: A Review of Current Evidence. Int J Mol Sci. 2020;21(6):2078. 

8. Environmental Working Group. Consumer Guides. EWG Web site. Available at: https://www.ewg.org/consumer-guides. Accessed December 15, 2021. 

Molly Jarchow, ND, LM, graduated from Bastyr University in Seattle, WA, where she completed the naturopathic medicine and midwifery programs. In 2014 she co-founded LA Midwife Collective and founded Sage Naturopathic Medicine. After welcoming over 400 babies into the world, Dr Molly retired from births and now focuses on women’s health and primary care pediatrics in her Santa Monica and Los Angeles offices. She’s an avid lover of herbs and whole foods, and she uses them regularly in her prescriptions. Outside of the office you can find Dr Molly cycling in the beautiful mountains of Southern California.