Which of the following characteristics is typically associated with being an early-maturing girl?

Precocious Puberty

Precocious puberty in girls is defined as the onset of thelarche prior to 8 years of age, or menarche before 9 years of age. For boys, precocious puberty refers to genital development before 9 years of age. A brain imaging study of boys with familial precocious puberty revealed that these children responded faster to emotional stimuli and also exhibited different patterns of hippocampal activity during emotional processing compared with controls. However, sexual behavior was not measured.

Early maturing girls are more likely to report problems with body image and also increased sexual activity compared with later maturing girls. Perhaps related to dissatisfaction with their body image, early maturing girls (but not boys) are also more likely to report social anxiety than are children who experience typical timing of pubertal onset (Blumenthal et al., 2011). On the other hand, early maturing boys are more likely to report increased sexual activity and illicit substance use (Ehrhardt & Meyer-Bahlburg, 1994; Michaud, Suris, & Deppen, 2006).

More recently, two follow-up studies were conducted to investigate if behavioral correlates of early reproductive development in girls (e.g., mental distress, increased sexual activity) persist into adolescence and early adulthood. In the first study, girls with early menarche initially reported elevated mental distress and increased number of sexual partners. However, an elevated level of mental distress and increased number of sexual partners did not persist over the 3-year follow-up period (Lien, Haavet, & Dalgard, 2010). Similar results were found in a second study, where young girls with early breast development and/or menarche exhibited increased use of illicit substances, earlier age at first intercourse, and poorer psychiatric functioning initially, but these behaviors reportedly ameliorated by 19–21 years of age (Copeland et al., 2010). Thus, while precocious or early puberty are related to earlier timing of first intercourse and greater number of sex partners, these differences appear to dissipate by the late teenage years.

Ovulation and Menarche

Positive feedback of estrogen on the hypothalamic–pituitary axis is a late development during puberty and is the phenomenon that allows ovulation and menarche. Menarche usually follows thelarche by 2.5–3 years. After midpuberty, estrogen in the appropriate amount at the appropriate time can stimulate gonadotropin release, whereas higher doses of estrogen will still suppress gonadotropin secretion. The ratio of LH to FSH secretion rises as the frequency of pulsatile GnRH release increases during the late follicular phase of the normal menstrual cycle. Increased LH secretion stimulates estrogen production from the ovary which through positive feedback leads to the midcycle LH surge that causes ovulation. As discussed above, administration of GnRH in pulsatile fashion by a programmable pump is utilized to allow fertility in patients with hypogonadotropic hypogonadism or hypothalamic GnRH deficiency as this pump can mimic the natural pattern of gonadotropin secretion and trigger ovulation.

However, even if the midcycle surge of gonadotropins is present, ovulation may not occur during the first menstrual cycles after menarche as 90% of menstrual cycles are anovulatory in the first year after menarche. By 5 years after menarche, about 80% of periods are ovulatory. The high prevalence of anovulatory periods during this period, however, may be less due to development than unrecognized polycystic ovary syndrome. However, it is always important to realize that some of the first cycles after menarche may be ovulatory, and fertility is possible in the first cycle.

Secular trends and racial and ethnic differences in the onset and tempo of puberty

Reports of secular changes in the onset of puberty have focused on girls and have typically used age at menarche as the biomarker for puberty. During medieval times, undernutrition, increased infections, and greater physical exertion likely contributed to later onset of puberty (Arthur et al., 2016; Lewis et al., 2016). Beginning in the early 19th century to the latter half of the 20th century, the age at menarche declined in Europe and North America from approximately 16–17 to 13 years of age. This trend has been attributed to the improving socioeconomic conditions during this time.

In both North America and Europe, breast and pubic hair development are now occurring earlier than 50 years ago (Biro et al., 2018). This earlier onset of breast development is not associated with increased gonadotropin or estradiol concentrations, suggesting that this represents a gonadotropin-independent event (Sørensen et al., 2012; Cabrera et al., 2014). Earlier breast development assessed by palpation was reported in non-Hispanic white girls, which was likely related to the increased body mass index (BMI) of this group (Biro et al., 2013). A systematic review and meta-analysis of clinical studies examining thelarche concluded that the age of thelarche has declined by almost 3 months per decade from 1977 to 2013 (Eckert-Lind et al., 2020).

Data from North America, several European countries, and other regions of the industrialized world suggest that the trend to earlier menarche has been reduced or halted (Sørensen et al., 2012; Biro et al., 2013; Cabrera et al., 2014; Arthur et al., 2016; Eckert-Lind et al., 2020). Among a cohort of girls in the United States longitudinally followed to assess pubertal markers, the mean age at menarche was 12.25 years. The age at onset of puberty varies between ethnic groups. Hispanic girls were more likely to have earlier menarche than Black girls, whereas White and Asian girls were more likely to have their first period at older ages. In this cohort, girls with high BMI achieved menarche approximately 0.3 years earlier than girls with normal weight. The tempo of puberty was slower among girls with earlier breast development; the age at menarche has minimally declined over the past 20 years (Biro et al., 2018).

Analogous studies of boys are limited, but no striking sex differences in secular trends in puberty and growth are apparent. Using both genital staging and the orchidometer, the Copenhagen Puberty Study reported pubertal onset occurring 3 months earlier in Danish boys and that obesity advanced the onset of testicular enlargement (Goldberg et al., 2020). However, other studies suggest that obesity delays onset of puberty in boys.

Pubertal timing is associated with long-term health outcomes. Early thelarche and menarche in girls are associated with increased risks for breast cancer (Goldberg et al., 2020). Earlier age at puberty was associated with increased risks for prostate cancer in boys and endometrial cancer in girls (Day et al., 2017). This has been attributed to longer duration of sex steroid exposure. Women with late menarche have an increased risk to develop osteoporosis (Parker et al., 2014).

Puberty

To understand the behavior of early adolescents, one must become familiar with the normal pattern of puberty and appreciate the dramatic physical changes that are a part of it. In the United States, puberty begins for most girls between the ages of 8 and 13 years with the development of breast buds (thelarche). It is normal, however, for some adolescents, particularly African American girls, to have the onset of pubic hair development (adrenarche) before breast development. Pubescence starts later for boys and begins with testicular enlargement followed by lengthening of the penis and pubic hair development. The majority of boys have entered puberty, by evidence of increased testicular volume, by or before age 14; some boys start puberty as early as 8 or 9 years. The progress of puberty can be followed on physical examination by assigning a Tanner stage, or sexual maturation rating, from 1 to 5 for breast maturation and pubic hair development in girls and genital maturation and pubic hair development in boys (see Table 22-2). Puberty is typically completed within 4 to 5 years and follows a well-described pattern that is summarized in Figure 22-1 and Table 22-2. For instance, menarche occurs about 2 years after thelarche: normally between the ages of 10 to 16 years with an average age of onset at 12.5 years.

Several factors affect the timing of pubertal events and menarche, such as health, nutrition, body mass index, ethnicity and environmental conditions. As a group, African American girls enter puberty first, followed by Mexican American and then non-Hispanic white girls. Similarly, African American boys have been shown to enter adrenarche and complete genital development before Mexican American and white American boys. Because of these ethnic differences, standards for normal sexual maturation are being developed for various ethnic groups. In general, however, there has been a “secular” trend over the past century toward earlier puberty and larger growth. This trend is largely attributed to better health and nutrition, although some specialists hypothesize that environmental chemicals as well as hormones in animal and beauty products may be contributing to an earlier onset of pubertal development in some populations. As more studies demonstrate that boys and girls are developing earlier than the commonly used reference norms of Marshall and Tanner, the age cutoffs for precocious puberty are being debated and may be lowered.

Introduction

Over a woman’s lifetime, dramatic changes occur in the female body due to both normal physiologic changes and pathologic conditions. These can have a large impact on how a woman perceives her body. It has been found that 68.5% of women presenting for routine gynecologic care reported a body image-related concern. In this article, we will look at the interaction of body image and normal physiology and pathologic gynecologic conditions over the female life span. Pregnancy, cosmetic and cancer-related breast surgery, and cancer are covered elsewhere in this encyclopedia.

The hormonal agents

Puberty is a product of the human hormonal system. While virtually all hormonal structures activate and change during adolescence, three important hormonal axes determine the puberty metamorphosis, including the hypothalamic-pituitary-gonadal (HPG) axis, the hypothalamic-pituitary-adrenal (HPA) axis, and the growth hormone (GH) axis (Carswell & Stafford, 2016; Lee & Styne, 2012).

The HPG axis reaches maturation during puberty and is responsible for sexual development, thelarche (onset of breast development) and menarche (onset of menses) through the release of estradiol [E2 (estrogen)] from the ovary and testosterone (T) from the testes, respectively (Carswell & Stafford, 2016; Lee & Styne, 2012). Independent of the HPG axis, the HPA axis oversee the production of androgens from the adrenal glands, leading to the growth of terminal hair in the axillary and pubic areas, development of body odor, and increased sebum production and development of acne (Carswell & Stafford, 2016). As its name suggests, the GH axis—coupled with sex steroids—is responsible for growth spurts during puberty, including bone and muscle growth (Carswell & Stafford, 2016).

Pubertal Suppression

Physiologically, pubertal progression begins with GnRH pulses from the hypothalamus. This results in production of gonadotropins, luteinizing hormone and follicle stimulating hormone, from the pituitary. The gonadotropins then stimulate the gonads to produce sex hormones, namely testosterone in natal males and estrogen in natal females. Clinically, the first sign of puberty in girls is thelarche, with development of breast tissue. On average, thelarche occurs between the ages of 8 and 13 years. In boys, the first sign of puberty is testicular enlargement. In natal males, secondary sex characteristics typically appear between the ages of 9 and 14 years. The five-point Tanner staging system denotes progression of physical changes through puberty. Tanner stage 1 is prepubertal and Tanner stage 5 signifies full pubertal development.7

Clinical pubertal suppression involves administration of GnRH agonists. The lay term for GnRH agonists is “blockers” as they “block” puberty. Treatment with a GnRH agonist results in tonic, rather than pulsatile levels of GnRH. Without pulsatile GnRH, the hypothalamic–pituitary–gonadal axis is suppressed. With this suppression, the amount of sex hormone (testosterone in natal males and estrogen in natal females) produced by the gonads decreases and pubertal progression stops.7 In the United States, clinicians use two GnRH agonists, leuprolide (brand name Lupron) and histrelin (brand name Supprelin). Leuprolide, an injectable GnRH agonist is administered once a month or once every 3 months. Histrelin, an implant placed subcutaneously, delivers medication for up to 2 years. Histrelin can be implanted with or without sedation.4

Pubertal suppression with GnRH agonists first saw clinical use in patients with precocious puberty to stop pubertal progression and provide additional time for the child to grow.8 In 2006, a group in the Netherlands created a protocol for the use of GnRH agonists in transgender patients as young as 12 years.9 The goal was to suppress puberty in order to treat gender dysphoria.4 In 2009, the Endocrine Society, along with the World Professional Association for Transgender Health and several other organizations, created a clinical practice guideline recommending the use of GnRH agonists for pubertal suppression in transgender children. However, instead of stipulating an age for initiating the use of GnRH agonists, the guidelines recommended their use as early as Tanner 2, which can occur before 12 years of age.10 The Endocrine Society also recommended psychological assessments of patients to ascertain their readiness for treatment and ensure that mental health comorbidities be addressed along with gender dysphoria. The guidelines further recommended ongoing patient follow-up by a mental health provider throughout medical treatment.10

Currently, GnRH agonists are the standard of care for pubertal suppression in transgender youth.4 Clinicians generally believe that blocking puberty with GnRH agonists is fully reversible. However, there are limited safety and efficacy studies, and medical science has virtually no data on the safety or effectiveness of GnRH agonists in transgender children younger than 12 years.1

GnRH agonists do have known side effects. Approximately a month after the initial administration, a surge of sex hormones, testosterone in natal males and estrogen in natal females, can occur, resulting in acceleration of natal puberty or even initiation of menstruation, with substantial distress for the patient. An additional leuprolide injection 2 weeks after the initial injection or implant insertion counteracts these side effects. Local site reactions (i.e., pain, swelling, abscess), rash, hot flushes, and sweating can all occur, as well.4

Physical changes associated with puberty

Secondary sexual maturation and endocrine changes during pubertal development include thelarche, gonadarche, pubarche, and adrenarche. Increased growth rate is one of the first signs of puberty and peak height velocity (PHV) occurs relatively early in female puberty (Tanner and Davies, 1985). Thelarche, the onset of breast development, is caused by an increase in the secretion of ovarian estrogen and is often the first sign of puberty noted in girls during routine evaluations (Styne, 2011). Isolated premature thelarche may occur unrelated to normal GnRH dependent puberty. Gonadarche marks the increase in sex steroid secretion from the gonads under the control of the hypothalamic pituitary axis; in boys, gonadarche is associated with increased testicular volume (Styne, 2011). The maturation of the adrenal gland and increased secretion of adrenal androgens, adrenarche, contributes to pubarche, the onset of pubic hair development, which is independent of the HPG axis.

The staging system Tanner developed to describe normal progression of puberty in males and females over 50 years ago is utilized for clinical descriptions in terms of Sexual Maturation Rating (SMR) or Tanner Stages (Marshall and Tanner, 1969, 1970). Marshall and Tanner also observed variations in children's progression through these stages, specifically describing differences in pubertal timing, described as “variation in the chronological age at which adolescence begins and different stages of physical maturity are reached” and pubertal tempo, described as “variation in the time taken to pass through the various stages of development” (Marshall and Tanner, 1969).

8.2 Delayed puberty

Delayed puberty is arbitrarily defined as the lack of signs of secondary sexual characteristics by the age of ∼13 years in girls (lack of thelarche) and ∼14 years in boys (testicular volume < 3 mL) (Argente, 1999; Sedlmeyer & Palmert, 2002; Traggiai & Stanhope, 2002). Practically, it is defined as a delay in the onset, progression, or completion of pubertal development. Puberty is considered delayed if the elapsed time between the onset of the first pubertal sign to the final stage of puberty (pubertal arrest) exceeds 4–5 years (Argente, 1999). Moreover, a boy is said to have delayed puberty if a testicular volume of >3 mL was not attained by the age of 14 years (Marshall & Tanner, 1970). The absence of menarche in a girl by the age of 15 years (primary amenorrhoea) or a failure of pubertal progression warrants urgent investigation (Wolfenden & Ryan, 2014). Delayed puberty is classified into pubertal delay and pubertal failure; their potential causes are listed in Table 3.

Deviations of pubertal development from the average timing (precocious or delayed) or tempo can be associated with an adverse psychological disorders. Previous studies have shown that early or late puberty can be associated with negative outcomes (mainly internalizing and externalizing problems), eating disorders, anxiety, and sexual behavior in both sexes (Graber, Seeley, Brooks-Gunn, & Lewinsohn, 2004; Miller, Norton, Fan, & Christopherson, 1998; Zehr, Culbert, Sisk, & Klump, 2007).

1 Introduction

Despite a strong genetic component, environmental factors such as general health, nutritional status and endocrine-disrupting chemicals (EDC) (Lucaccioni et al., 2020; Sidorkiewicz, Zareba, Wolczynski, & Czerniecki, 2017) are known to impact the timing (age of attainment of pubertal milestones) and tempo (time taken from puberty onset to complete sexual maturation) of puberty (Buck Louis et al., 2008). However, much remains to be elucidated in the complicated pathways related between puberty and environmental factors like nutrition (Munoz-Calvo & Argente, 2016; Toppari & Juul, 2010). A high prevalence of stunting, macronutrient and micronutrient deficiencies are well-recognized problems among adolescents in developing countries (Akseer, Al-Gashm, Mehta, Mokdad, & Bhutta, 2017). These problems are further exacerbated by the higher nutritional requirements for growth and development at this time (Das et al., 2017). Predicted ordered changes in female breast development or male genital development encompass the sequelae of pubertal events most commonly classified into five categories known as the Sexual Maturity Rating or Tanner Stages (Wolf & Long, 2016). The first physical changes are due to central puberty or true puberty resulting from the re-activation of the hypothalamic-pituitary-gonadal axis. This triggers thelarche (onset of breast development) and gonadarche (ovary and testicular development) (Biro, 2007; Bordini & Rosenfield, 2011). (Li et al., 2017; Moodie et al., 2020). Next is pubarche (first appearance of pubic hair) which can stem from adrenarche (increased secretion of adrenal androgens) or gonadarche (Biro, 2007; Bordini & Rosenfield, 2011).

As a public health indicator, declines in pubertal age have been associated with improvements in socioeconomic status and better living conditions (Golub et al., 2008). Historical records from developed countries on age-at-menarche (AAM) date back more than 100 years. Among female adolescents, secular trends in AAM show a trend towards younger menarche stabilizing since 1960 at a mean age of 12–13 years (Parent et al., 2003; Patton & Viner, 2007). Contemporary secular trends towards a younger mean age for female puberty onset coincide with increasing trends in the prevalence of obesity (Eckert-Lind et al., 2020). An overwhelming lack of puberty research among boys precludes the knowledge of their secular trends (Tinggaard et al., 2012). Disproportionally, the research on puberty relates to high-income countries over low- and middle-income countries (LMIC); however, a recent systematic review on pubertal timing among those living in LMIC noted that contemporary age of attainment of pubertal milestones was congruent with published puberty research in high-income settings (Moodie et al., 2020). Pooled age estimates from this systematic review for puberty onset in girls was 10.4 years (95%CI: 9.2; 11.6); puberty onset in boys was 11.1years (95%CI: 10.3; 11.7) and age at menarche was 12.3 years (95%CI: 11.9; 12.6). The usual sequence of pubertal milestones differs by sex with the peak height velocity (PHV) associated with the pubertal growth spurt occurring later in males than females. In girls, the PHV occurs after puberty onset of breast and pubic hair development with bone senescence occurring shortly after menarche (Wolf & Long, 2016) (Abreu & Kaiser, 2016; Castellano & Tena-Sempere, 2016). In boys, PHV occurs well after puberty onset around Tanner Stage Genital 4 and Public Hair Stage 3. (Wolf & Long, 2016). Altered pubertal timing has also been associated with later health and psychological problems (Zhu & Chan, 2017).

Although the order of pubertal sequalae is consistent among boys and girls, their timing can vary. Puberty data from a slum in Karachi, Pakistan have been published recently ( Campisi et al., 2020); however, puberty data on rural Pakistani adolescents do not currently exist. To fill this gap, we aim to determine the observed age at pubertal milestones and the relationship between nutritional status and pubertal milestones among children and adolescents living in the rural district of Matiari, Pakistan.