{"id":1285,"date":"2013-10-10T20:01:25","date_gmt":"2013-10-10T20:01:25","guid":{"rendered":"http:\/\/jacobimed.org\/NS\/?page_id=1285"},"modified":"2013-10-10T20:01:25","modified_gmt":"2013-10-10T20:01:25","slug":"normal-onset-of-puberty-lalwani-et-al","status":"publish","type":"page","link":"https:\/\/jacobimed.org\/old\/ambulatory\/mlove\/curriculumprevention\/adolescent-medicine\/normal-onset-of-puberty-lalwani-et-al\/","title":{"rendered":"Normal Onset of Puberty, Lalwani et al"},"content":{"rendered":"

 <\/p>\n

\n

Normal onset of puberty<\/span><\/strong><\/p>\n

\nHave definitions of onset changed?<\/span><\/strong><\/p>\n


\nSasmira Lalwani, MD<\/strong> <\/span>a<\/a>
\n<\/span><\/sup>, <\/span><\/sup>*<\/a>
\n<\/span><\/sup>
\nRichard H. Reindollar, MD<\/strong> <\/span>a<\/a>,b<\/a><\/span><\/sup>
\nAnn J. Davis, MD<\/strong> <\/span>a<\/a>,b<\/a><\/span><\/sup> <\/span><\/p>\n

<\/p>\n
\n<\/span><\/div>\n

a<\/span><\/sup> <\/span><\/sup>Division
\nof Reproductive Endocrinology and Infertility
\nBeth Israel Deaconess Medical Center
\n330 Brookline Avenue
\nBoston, MA 02215, USA<\/p>\n

<\/span>b<\/span><\/sup> <\/span><\/sup>Department
\nof Obstetrics and Gynecology
\nHarvard Medical School
\nBoston, MA 02215, USA<\/span> <\/p>\n

\n
\n<\/div>\n\n\n\n\n
\n

*<\/span><\/sup> Corresponding author<\/span><\/span><\/p>\n<\/td>\n<\/tr>\n

\n

E-mail address:<\/span><\/em>  slalwani@caregroup.harvard.edu<\/span><\/span><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n\n\n\n\n
\n

This article was originally
\n published in Infertility and Reproductive Medicine Clinics of North
\n America<\/em> 14:1, 2003.<\/span><\/span><\/p>\n<\/td>\n<\/tr>\n

\n

PII S0889-8545(03)00025-1<\/span><\/span><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Puberty is the sequence of events in an individual’s life that culminates in
\nphysical, sexual, and emotional maturation. This sequence of events is caused
\nby the maturation of the hypothalamic-pituitary-gonadal (HPG) axis.<\/p>\n

Maturation begins with a significant rise in gonadotropin secretion during
\nfetal life that persists during infancy and goes into a quiescent phase during
\nchildhood. The onset of puberty results from the episodic release of
\nluteinizing hormone (LH) and follicular stimulating hormone (FSH). This release
\nreflects the intermittent release of GnRH from the hypothalamus in greater
\nquantities and more frequent pulses.<\/p>\n

The physiology of puberty<\/h3>\n

\nThe fetal, infancy, and childhood period<\/em><\/strong> <\/p>\n

By 10 weeks of gestation, GnRH is
\npresent in the hypothalamus and functionally active after 20 weeks of
\ngestational age [1]<\/sup><\/a>
\n<\/span>, and the pituitary responds to GnRH stimulation by secreting LH and
\nFSH. GnRH and gonadal secretion progressively increase and stimulate gonadal
\nmaturation and hormone production. At birth, the levels of gonadotropins and
\nsex steroid hormones are high, but they decline after a few days. In response
\nto the decline in circulating sex steroids originating from the placenta, the
\ngonadotropin levels start to rise again during the first week of life. During
\nthe next several weeks, levels of gonadotropins and gonadal hormones continue
\nto be higher than the levels in older children. This suggests that the gonads
\nare responsive to stimulation and are fully functional. Gonadotropins and sex
\nsteroids peak at 2 to 3 months of age, after which they drop to low levels for
\nmany years. The fall in gonadotropin levels occurs not only because of an
\nadjustment in the negative feedback mechanism but also because of probable
\nCentral Nervous System (CNS) control of gonadotropin secretion (this fall in
\ngonadotropin levels also is seen in agonadal children). Even though
\ngonadotropin levels are lowest during mid-childhood, measurable amounts of
\ngonadotropin are present, indicating some amount of episodic release [2]<\/sup><\/a>
\n<\/span>. Hence, a small amount of sex steroids, including estrogen, may be
\npresent in some children [3]<\/sup><\/a>
\n<\/span>.<\/p>\n

\nPuberty<\/em><\/strong>
\nGonadotropin-releasing hormone and gonadotropins<\/em> <\/p>\n

The HPG axis is active in fetal
\nlife, and the pituitary and gonads are ready to respond with the appropriate
\nstimulation by GnRH and the gonadotropins, respectively. Control is at the
\nlevel of GnRH stimulation or a higher CNS loci. Preceding the onset of and
\nduring puberty, the mean levels of the gonadotropins rise, reflecting the increased
\nepisodic release of gonadotropins in response to pulsatile GnRH secretion. Due
\nto this alteration in GnRH secretion, gonadotropin secretion is enhanced. A low
\nlevel of gonadotropin secretion, with a low frequency and amplitude that
\nincrease during sleep, is present in prepubertal children [1]<\/sup><\/a>
\n[2]<\/sup><\/a>
\n[3]<\/sup><\/a>
\n[4]<\/sup><\/a>
\n[5]<\/sup><\/a>
\n<\/span>. As pubertal maturation progresses, the frequency and amplitude of
\nthese pulses increase. During early puberty, these pulses are seen more
\nfrequently during sleep than in the wakeful state. These change are more
\ndramatic for LH than for FSH, with the rise in LH being greater than FSH during
\npuberty [6]<\/sup><\/a>
\n<\/span>. In adults, the episodic rise in LH occurs every 90 minutes and lasts
\nfor approximately 20 minutes. The episodic release of FSH occurs less
\ndramatically and is greater during sleep. These episodic phenomena are produced
\nby the maturation of the CNS-stimulating influences that affect the GnRH pulse
\ngenerator. Thus, pubertal change of the hypothalamus and the pituitary involves
\nthe increase of GnRH, LH, and FSH pulsatile secretion rather than the onset of
\nsecretion. The secretion of GnRH (12–18 times every 24 hours) is regulated by a
\nregion in the arcuate nucleus of the medial basal hypothalamus. At the onset of
\npuberty, GnRH stimulation exerts a priming effect on the pituitary and causes a
\nprogressive increase in gonadotropins. This increased responsiveness also is
\naccompanied by an increase in GnRH receptors in the pituitary.<\/p>\n

Adult levels of LH and FSH are
\nregulated by gonadal hormone secretion through a negative feedback mechanism
\nand in the middle of the menstrual cycle through a positive feedback mechanism.<\/p>\n

\nSex steroids<\/em> <\/p>\n

The rise of gonadotropins and of
\nsex steroids from the gonads and the adrenal cortex occurs before the onset of
\npuberty. The increase in adrenal androgen production, or adrenarche, is
\nresponsible for the onset of pubic hair growth (pubarche). The increase in
\ngonadal sex steroid production is known as gonadarche.<\/p>\n

\nAdrenarche<\/em> .  The adrenal androgens may be the first hormones
\nto be elevated in puberty. The appearance of pubic and axillary hair, acne, and
\nbody odor may be the result of adrenal androgen production since these findings
\ncan occur without the presence of gonadal steroids and before any other signs
\nof pubertal development.<\/p>\n

The cause of adrenarche is not
\nknown. Elevated gonadotropin secretion does not cause an increase in
\nadrenocorticotropic (ACTH) secretion. ACTH levels also do not increase at
\nadrenarche; however, the response of the adrenal steroids to ACTH changes. The
\nandrogens are more sensitive to ACTH stimulation than the other adrenal
\nsteroids, and this response parallels the development of the adrenal zona
\nreticularis.<\/p>\n

\nGonadarche<\/em> .  Gonadarche occurs due to the elevation in
\ncirculating gonadal steroids, especially estrogens in girls, in response to
\ngonadotropin stimulation.<\/p>\n

Other factors influencing the onset of puberty<\/em> <\/p>\n

Leptin, a hormone derived from
\nadipose tissue, plays a role in body composition. It is hypothesized that body
\nmass and composition regulate the onset of puberty. Because leptin levels rise
\nduring puberty, there is considerable interest in the role of leptin in the
\nonset of puberty [7]<\/sup><\/a>
\n[8]<\/sup><\/a>
\n<\/span>.<\/p>\n

Activin and Follistatin are two
\nother hormones that regulate follicular maturation and atresia. Although the
\nlevels of these hormones do not change during puberty, they do change during
\nadulthood [9]<\/sup><\/a>
\n<\/span>.<\/p>\n

Other factors, such as excessive
\nexercise, inadequate nutrition, and psychiatric illnesses (eg, anorexia
\nnervosa), are associated with hypogonadotropic states that alter the onset of
\npuberty.<\/p>\n

Genetic regulation of the timing of
\npuberty is seen in a correlation between the ages at which a mother and
\noffspring attain pubertal milestones [10]<\/sup><\/a>
\n<\/span>. Studies of twins demonstrate that pubertal milestones display more
\nsimilarity between monozygotic twins than dizygotic twins [11]<\/sup><\/a>
\n[12]<\/sup><\/a>
\n[13]<\/sup><\/a>
\n[14]<\/sup><\/a>
\n<\/span>.<\/p>\n

Patterns of onset: have definitions changed?<\/h3>\n

The pubertal sequence of events
\nfollows a certain pattern. Usually the first sign is accelerated growth,
\nfollowed by breast development, adrenarche, and menarche. This sequence of
\nevents on average requires a period of 4.5 years (range 1.5–6 years). Pubertal
\ndevelopment has started occurring earlier, partly due to better socioeconomic
\nconditions, especially nutritional status. Racial differences do exist in the
\nonset and progression of puberty, with secondary sexual characteristics
\ndeveloping earlier in African-American girls than in white girls.<\/p>\n

Previously, it was accepted that
\nnormal puberty in girls does not begin before 8 years of age. In 1997, the
\nAmerican Academy of Pediatrics published a cross-sectional study of pubertal
\ndevelopment in American girls who were seen in pediatric office practices. This
\nlarge multicenter study of 17,077 girls consisted of 90.4% white Americans and
\n9.6% black Americans [10]<\/sup><\/a>
\n<\/span>. Table
\n1<\/a> <\/span>contains the important findings of the study.<\/p>\n

 <\/p>\n\n\n<\/col>\n<\/col>\n<\/col>\n<\/colgroup>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
\n

Table 1.<\/strong>   Cross-sectional study of
\n pubertal development in black and white American girls<\/strong><\/span><\/p>\n<\/td>\n<\/tr>\n<\/thead>\n

\n

Abbreviations:<\/span><\/em> y, years.<\/span><\/span><\/p>\n<\/td>\n<\/tr>\n<\/tfoot>\n

\n

Pubertal event<\/strong><\/span><\/strong><\/p>\n<\/td>\n

\n

Black American girls<\/strong><\/span><\/strong><\/p>\n<\/td>\n

\n

White American girls<\/strong><\/span><\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

Breast or pubic hair<\/span><\/p>\n<\/td>\n<\/tr>\n

\n

     Age 7 y<\/span><\/p>\n<\/td>\n

\n

27.2%<\/span><\/p>\n<\/td>\n

\n

6.7%<\/span><\/p>\n<\/td>\n<\/tr>\n

\n

     Age 8 y<\/span><\/p>\n<\/td>\n

\n

48.3%<\/span><\/p>\n<\/td>\n

\n

14.7%<\/span><\/p>\n<\/td>\n<\/tr>\n

\n

Menarche<\/span><\/p>\n<\/td>\n<\/tr>\n

\n

Age 11 y<\/span><\/p>\n<\/td>\n

\n

27.9%<\/span><\/p>\n<\/td>\n

\n

13.4%<\/span><\/p>\n<\/td>\n<\/tr>\n

\n

Age 12 y<\/span><\/p>\n<\/td>\n

\n

62.1%<\/span><\/p>\n<\/td>\n

\n

35.2%<\/span><\/p>\n<\/td>\n<\/tr>\n

\n

Thelarche (mean age)<\/span><\/p>\n<\/td>\n

\n

8.87 y<\/span><\/p>\n<\/td>\n

\n

9.96 y<\/span><\/p>\n<\/td>\n<\/tr>\n

\n

Adrenarche (mean age)<\/span><\/p>\n<\/td>\n

\n

8.78 y<\/span><\/p>\n<\/td>\n

\n

10.51 y<\/span><\/p>\n<\/td>\n<\/tr>\n

\n

Menarche (mean age)<\/span><\/p>\n<\/td>\n

\n

12.16 y<\/span><\/p>\n<\/td>\n

\n

12.88 y<\/span><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n

The data revealed that the
\nprevalence of breast or pubic hair before 8 years of age was 27% in black girls
\nand 7% in white girls. By 9 years of age, 48% of black girls and 15% of white
\ngirls showed some sign of pubertal development. The mean age of menarche—12.2
\nyears in black girls and 12.9 years in white girls—did not differ significantly
\nfrom other reports. This study suggests that even though puberty is occurring
\nearlier than previously thought, menarche is not occurring earlier and puberty
\nis not completed earlier. In girls who showed an earlier onset of puberty,
\ngrowth may be taking place at a slower pace or initial breast development may
\nnot be associated with the onset of real puberty. Maybe this earlier onset can
\nbe attributed to a different subset of the population, which influenced the
\noverall data. A contributing factor could be that these data are derived from
\noffice practices instead of a random sampling of the population.<\/p>\n

As a result of this study, new
\nguidelines were recommended to redefine precocious puberty in girls from the
\nonset of breast development before 8 years of age to the onset of breast or
\npubic hair before 7 years of age in white girls and 6 years of age in black
\ngirls [11]<\/sup><\/a>
\n<\/span>. We should be cautious in redefining the onset of puberty based on one
\nstudy. Precocious puberty can be the result of a serious disorder, and
\ndiagnosis involves more criteria than age. Puberty that progresses so rapidly
\nthat growth and development are clearly excessive for age should be evaluated
\nand therapy to suppress pubertal development should be considered.<\/p>\n

Stages of pubertal development<\/h3>\n

In general, the first sign of puberty
\nis an acceleration of growth followed by breast budding. Breast development
\nfollows a series of events, with adrenarche usually following thelarche by 2
\nyears. In some cases the sequence may be reversed, with pubic hair being the
\nfirst sign of puberty in approximately 20% of girls. Menarche is a late event
\nthat occurs during deceleration of the growth phase. About 90% of menstrual
\ncycles may not be ovulatory until 6 to 7 years after menarche. Table
\n2<\/a> <\/span>outlines the mean developmental pattern of puberty in girls [10]<\/sup><\/a>
\n[11]<\/sup><\/a>
\n[12]<\/sup><\/a>
\n[13]<\/sup><\/a>
\n[14]<\/sup><\/a>
\n[15]<\/sup><\/a>
\n[16]<\/sup><\/a>
\n[17]<\/sup><\/a>
\n[18]<\/sup><\/a>
\n<\/span>.<\/p>\n

 <\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
\n

Table 2.<\/strong>   Sequence of pubertal
\n events in girls<\/strong><\/span><\/p>\n<\/td>\n<\/tr>\n<\/thead>\n

\n

Pubertal event<\/strong><\/span><\/strong><\/p>\n<\/td>\n

\n

Mean age<\/strong><\/span><\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

Breast development (Tanner stage 2)<\/span><\/p>\n<\/td>\n

\n

10.0–10.5<\/span><\/p>\n<\/td>\n<\/tr>\n

\n

Pubic hair growth (Tanner stage 2)<\/span><\/p>\n<\/td>\n

\n

10.3–10.8<\/span><\/p>\n<\/td>\n<\/tr>\n

\n

Maximum growth rate<\/span><\/p>\n<\/td>\n

\n

11.2–11.7<\/span><\/p>\n<\/td>\n<\/tr>\n

\n

Maximum rate of weight gain<\/span><\/p>\n<\/td>\n

\n

11.7–12.2<\/span><\/p>\n<\/td>\n<\/tr>\n

\n

Breast development (Tanner stage 3)<\/span><\/p>\n<\/td>\n

\n

11.3–11.8<\/span><\/p>\n<\/td>\n<\/tr>\n

\n

Pubic hair growth (Tanner stage 3)<\/span><\/p>\n<\/td>\n

\n

11.4–11.9<\/span><\/p>\n<\/td>\n<\/tr>\n

\n

Onset of axillary hair<\/span><\/p>\n<\/td>\n

\n

12.3–12.8<\/span><\/p>\n<\/td>\n<\/tr>\n

\n

Menarche<\/span><\/p>\n<\/td>\n

\n

12.6–13.1<\/span><\/p>\n<\/td>\n<\/tr>\n

\n

Breast development (Tanner stage 4)<\/span><\/p>\n<\/td>\n

\n

12.5–13.0<\/span><\/p>\n<\/td>\n<\/tr>\n

\n

Pubic hair growth (Tanner stage 4)<\/span><\/p>\n<\/td>\n

\n

12.5–13.0<\/span><\/p>\n<\/td>\n<\/tr>\n

\n

Regular menses<\/span><\/p>\n<\/td>\n

\n

13.7–14.2<\/span><\/p>\n<\/td>\n<\/tr>\n

\n

Breast development (Tanner stage 5)<\/span><\/p>\n<\/td>\n

\n

14.0–14.5<\/span><\/p>\n<\/td>\n<\/tr>\n

\n

Pubic hair growth (Tanner stage 5)<\/span><\/p>\n<\/td>\n

\n

14.0–14.5<\/span><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n

The following sections describe the
\nstages of pubertal development:<\/p>\n\n\n\n\n\n\n
\n

   <\/span><\/p>\n<\/td>\n

\n

Growth and skeletal maturation<\/span><\/p>\n<\/td>\n<\/tr>\n

\n

   <\/span><\/p>\n<\/td>\n

\n

Thelarche (breast development)<\/span><\/p>\n<\/td>\n<\/tr>\n

\n

   <\/span><\/p>\n<\/td>\n

\n

Adrenarche<\/span><\/p>\n<\/td>\n<\/tr>\n

\n

   <\/span><\/p>\n<\/td>\n

\n

Menarche<\/span><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

\nGrowth and skeletal maturation<\/em><\/strong> <\/p>\n

In girls, the growth spurt occurs
\nearly compared with boys and occasionally precedes thelarche. Peak growth
\noccurs when breast development is between Tanner stages 2 and 3. Sex steroids,
\nespecially estrogen, play an important role in the skeletal growth that occurs
\nduring puberty in both women and men. Estrogen is a potent stimulator of bone
\ngrowth, and it is necessary for the closure of the epiphysis. Individuals with
\naromatase deficiency or estrogen receptor mutations continue to grow into
\nadulthood and become very tall [14]<\/sup><\/a>
\n[15]<\/sup><\/a>
\n[16]<\/sup><\/a>
\n[17]<\/sup><\/a>
\n[18]<\/sup><\/a>
\n[19]<\/sup><\/a>
\n[20]<\/sup><\/a>
\n[21]<\/sup><\/a>
\n<\/span>. Estrogen also plays a critical role in the accumulation of bone mass,
\nwith peak bone mass attained late in puberty. Besides estrogen, the presence of
\ngrowth hormone and insulin-like growth factor-I are necessary for growth [22]<\/sup><\/a>
\n<\/span>.<\/p>\n

\nThelarche<\/em><\/strong> <\/p>\n

The average of onset of breast
\nbudding is approximately 10 years of age and reflects the progressive increase
\nin estrogen stimulation and production. Breast development follows a
\nwell-recognized sequence of events characterized by the following Tanner stages
\n[23]<\/sup><\/a>
\n<\/span>:<\/p>\n\n\n\n\n\n\n\n
\n

   <\/span><\/p>\n<\/td>\n

\n

Absence of breast bud<\/span><\/p>\n<\/td>\n<\/tr>\n

\n

   <\/span><\/p>\n<\/td>\n

\n

Presence of breast bud only<\/span><\/p>\n<\/td>\n<\/tr>\n

\n

   <\/span><\/p>\n<\/td>\n

\n

Enlargement of entire breast mound<\/span><\/p>\n<\/td>\n<\/tr>\n

\n

   <\/span><\/p>\n<\/td>\n

\n

Secondary areolar mound on top of the primary mound<\/span><\/p>\n<\/td>\n<\/tr>\n

\n

   <\/span><\/p>\n<\/td>\n

\n

Adult mature breast contour, secondary mound no longer
\n evident<\/span><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

\nAdrenarche<\/em><\/strong> <\/p>\n

The appearance of pubic hair is the
\nnext change seen in puberty. The texture of the pubic hair is longer and
\ncoarser than the body hair of childhood. Pubic hair development, which reflects
\nincreased androgen production, is characterized by the following Tanner stages [23]<\/sup><\/a>
\n<\/span>.<\/p>\n\n\n\n\n\n\n\n
\n

   <\/span><\/p>\n<\/td>\n

\n

Nonsexual, general body hair<\/span><\/p>\n<\/td>\n<\/tr>\n

\n

   <\/span><\/p>\n<\/td>\n

\n

Long, coarse, pigmented hair, usually appearing along the
\n labia majora<\/span><\/p>\n<\/td>\n<\/tr>\n

\n

   <\/span><\/p>\n<\/td>\n

\n

Greater concentration of coarse, long hair extending to
\n the mons pubis<\/span><\/p>\n<\/td>\n<\/tr>\n

\n

   <\/span><\/p>\n<\/td>\n

\n

Abundance of coarse, dark pubic hair on the mons and labia<\/span><\/p>\n<\/td>\n<\/tr>\n

\n

   <\/span><\/p>\n<\/td>\n

\n

Pubic hair present in an adult pattern, an inverted
\n triangle extending to the thighs<\/span><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

\nMenarche<\/em><\/strong> <\/p>\n

The mean interval between breast
\nbudding and the onset of menses is approximately 2 years. This may vary: the
\nearlier the thelarche, the longer until menarche [24]<\/sup><\/a>
\n<\/span>. Menarche depends on hormonal levels during early puberty, with higher
\nlevels leading to an earlier onset [25]<\/sup><\/a>
\n<\/span>. Menarche most commonly occurs during stage 3 or 4 of breast
\ndevelopment.<\/p>\n

The median age of the onset of
\nmenses in American girls is 12.8 years (range of 9.1–17.7 years) [13]<\/sup><\/a>
\n[26]<\/sup><\/a>
\n<\/span>. The menses following menarche are usually anovulatory, with 25% to 50%
\nof girls anovulatory 4 years after menarche [27]<\/sup><\/a>
\n[28]<\/sup><\/a>
\n<\/span>.<\/p>\n

Menarche occurs after the growth
\nspurt has passed. Slower growth (on average, 6 cm or 2.4 in) occurs after
\nmenarche.<\/p>\n

\nVariations<\/em><\/strong> <\/p>\n

Variation in the duration of
\npubertal development represents diversity in the rate of maturation and
\nattainment of full reproductive function. Complete breast development can take
\n3 years or longer, with 3 to 4 years required for pubic hair development.
\nPrepubertal development of sexual hair as an isolated event is known as
\npremature pubarche, and isolated breast development is known as premature
\nthelarche. Both can represent the onset of precocious puberty; however, once
\nprecocious puberty is ruled out, these events by themselves are innocuous.<\/p>\n

Summary<\/h3>\n

Puberty is the sequence of events
\nthat culminates in the ability to procreate. It is widely accepted that the
\nonset of puberty in girls occurs on average at 8 years of age and that onset
\nprior to 8 years of age is precocious puberty. As a result of the
\ncross-sectional study by the American Association of Pediatrics, a movement
\nexists to change the age limit of the onset of puberty to 6 years of age in
\nblack girls and 7 years of age in white girls. We should be cautious in
\nadhering to strict age limits when diagnosing precocious puberty. Also the rapidity
\nand progression of puberty should be evaluated, and if appropriate, therapy to
\nsuppress pubertal development considered.<\/p>\n

References<\/strong><\/p>\n

[1].<\/span>
\nRamussen DD, Gambacciani M, Swarts W, Tueros VS, Yen SS. Pulsative
\ngonadotropin-releasing hormone release from the human mediobasal hypothalamus
\nin vitro: opiate receptor-mediated suppression. Neuroendocrinology
\n1989;49:150-6.<\/span>   Abstract<\/span><\/a>
\n[2].<\/span> Wu
\nFCW, Butler GE, Kelnar CJH, et al. Patterns of pulsatile leutinising hormone
\nand follicle-stimulating hormone secretion in prepubertal (mid-childhood) boys
\nand girls and patients with idiopathic hypogonadotropic hypogonadism (Kallman’s
\nsyndrome): a study using an ultrasensitive time-resolved immunofluorometric
\nassay. J Clin Endocrinol Metab 1991;72:1229-37.<\/span>  
\n[3].<\/span> Klein
\nKO, Baron J, Colli MJ, et al. Estrogen levels in childhood determined by an
\nultrasensitive recombinant cell bioassay. J Clin Invest 1994;94:2475-80.<\/span>
\n  Abstract<\/span><\/a>
\n[4].<\/span>
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\n  Abstract<\/span><\/a><\/p>\n<\/div>\n","protected":false},"excerpt":{"rendered":"

  Normal onset of puberty Have definitions of onset changed? Sasmira Lalwani, MD a , * Richard H. Reindollar, MD a,b Ann J. Davis, MD a,b a Division of Reproductive Endocrinology and Infertility Beth Israel Deaconess Medical Center 330 Brookline Avenue Boston, MA 02215, USA b Department of Obstetrics and Gynecology Harvard Medical School Boston,….<\/p>\n","protected":false},"author":1,"featured_media":0,"parent":1283,"menu_order":0,"comment_status":"open","ping_status":"open","template":"","meta":{"_bbp_topic_count":0,"_bbp_reply_count":0,"_bbp_total_topic_count":0,"_bbp_total_reply_count":0,"_bbp_voice_count":0,"_bbp_anonymous_reply_count":0,"_bbp_topic_count_hidden":0,"_bbp_reply_count_hidden":0,"_bbp_forum_subforum_count":0,"footnotes":""},"class_list":["post-1285","page","type-page","status-publish","hentry"],"_links":{"self":[{"href":"https:\/\/jacobimed.org\/old\/wp-json\/wp\/v2\/pages\/1285","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/jacobimed.org\/old\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/jacobimed.org\/old\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/jacobimed.org\/old\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/jacobimed.org\/old\/wp-json\/wp\/v2\/comments?post=1285"}],"version-history":[{"count":1,"href":"https:\/\/jacobimed.org\/old\/wp-json\/wp\/v2\/pages\/1285\/revisions"}],"predecessor-version":[{"id":1287,"href":"https:\/\/jacobimed.org\/old\/wp-json\/wp\/v2\/pages\/1285\/revisions\/1287"}],"up":[{"embeddable":true,"href":"https:\/\/jacobimed.org\/old\/wp-json\/wp\/v2\/pages\/1283"}],"wp:attachment":[{"href":"https:\/\/jacobimed.org\/old\/wp-json\/wp\/v2\/media?parent=1285"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}