This document provides information on disorders of adolescent sexual maturation. It defines adolescent sexual disorders and describes the types, including accelerated sexual maturation (precocious puberty) which can be gonadotropin dependent or independent. Gonadotropin dependent precocious puberty is the result of premature activation of the hypothalamus and pituitary glands. Gonadotropin independent precocious puberty is caused by conditions like congenital adrenal hyperplasia or tumors. Incomplete forms of pubertal development like premature thelarche and pubarche are also discussed.

1. Valley View University
School of Nursing and Midwifery
Department of Midwifery
Gynaecology - Unit XII
Disorders of Adolescent sexual maturation
By
Doris Grace Kpongboe

2. Objectives of the lecture
At the end of the lecture students will be able to:
1. Define adolescent sexual disorder
2. Describe the types of adolescent sexual disorders
3. Explain the aetiology of adolescent sexual disorders
4. Describe the management of adolescent sexual disorders

3. Introduction
• In puberty, there is sexual maturity that makes the individual sexually
mature and thus capable of reproduction.
• This results from the influence of the hormones from the
hypothalamus and the pituitary glands.
• There is thus development of the breast, cornification of the vaginal
mucosa and growth of genital hair.
• These usually precede uterine bleeding by about 2 years.

4. Introduction
• The normal sequence is often shown with:
- Accelerated growth
- Early oestrogen effects of the genitalia which usually occurs firs
- The obvious signs of early puberty are the enlargement of the breast
which initially may be unilateral
• Pubic and axillary hair may appear before, at the same time or well
after the development of the breast tissues
• The vaginal mucosa in the pre- pubertal period has a deep red colour
but take on a moist –paste-pink appearance as it is exposed to the
increased effect of oestrogen

5. Introduction
• Menstruation is late event and it come on 2-3 years after the breast
enlargement.
• Girls of African American descent show secondary sexual features earlier
than North American girls.
• The North America girls have breast budding (Thelarche) between 7 and 11
years followed by growth of pubic hair (Pubarche)
• This is followed with marked increase in growth referred to as adolescent
growth spurts.
• In the USA averagely the first menstrual period occurs at 12.8 years with
regular ovulatory cycle 20 month later to mark the end of the pubertal
changes

6. Accelerated sexual maturation (Sexual
Precocity)
• This is the onset of sexual maturation at any age that is 2.5 standard
deviation (SD) earlier than the normal age for the population.
• There are two (2) forms which may be classified as: -
- Gonadotropin Releasing Hormone (GnRH) dependent precocious
puberty (or true precocious puberty)
- Gonadotropin independent precocious puberty (or Pseudo
precocious puberty)

7. GnRH-dependent Precocious Puberty
• This is normal pubertal development that occurs at an early age.
• It is the result of premature activation of the hypothalamus and the
pituitary glands followed by the secretion of the gonadotropin.
• This is turn stimulates the gonads to produce steroid hormones and
subsequently pubertal changes occurs.
• GnRH –dependent precocious puberty is seen more frequently in
girls than in boys.
• The course is unclear and has been referred to as Central Precocious
Puberty (CPP).

8. GnRH-dependent Precocious Puberty
• Most girls suspected of CPP are usually heathy children whose pubert
maturation begins early (between 6 and 8 years).
• Central Nervous System (CNS) imaging studies show no structural
abnormalities usually.
• Occasionally however, such CNS abnormalities as hypothalamic
haematomas, optic gliomas, neurifibromas and other CNS neoplasma
may be identified.
• Also prolonged exercise therapy with exogenous sex steroids may
accelerate the maturation of the hypothalamus and pituitary axis
resulting in precocious puberty.

9. Diagnosis
• History
• Physical examination
• X’ray
• Laboratory tests

10. GnRH-independent Precocious Puberty
(Pseudo Precocious Puberty)
• Here, there is appearance of precocious Puberty but the Presence of
sex steroids is independent of the release of pituitary gonadotropin
• The causes include: -
- Congenital adrenal hyperplasia
- Tumours that secrete human chronic gonadotropin
- Tumours of the adrenal glands
- Tumours of the gonads
- Macune-Albright Syndrome (MAS)
- Exposure to exogenous sex steroids hormones

11. NOTE THAT:
• Macune Albright syndrome is a disorder that affects the bones, skin
and several hormone producing (endocrine) tissues.
• Affected people develop areas of scar-like (fibrous) tissue in their
bones known as polyostotic fibrous dysplasia

12. Endogenous oestrogen
• The ovary in the newborn female contains 1-2 million premodial follicles.
• These undergo atresia during childhood without producing much
Oestrogen.
• However, the following may occur:
- Long follicular cyst which are capable of producing oestrogen may occur
which can result in early feminization.
- Benign tumours of the ovary such as teratoma , cystadenoma may produce
oestrogen or may induce the surrounding ovarian tissues to produce
steroids.
- Thus the circulating sex steroid cause the development of secondary sexual
development.

13. PS:
• The sex steroids are oestrogen in the females or testosterone in the
male
• These are steroids may come either from the adrenal gland or the
gonads.
• This secretion is independent of the hypothalamus and pituitary
• Sex steroids may also be ingested or be absorbed from exogenous
sources
• Granolosa Cell tumours which are capable of producing oestrogen
may rarely cause pre-pubertal feminization

14. PS
• Granolosa Cell tumours which are capable of producing oestrogen
may rarely cause pre-pubertal feminization
• Other rare tumours of extra gonadal origin that may also produce
oestrogen includes:
- Adrenal adenomas
- Hepatomas
oHere the neoplasm secretes GnRH which inturn stimulate the gonads
to produce sex hormones

15. Exogenous Oestrogens
• This is the injection of oestrogen or prolonged use of creams
containing oestrogens.
• It is however an uncommon cause of early feminization.
• If it occurs prompt decontinuation is indicated

16. McCune- Albright Syndrome (MAS)
• This is a condition that consists of at least 2 features of a triad namely:
- polyostotic fibrous dysplasia
- Café-out-lait skin pigmentation
- Autonomous endocrine hyperfunctions
- The most common form is GnRH secretion and subsequent precocious
puberty.
• Although in MAS changes in the ovary, bone and skin tissues are common.
Other endocrine and non-endocrine tissues may also be affected.
• The others include the adrenal thyroid, pituitary liver and heart.
• The fibrous dysplasia seen in children affected with MAS are mostly
common seen in long bones, ribs and skills.

17. McCune- Albright Syndrome (MAS)
• The lesion may range from a small asymptomatic area to are large
lesion that can result in pathogenic fractures.
• The café-au-lait spots are large malanotic maculus with irregular
outlines, described as coast of marine.
- These are hyper-pigmented lesions that may vary in colour from light
brown to dark brown
PS:
MAS is caused by a post-zygotic somatic mutation in the gene coding.

18. Cause of MAS
• Cause is unknown but a primary ovarian abnormality and premature
oestrogen production has been suggested

19. Manifestations of MAS
• Affected children with MAS show at a younger age than those with
idiopathic precocious puberty.
• Vaginal bleeding occurs early.
• It is the sign of puberty in most cases
• There is skin pigmentation
• There is demonstration of bone lesions or fractures

20. Diagnosis
• There is made on the basis of:
- Skin pigmentation
- Bone lesions or pathological fractures

21. Incomplete forms of pubertal development
• In this situation only one (1) sign of pubertal development is present (ie
either breast development, public hair or menstruation)
• Premature thelarche and premature puberache are more common
conditions than true precocious puberty
• These are two (2) benign normal forms that resembles precocious puberty.
- These are however non-progressive or may progress very slowly.
- It is said to be possibly result from transient elevations of the levels of
circulating steroid hormones or from extreme sensitivity of the end organ
(eg the breast tissue) to the pre-pubertal levels of sex hormones.
• Such isolated development may represent the initial sign of precocious
puberty.
• Such patients should be re-evaluated at regular intervals.

22. Premature thelarche
• Premature thelarche is the isolated development of breast tissue prior to 8
years of age.
• It may affect 1 or both breasts.
• The patient has to go through a thorough history, physical examination and
growth curve review as this can help distinguish this normal variant from
true sexual precocity.
• Examination will reveal that the somatic growth pattern is not accelerated,
bone age is not advanced and smear of the vaginal secretions fails to show
oestrogen effect.
• The diagnosis is then made by exclusion of other disorders
• Occasionally, premature thelarche occurs when the child is exposed to
exogenous oestrogen (say in the food chain – as seen an epidemic of
premature thelarche in Pueto Rico in the 1970s)

23. Premature pubarche
• Previously, premature pubarche was defined as the appearance of
public or axillary hair prior to 8 years without other signs of
precocious puberty.
• New guidelines however, suggest that this presentation should be
considered unless it is noted before 7 years in white girls and before 6
years in black girls.
• Such hair growth may be idiopathic and of no clinical significance.
• Premature pubarche is thought to result from an earlier than usual
increase in the secretion of androgens by the adrenal glands.

24. PS
• The regulation of the adrenal androgens secretion is distinct from
gonadal secretion; therefore, early appearance of public hair does not
correlate with true precocious puberty.
• This therefore is not a cause for concern.
 A diagnosis is made only when thorough examination of the adrenal
and gonadal functions and the assessment of androgen production
fail to defect an abnormality.
• Signs of severe androgen excess (clitoral enlargement, growth
acceleration, acne) should prompt further investigation for rare
virilizing tumour (Leydig cell tumour) or a variant form of congenital
adrenal hyperplasia.

25. Premature menache
• This is the appearance of cyclic vaginal bleeding in children in the
absence of other sign of secondary sexual development.
• The cause is unknown.
• It may however have related to increased end-organ sensitivity of the
endometrium to how pre-pubertal levels of oestrogens.
• Alternatively, bleeding may be related transient elevation of
oestrogen due to premature follicular development.

26. Premature menache
• These patients have estradiol levels in the cytologic smear of vaginal
secretions indicate lack of oestrogenic stimulation.
• The diagnosis is made after investigation of other causes of vaginal
bleeding and it confirmed when the cyclic nature of bleeding
becomes obvious

27. Prognosis
• This is usually good as:
- Adult height is not compromised
- Menstrual pattern is normal
- Fertility potential remains un impaired

28. Evaluation of patients with precocious
puberty
• Age of onset
• Duration
• Progressive sign (very important)
• Family history and review of the system shows: -
 Generally, the charges result from enhancement of general growth
which coincides with the onset of oestrogen stimulated change
- There is accelerated growth velocity with tall stature for age
- There is advanced skeletal maturation

29. Evaluation of patients with precocious
puberty
Skin exhibits changes including androgen –dependent effect including
acne and adult –type body odour
Breast development is at Tanner stage II with the areola having
broadened darkened appearance
 Genital changes reflect: -
- Oestrogen induced thickening of genital tissue
- Increased vaginal secretion may result in Leukorrhoea
- Dark coarse pubic hair may be present

30. Diagnosis
1. Estimation of serum luteinizing hormone, follicle stimulating hormone
and oestradiol level
2. GnRH stimulation test, in patient with GnRH- development precocious
puberty, the results are in normal ranges.
3. Diagnostic images to documents skeletal age and the absence of gonadal
of CNS lesions
4. Imaging of uterine size shows the length of time magnitude of oestrogen
exposure.
5. Ovarian cyst and tumours may also be visible on scan.
6. Brain MRI is indicated in patient with sexual precocity or with
neurological signs.

31. Treatment
• Administration of GnRH analogue in the those with GnRH- dependent
precocious puberty.
• This reduces gonadotrophin and sex steroids to pre-pubertal levels.

32. Delayed sexual maturation
• This is the absence of normal pubertal events at an age 2.5 SD later
than the mean.
- The absence of thelarche by age 13 years. OR
- The absence menarche by age 15 years.
PS
• Some degree of sexual maturation occurs in patient with gonadal
dysgenesis therefore patient who presents with a delay orderly
progression of pubertal development must undergo investigation

33. Classification of patients with delayed sexual
maturation
• The classifications include:
- Delay menarche with adequate secondary sexual development
- Most patient have well-formed female configuration with adequately
developed breasts
- They may suffer from inappropriate hypothermic- pituitary –ovarian
feedback mechanism which results in an ovulation and androgen
excess
- Primary amenorrhea may persist with a progestin is given

34. Classification of patients with delayed sexual
maturation
- The common defect is congenital absence of the uterus and vagina
- Other abnormalities include the obstructer abnormalities such as
imperforate hymen transvaginal septa, agenesis of the cervix
- The complete form of androgen insensitivity is also associated with
amenorrhea and complete breast development.
- Pubic and axillary hair is scanty or pouch is present

35. Investigations
• Patient should be monitored for continual menstrual shedding with
the administration of progestin
• MRI to establish congenital abnormalities
• Evaluation should be made for adrenal hyperplasia and polycystic
ovarian disease especially those with persistent menstrual
abnormality
• Evaluate for possible pregnancy

36. Management
• Administration of progestin every other month to prevent
endometrial hyperplasia
• Oral contraceptive rather than cyclic progestin for sexually active girls.
• Surgical removal of the gonads and reconstruction of the vagina

37. Delayed puberty with inadequate or absent
secondary sexual development Hypothalamic-
pituitary dysfunction
• Delayed puberty secondary may be due to lack of maturation or
function of the hypothalamus and pituitary
• Here, the onset of puberty depends on a re-defined stage of maturity
that is reflected in skeletal age.
• It has been shown that about 2.5% of normal adolescent will develop
later than the age defined as normal.
• This group is described as ‘late bloomers’’ or having constitutional
growth delay.