Amenorrhea



Amenorrhea


Karen S. Vargo



The evaluation of amenorrhea in the adolescent requires a basic understanding of pubertal development, including the role of the hypothalamic-pituatary-ovarian (HPO) axis and its effect on the menstrual cycle. The differential diagnosis for primary and secondary amenorrhea are very similar except for a few genetic conditions that only cause primary amenorrhea.

Both primary and secondary amenorrhea can be assessed in a similar manner. Begin with a complete history and physical examination, followed by a step-by-step laboratory evaluation. If a methodical approach is utilized, the pediatrician can diagnose and manage most cases of amenorrhea. The practitioner should be sensitive to the effect amenorrhea can have on an adolescent’s body image and sexual identity.


DEFINITION OF AMENORRHEA

Primary amenorrhea is defined as:



  • Absence of menarche by the age of 15 years in the presence of otherwise normal growth and development


  • Absence of menarche and other signs of puberty, such as the development of breasts and pubic hair by the age of 13 years


  • Failure of menarche to occur within 5 years after the beginning of breast development if that occurs before age 10 years Secondary amenorrhea is defined as:


  • The absence of menses for longer than 3 months in a female patient with well-established menstruation


PHYSIOLOGY OF THE MENSTRUAL CYCLE

The HPO axis is directly responsible for regulating the menstrual cycle (Fig. 46.1). Gonadotropin-releasing hormone (GnRH) from the hypothalamus stimulates the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the pituitary. FSH and LH influence the ovarian production of estrogen and progesterone, which in turn have both a positive and negative feedback effect on the pituitary and the hypothalamus.


PHASES OF THE MENSTRUAL CYCLE

The menstrual cycle can be broken down into three phases (Fig. 46.2).


Follicular Phase

During the menses, low ovarian levels of estrogen stimulate the production of FSH. Final maturation of the follicle occurs under the stimulation of FSH. As the ovarian production of estrogen increases, the rising estrogen levels have a negative effect on FSH and a positive effect on LH. During the second half of this phase, estrogen stimulates growth of the endometrium.


Ovulatory Phase

The surge in LH secondary to positive estrogen feedback results in ovulation. As LH levels peak, estrogen levels fall.


Luteal Phase

This phase corresponds to the lifespan of the corpus luteum, which secretes progesterone and estrogen. Under the influence of these hormones, the endometrium becomes thicker and more vascular. Plasma levels of LH and FSH decline. If fertilization does not occur, the corpus luteum involutes within 14 days and estrogen and progesterone levels fall. With a fall in the levels of these hormones, the endometrium becomes necrotic and sloughs off in the process known as menstruation.







Figure 46.1 The hypothalamic-pituitary-ovarian axis. FSH, folliclestimulating hormone; GnRH, gonadotropin-releasing hormone; LH, luteinizing hormone.


MENARCHE AND THE ADOLESCENT MENSTRUAL CYCLE

Menarche occurs at a mean age of 12.5 years, with a range of 9 to 16 years. In most cases it occurs 1 year after the peak growth velocity and 2 years after the development of breast buds. By menarche, most girls have completed 75% of their pubertal development and achieved 90% of their growth potential. Early menstrual cycles are anovulatory. Ovulation usually begins within 1 to 2 years after menarche and reflects synchronization and maturation of the HPO axis. A normal menstrual period lasts from 2 to 7 days, with an average blood loss between 30 and 40 mL. Cycle lengths can vary between 21 to 45 days but are usually constant for a given individual.


ETIOLOGY OF AMENORRHEA

In considering the etiology of amenorrhea (Table 46.1), it is helpful to think about where along the HPO axis the problem exists. Try to differentiate a central problem at the level of the hypothalamus or pituitary from an ovarian problem or an end-organ problem. The classification of hypogonadotropic hypogonadism refers to low FSH and LH levels seen in conditions affecting the hypothalmus and the pituatary. Hypergonadotropic hypogonadism refers to to high FSH and LH levels seen in conditions affecting the ovary. In eugonadotropic conditions FSH and LH levels are normal.






Figure 46.2 Phases of the menstrual cycle. FSH, follicle-stimulating hormone; LH, luteinizing hormone.


Hypothalamic Disorders

Any condition associated with a deficiency of GnRH can cause amenorrhea. Constitutional delay of puberty is a common etiology of primary amenorrhea. This condition may be associated with short stature and a family history of delayed puberty or delayed menarche in an older sibling or parent. Other conditions that cause GnRH deficiency include hypothalamic tumors, isolated GnRH insufficiency, and Kallmann syndrome (GnRH deficiency and anosmia). Any type of chronic disease, such as inflammatory bowel disease, cystic fibrosis, systemic lupus erythematosus, and diabetes; nutritional problems (e.g., anorexia, bulimia, obesity), rigorous exercise, stress, and substance abuse can also result in GnRH deficiency.


Pituitary Disorders

Pituitary disorders that can cause amenorrhea include tumors such as prolactinomas and craniopharyngiomas. Other causes are idiopathic hypopituitarism and a history of central nervous system infection.









TABLE 46.1 ETIOLOGY OF AMENORRHEA






































































































































Hypothalamic disorders



Constitutional delay of puberty



Tumors



Isolated insufficiency of gonadotropin-releasing hormone



Kallmann syndrome


Chronic disease



Inflammatory bowel disease



Cystic fibrosis



Systemic lupus erythematosis



Diabetes


Nutritional problems



Anorexia



Bulimia



Obesity


Rigorous exercise: ballet, gymnastics, long-distance running



Stress



Substance abuse: opiates, heroin, phenothiazines


Pituitary disorders



Prolactinoma



Craniopharyngioma



Idiopathic hypopituitarism


Central nervous system infection



Ovarian disorders



Turner syndrome (45,X0)



Gonadal dysgenesis (46,XX)



Polycystic ovary syndrome



Ovarian failure




Infection, radiation, chemotherapy




Autoimmune disease




Idiopathic premature ovarian failure


Structural or end-organ defects



Genital tract obstruction



Imperforate hymen



Transverse vaginal septum



Asherman syndrome: ablation of uterine lining secondary to trauma or infection.



Mullerian agenesis (46,XX): partial or total vaginal agenesis



Androgen insensitivity syndrome (46,XY)


Other causes



Pregnancy



Hormonal contraception



Endocrinopathies



Diabetes mellitus



Thyroid disease: hyperfunction or hypofunction



Adrenal disease



Ovarian Disorders

Turner syndrome is one of the most common chromosomal disorders in humans and one of the most frequent causes of primary amenorrhea. It is characterized by a 45,XO karyotype, although up to 50% of affected persons may exhibit mosaicism (46,XX/45,XO). Some of the stigmata of Turner syndrome include short stature, webbed neck, shield chest, and streak ovaries.

Female gonadal dysgenesis is characterized by a 46,XX karyotype and streak ovaries.

Gonadal dysgenesis with a variety of other abnormal karyotypes such as XY or XXY may also occur. They are a rare cause of amenorrhea. Other ovarian conditions that result in amenorrhea include polycystic ovary syndrome and ovarian failure secondary to infection, radiation, chemotherapy, autoimmune disease, or an idiopathic cause.


Structural or End-organ Defects

Any sort of genital tract obstruction can result in amenorrhea. An imperforate hymen or a transverse vaginal septum will often present with cyclic pain resulting from the accumualtion of blood behind the obstruction. Asherman syndrome is iatrogenic scarring of the uterine lining, usually secondary to trauma sustained during a dilation and curettage procedure or infection. Mullerian agenesis refers to partial or complete agenesis of the vagina. The uterus and fallopian tubes are usually absent or rudimentary and the karyotype is 46,XX. In complete androgen insensitivity syndrome, the individual appears phenotypically female with normal female breasts and external genitalia. However, the vagina ends in a blind pouch and pubic hair is absent or sparse. The karyotye is 46,XY and inguinal or intra-abdominal testes are present. Because of the risk of malignancy, the testes should be removed after breast development and adult stature have been achieved.


Other Causes

Pregnancy should always be considered in both primary and secondary amenorrhea. Other considerations include hormonal contraception and endocrinopathies such as diabetes, thyroid disease, and adrenal disease.


EVALUATION OF AMENORRHEA


History

Begin the evaluation of primary and secondary amenorrhea with a detailed history of the patient’s growth and development (Table 46.2). In the case of primary amenorrhea, specifically inquire about the age at thelarche (development of breast buds), adrenarche (growth of pubic hair), and the growth spurt. Important details of the menstrual history include the age at menarche, frequency and duration of menses, presence of dysmenorrhea, and breast changes associated with menses. Inquire about a history of chronic disease or a serious childhood illness, such as a central nervous system infection. The family history should include the ages of puberty and menarche for parents and siblings. Inquire about a history of psychiatric illness, environmental stress, medications, and drug abuse. Has the patient experienced a recent weight change? Take a detailed dietary history and ask about body image to explore the possibility of an eating disorder. Extreme exercise habits and participation in
competitive sports can cause amenorrhea in the female athlete. Obtain a sexual history regarding past and present sexual activity. Inquire about signs of androgen excess or virilization, such as acne and hirsutism. Also ask about galactorrhea associated with conditions causing hyperprolactinemia.

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Jul 5, 2016 | Posted by in CRITICAL CARE | Comments Off on Amenorrhea

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