Amenorrhea can be sub grouped as primary or secondary. Primary amenorrhea is either the absence of periods by the age of 14 in the absence of growth or development of secondary sexual characteristics (presence of axillary or pubic hair, breast development or growth). Or, absence of periods by the age of 16 regardless of growth or development of secondary sexual characteristics. Secondary amenorrhea is defined as absence of periods for 6 months in a woman previously menstruating regularly.
Primary Amenorrhea: Clinicians find it useful to classify the causes of primary amenorrhea based on the presence of secondary sexual characteristics (breast) and female internal genitalia (uterus). The findings on physical examination can alert the clinician of possible causes and indicate which laboratory tests should be performed.
All women in this group experience a failure of ovarian estrogen production as a result of hypothalamic-pituitary dysfunction or gonadal disorder. The causes and prognoses of these disorders differ significantly and establishment of the exact diagnosis is important.
A) Gonadal Failure: Genetic abnormalities are the most common cause of primary amenorrhea. Gonadal failure most often derives from a chromosomal aberration that results in partial or total deletion of the X chromosome. (Two X chromosomes are necessary for normal development). In some cases, other chromosome structure abnormalities may be the cause. Certain enzyme deficiencies may also present with the same clinical picture. These patients require using donor eggs and IVF to conceive, but can carry the pregnancy to term and deliver.
B) Hypothalamic Failure: Insufficient gonadotropin releasing hormone (GnRH) synthesis or secretion, and some types of anatomic defects of the hypothalamic area, can result in hypothalamic failure and primary amenorrhea. Lack of GnRH secretion will result in decreased levels of FSH/LH hormone levels and failure of ovarian follicle development. As a result of this pathology, low estrogen levels and primary amenorrhea will be observed. These patients can conceive with gonadotropin treatment to stimulate ovarian follicle growth. Administration of GnRH hormone can also be effective for fertility.
C) Pituitary Failure: Gonadotropin deficiency (FSH and LH), certain tumors, infectious causes and prepubertal hypothyroidism can result in primary amenorrhea. The treatment should focus on the cause, and administration of gonadotropins can result in follicle/egg development and result in pregnancy.
There are two main types of abnormalities within this group: androgen insensitivity (testicular feminization) and congenital absence of the uterus. The former is characterized by an XY genotype and female appearance. These individuals are reared as females and need removal of gonads (XY) after puberty. They can neither produce eggs due to absence of the ovaries, nor carry the pregnancy because of an absent uterus. The latter involves the absence of the uterus and presence of XX genotype and female appearance. These patients have ovaries and can develop ovarian follicles and eggs. They require in-vitro fertilization and embryo transfer (IVF-ET) and need a gestational surrogate to carry the pregnancy because of the absence of the uterus.
This group of patients with primary amenorrhea is extremely rare and may have XY karyotype. These patients neither have ovaries nor uterus, and lack the secretion of sex steroids such as estrogen and progesterone.
This group constitutes one third of patients with primary amenorrhea. Most common causes of amenorrhea in this group are high prolactin levels, polycystic ovary syndrome, hypothalamic-pituitary dysfunction and various degrees of ovarian failure. Treatment of infertility in these groups of patients is directed towards the cause of the amenorrhea and the prognosis is generally good.