Pathophysiology
Summary
Amenorrhea can be categorized as primary or secondary. Primary amenorrhea is defined as the absence of menses by age 15, or by age 13 if there are no secondary sex characteristics like breast development or pubic hair.
Congenital GnRH deficiency is a form of primary amenorrhea that causes reduced secretion of FSH & LH by the anterior pituitary and a consequent decreased secretion of estrogen by the ovaries. A subtype of this condition is Kallmann syndrome, which pairs congenital GnRH deficiency with anosmia, an absence of the sense of smell. The presentation includes an absence of secondary sex characteristics due to a total lack of estrogen.
Ovarian dysfunction can also lead to primary amenorrhea. It is marked by decreased estrogen levels and increased levels of FSH and LH due to reduced negative feedback mechanisms on the hypothalamus and pituitary gland. A specific case of ovarian dysfunction is Turner syndrome, defined by a 45 XO genotype. In Turner syndrome, ovarian follicles are replaced by fibrous connective tissue, known as streak gonads, leading to atrophic ovaries and a lack of estrogen production. Both Congenital GnRH deficiency and Turner syndrome result in a lack of secondary sex characteristics.
Müllerian agenesis, also known as MRKH syndrome, causes primary amenorrhea due to agenesis of the female upper genital tract. Normally, Müllerian ducts develop into the fallopian tubes, uterus, and upper vagina. Müllerian agenesis presents with amenorrhea but normal development of secondary sex characteristics, as the ovaries are still functional.
Imperforate hymen also results in primary amenorrhea, and occurs when the central hymen fails to degenerate, leading to obstruction of outflow from the vagina. This manifests as cyclic abdominal or pelvic pain due to pooling of menstrual blood. Like Müllerian agenesis, they have normal development of secondary sex characteristics since the ovaries are intact.
Secondary amenorrhea is characterized by the cessation of menstrual cycles in those who previously had regular menses. The most prevalent cause of secondary amenorrhea is pregnancy. However, hormonal and structural abnormalities can also contribute.
Acquired GnRH deficiency can occur in cases of extreme exercise or severe caloric restriction as in anorexia nervosa. This condition results in reduced secretion of FSH & LH by the anterior pituitary and subsequently decreased estrogen production by the ovaries.
Hyperprolactinemia can also cause secondary amenorrhea, as increased prolactin levels inhibit GnRH secretion by the hypothalamus. Prolactinomas are the most common cause of hyperprolactinemia, and can manifest as galactorrhea due to elevated prolactin levels. Drugs that inhibit dopamine like antipsychotics can also induce hyperprolactinemia and consequent amenorrhea.
Hypothalamic and pituitary dysfunction can also cause secondary amenorrhea. Structural factors include surgical removal of the ovaries, which leads to increased FSH and LH levels due to reduced negative feedback mechanisms on the hypothalamus and pituitary gland.
Menopause, defined as the absence of menses for >12 months without other underlying pathology, is also considered secondary amenorrhea. Physiological menopause occurs due to depletion of ovarian follicles, leading to decreased estrogen and elevated FSH. The menopausal transition, or perimenopause, may manifest with symptoms such as hot flashes, night sweats, and vaginal dryness. Additionally, menopause leads to decreased bone density due to the absence of estrogen's inhibitory effect on osteoclast-mediated bone resorption.
Secondary amenorrhea can also arise in primary ovarian insufficiency, which is characterized by menopausal symptoms prior to age 40, irregular menstrual cycles, and elevated FSH levels. Asherman syndrome also presents with secondary amenorrhea due to endometrial scarring that hinders the normal buildup and shedding of the endometrial lining and can occur due to repeated endometrial infections or surgical interventions on the uterus.
Lesson Outline
Don't stop here!
Get access to 155 more Pathophysiology lessons & 13 more medical school learning courses with one subscription!
FAQs
Amenorrhea refers to the absence of menstrual periods and is classified into two types: primary and secondary. Primary amenorrhea occurs when an individual has not started menstruating by age 15, or by age 13 if no secondary sexual characteristics are present. Secondary amenorrhea is defined as the cessation of menstrual periods in someone who previously had regular cycles. Clinical manifestations can vary, ranging from the absence of secondary sexual characteristics to symptoms associated with low estrogen levels, such as hot flashes, vaginal dryness, and decreased bone density.
Primary amenorrhea can arise from several conditions, including congenital GnRH deficiency, ovarian dysfunction, Turner syndrome, and Mullerian agenesis. Congenital GnRH deficiency, including variants like Kallmann syndrome, leads to reduced secretion of FSH and LH by the pituitary gland, resulting in low estrogen levels. In Turner syndrome, ovarian follicles are replaced by fibrous tissue, leading to a lack of estrogen production. Mullerian agenesis, also known as MRKH syndrome, involves the absence of the upper female genital tract, including the fallopian tubes, uterus, and upper vagina, resulting in primary amenorrhea.
GnRH deficiencies can lead to amenorrhea by causing a decrease in the secretion of FSH and LH by anterior pituitary, which subsequently reduces estrogen production by the ovaries. Congenital GnRH deficiency is a form of primary amenorrhea that is present from birth, and often manifests as an absence of secondary sexual characteristics. Acquired GnRH deficiency, which can lead to secondary amenorrhea, may be triggered by factors such as excessive exercise or severe caloric restriction, as seen in conditions like anorexia nervosa.
Secondary amenorrhea may arise from a variety of factors such as pregnancy, hyperprolactinemia, and menopause. Dysfunction of the hypothalamus and pituitary gland can also contribute to this condition. Additionally, surgical ovarian removal and specific conditions like Asherman syndrome, characterized by endometrial scarring, may lead to the cessation of menstrual cycles. In Asherman syndrome, scar tissue interferes with the normal growth and shedding of the endometrial lining, resulting in an absence of menstruation.
Hyperprolactinemia can lead to secondary amenorrhea by inhibiting the secretion of GnRH by the hypothalamus. This condition is often caused by prolactinomas, benign tumors that secrete prolactin, resulting in elevated levels of this hormone and potentially leading to lactation. Certain antipsychotic medications with dopamine receptor antagonist effects can also induce hyperprolactinemia by inhibiting the suppression of prolactin secretion by the pituitary gland.
