Amenorrhea or amenorrhoea is the absence of a menstrual period in a female organism which has reached reproductive age. Physiological states of amenorrhea are most commonly seen during pregnancy and lactation (breastfeeding). Primary amenorrhea is defined as an absence of secondary sexual characteristics by age 13 with no menarche or normal secondary sexual characteristics but no menarche by 15 years of age. It may be caused by developmental problems, such as the congenital absence of the uterus, failure of the ovary to receive or maintain egg cells, or delay in pubertal development. Secondary amenorrhea, ceasing of menstrual cycles after menarche, is defined as the absence of menses for three months in a woman with previously normal menstruation, or six months for women with a history of oligomenorrhea.
Physiologically, menstruation is controlled by the release of gonadotropin-releasing hormone (GnRH) from the hypothalamus. Similarly, thyroid hormone also affects the menstrual cycle.
Primary amenorrhea
Primary amenorrhea is the absence of menstruation in a woman by the age of 16. Females who have not reached menarche at 14 and who have no signs of secondary sexual characteristics (thelarche or pubarche) are also considered to have primary amenorrhea. Examples of amenorrhea include constitutional delay of puberty, Turner syndrome, and Mayer–Rokitansky–Küster–Hauser (MRKH) syndrome.
It produces the appearance of secondary sexual characteristics, which are the sprouting of pubic and armpit hair, development of the breasts, and a lack of definition in the female body structure, such as the waist and hips.
Secondary amenorrhea
Secondary amenorrhea is defined as the absence of menstruation for three months in a woman with a history of regular cyclic bleeding or six months in a woman with a history of irregular menstrual periods. Examples of secondary amenorrhea include hypothyroidism, hyperthyroidism, hyperprolactinemia, polycystic ovarian syndrome, primary ovarian insufficiency, and functional hypothalamic amenorrhea.
Causes
Primary amenorrhea
Turner syndrome
Turner syndrome, monosomy 45XO, is a genetic disorder characterized by a missing, or partially missing, X chromosome. Turner syndrome is associated with a wide spectrum of features that vary with each case. Most people with Turner syndrome experience ovarian insufficiency within the first few years of life, before menarche. The syndrome is characterized by Müllerian agenesis. In MRKH Syndrome, the Müllerian ducts develop abnormally and result in the absence of a uterus and cervix.
Constitutional delay of puberty
Constitutional delay of puberty is a diagnosis of exclusion that is made when the workup for primary amenorrhea does not reveal another cause. Constitutional delay of puberty is not due to a pathologic cause. It is considered a variant of the timeline of puberty. This may be due to genetics, as some cases of constitutional delay of puberty are familial. Lactational amenorrhea is due to the presence of elevated prolactin and low levels of LH, which suppress ovarian hormone secretion. Breastfeeding typically prolongs postpartum lactational amenorrhea, and the duration of amenorrhea varies depending on how often a woman breastfeeds. Due to this reason, breastfeeding has been advocated as a method of family planning, especially in developing countries where access to other methods of contraception may be limited.
Patients with hypothyroidism frequently present with changes in their menstrual cycle. Prolactin secreting pituitary adenomas cause amenorrhea due to the hyper-secretion of prolactin which inhibits FSH and LH release.
Polycystic ovary syndrome
Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting 4–8% of women worldwide. It is characterized by multiple cysts on the ovary, amenorrhea or oligomenorrhea, and increased androgens. PCOS may also be a cause of primary amenorrhea if androgen access is present prior to menarche. Functional hypothalamic amenorrhea (FHA) can be caused by stress, weight loss, or excessive exercise. Amenorrhea is often associated with anorexia nervosa and other eating disorders. Relative energy deficiency in sport, also known as the female athlete triad, is when a woman experiences amenorrhea, disordered eating, and osteoporosis. Weight loss can cause elevations in the hormone ghrelin which inhibits the hypothalamic-pituitary-ovarial axis. Low levels of the hormone leptin are also seen in females with low body weight. Like ghrelin, leptin signals energy balance and fat stores to the reproductive axis. The lack of menstruation usually begins shortly after beginning the medication and can take up to a year to resume after stopping its use. Extended cycle use of combined hormonal contraceptives also allow suppression of menstruation. Patients who stop using combined oral contraceptive pills (COCP) may experience secondary amenorrhea as a withdrawal symptom.
Anti-psychotic drugs, which are commonly used to treat schizophrenia, have been known to cause amenorrhea as well. Research suggests that anti-psychotic medications affect levels of prolactin, insulin, FSH, LH, and testosterone. Although the cause of POI can vary, it has been linked to chromosomal abnormalities, chemotherapy, and autoimmune conditions. If a uterus is present, LH and FSH levels are used to make a diagnosis.
Secondary amenorrhea
Secondary amenorrhea's most common and most easily diagnosable causes are pregnancy, thyroid disease, and hyperprolactinemia. A pregnancy test is a common first step for diagnosis. Headache, vomiting, and vision changes can be signs of a tumor and needs evaluation with MRI. Treatment not only focuses on restoring menstruation, if possible, but also preventing additional complications associated with the underlying cause of amenorrhea. However, patients are frequently prescribed growth hormone therapy and estrogen supplementation to achieve taller stature and prevent osteoporosis. Patients with constitutional delay of puberty may be monitored by an endocrinologist, but definitive treatment may not be needed as there will eventually be progression to normal puberty.
Secondary amenorrhea
Treatment for secondary amenorrhea varies greatly based on the root cause. Functional hypothalamic amenorrhea is typically treated by weight gain through increased calorie intake and decreased expenditure. Multidisciplinary treatment with monitoring from a physician, dietitian, and mental health counselor is recommended, along with support from family, friends, and coaches. For example, administration of thyroxine in patients with low thyroid levels restored normal menstruation in a majority of patients.