[3] 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.
[3] It is often caused by hormonal disturbances from the hypothalamus and the pituitary gland, premature menopause, intrauterine scar formation, or eating disorders.
[8] FSH and LH then act on the ovaries to stimulate the production of estrogen and progesterone which, respectively, control the proliferative and secretary phases of the menstrual cycle.
[11] 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.
[13][14] 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.
[22][23] Constitutional delay of puberty is a diagnosis of exclusion that is made when the workup for primary amenorrhea does not reveal another cause.
[26] Lactational amenorrhea is due to the presence of elevated prolactin and low levels of LH, which suppress ovarian hormone secretion.
[3] Any pathology in the hypothalamus or pituitary can alter the way this feedback mechanism works and can cause secondary amenorrhea.
[33] Although the exact cause remains unknown, it is hypothesized that increased levels of circulating androgens is what results in secondary amenorrhea.
[35] Functional hypothalamic amenorrhoea (FHA) can be caused by stress, weight loss, or excessive exercise.
[37] Relative energy deficiency in sport, also known as the female athlete triad, is when a woman experiences amenorrhoea, disordered eating, and osteoporosis.
[38] Elevated concentrations of ghrelin alter the amplitude of GnRH pulses, which causes diminished pituitary release of LH and follicle-stimulating hormone (FSH).
Patients who stop using combined oral contraceptive pills (COCP) may experience secondary amenorrhoea as a withdrawal symptom.
[46] Research suggests that anti-psychotic medications affect levels of prolactin, insulin, FSH, LH, and testosterone.
[46] Recent research suggests that adding a dosage of Metformin to an anti-psychotic drug regimen can restore menstruation.
[15] Since the pathogenesis of POI involves the depletion of ovarian reserve, restoration of menstrual cycles typically does not occur in this form of secondary amenorrhea.
[15] Primary amenorrhoea can be diagnosed in female children by age 14 if no secondary sex characteristics, such as enlarged breasts and body hair, are present.
[17] Evaluation of primary amenorrhea begins with a pregnancy test, prolactin, FSH, LH, and TSH levels.
[13] Abnormal TSH levels prompt evaluation for hyper- and hypo-thyroidism with additional thyroid function tests.
[13] If a uterus is not present on ultrasound, karyotype analysis and testosterone levels are obtained to assess for MRKH or androgen insensitivity syndrome.
[13] Elevated levels of FSH and LH suggest primary ovarian insufficiency, typically due to Turner syndrome.
[13] Normal or low levels of FSH and LH prompts further evaluation with patient history and the physical exam.
[13] Finally, a history of gynecologic procedures should lead to evaluation of Asherman syndrome with a hysteroscopy or progesterone withdrawal bleeding test.
[54] However, patients are frequently prescribed growth hormone therapy and estrogen supplementation to achieve taller stature and prevent osteoporosis.
Functional hypothalamic amenorrhoea is typically treated by weight gain through increased calorie intake and decreased expenditure.
[7] Multidisciplinary treatment with monitoring from a physician, dietitian, and mental health counselor is recommended, along with support from family, friends, and coaches.
[34] Weight loss and exercise have been associated with a return of ovulation in patients with PCOS due to normalization of androgen levels.
[34] Although the exact mechanism still remains unknown, it is hypothesized that this is due to metformin's ability to increase the body's sensitivity to insulin.