AMENORRHEA (Part One)
General
Amenorrhea is the absence of 3 (three) or more menstrual cycles (90 days or more). Amenorrhea is a normal sign in prepuberty, pregnant women, and postmenopausal women. In reproductive-age women, pregnancy is initially ruled out, and in its absence, an evaluation of a possible cause is performed.
Amenorrhea is classified into two main forms: primary and secondary
- Primary amenorrhea occurs when the menstrual cycle has not started by the age of 16 in the presence of normal pubertal development, normal growth, and secondary sexual characteristics.
- Secondary amenorrhea occurs when there is a lack of menstruation after menarche has occurred.
Physiopathology
The menstrual cycle develops as a result of normal coordination of the Hypothalamus-Pituitary-Ovarian axis. It occurs as a result of hormone production leading to the release of a matured egg from the ovary and preparation of the site for implantation if fertilization occurs. The menstrual cycle occurs when the released egg is not fertilized. As a result, there is shedding of the hypertrophied endometrium in the form of menstruation.
The menstrual cycle is divided into three main phases: follicular, ovarian, and luteal. Each phase involves a different secretion of hormones.
1 - Follicular Phase
In physiological terms, the first day of a menstrual cycle is considered the first day of menstruation. This phase continues until day 13 of the cycle. Since 2-3 days before menstruation, the levels of progesterone, estrogen, and inhibin decrease, the hypothalamus produces GnRH (gonadotropin-releasing hormone), which acts on the pituitary gland, which begins to increase the level of FSH (follicle-stimulating hormone). FSH is released into the bloodstream by the gland and acts on the granulosa cells of the follicle. FSH stimulates the aromatization of androgens into estradiol. The increase in estradiol and FSH results in an increase in FSH receptors in the follicles. The rise in LH receptors in granulosa cells of the dominant follicle occurs due to the combination of estradiol and FSH before ovulation. The increase in LH leads to the maturation and release of the dominant oocyte, and later to the luteinization of granulosa cells and the formation of the corpus luteum, which produces progesterone. Estradiol leads to the growth of the endometrial glands.
2 - Ovulatory Phase
Ovulation occurs approximately 10-12 hours after the peak of LH and 24-36 hours after the peak of estradiol. The increase in progesterone leads to an increase in the stretching of the follicular wall, an increase in enzymatic proteolytic activity, and the breakdown of collagen in the follicular wall. After the egg is released, the granulosa cells increase in size and turn yellow. The corpus luteum continues to vascularize and produces estrogen, progesterone, and androgens.
3 - Luteal Phase
The corpus luteum continues to produce progesterone, which acts on the endometrium and prepares it for implantation. This process is called endometrial decidualization. If conception occurs, luteal function is maintained until the placenta itself begins to produce hCG. Otherwise, if conception does not occur, the corpus luteum is not maintained, and menstruation occurs 14 days after ovulation.
Types of Amenorrhea
1 - Hypothalamic Amenorrhea
Hypothalamic dysfunction leads to a decrease or inhibition of GnRH production, which inhibits the production of FSH and LH by the pituitary gland, resulting in anovulation. Causes may include: severe eating disorders, increased physical activity, extreme stress, severe psychiatric disorders such as depression, hypothyroidism, hyperthyroidism, sarcoidosis, chronic severe disorders, idiopathic hypogonadotropic hypogonadism.
2 - Hypophyseal Amenorrhea
Deficiency of FSH and LH may result from a mutation in the GnRH receptor genes (rare). It is caused by hyperprolactinemia (most often due to prolactinoma), pituitary tumors that inhibit gonadotropin secretion, such as Cushing's Syndrome, pituitary tumors (craniopharyngioma and germinoma), brain injuries, cranial radiation, empty sella syndrome, pituitary infarctions, sarcoidosis, hemochromatosis.
3 - Ovarian Amenorrhea
Occurs in cases of gonadal dysgenesis (Turner syndrome), primary ovarian insufficiency, Polycystic Ovary Syndrome (PCOS).
4 - Amenorrhea from Anatomical and Structural Anomalies
The uterus and genital tracts must have normal development for a normal menstrual cycle. It accounts for 1/5 of the causes of amenorrhea. These include: imperforate hymen, transverse vaginal septum, vaginal agenesis, and Müllerian agenesis (Mayer-Rokitansky-Küster-Hauser syndrome).
5 - Amenorrhea from Enzymatic and Receptor Deficiencies
Congenital adrenal hyperplasia (17 alpha-hydroxylase deficiency), complete androgen insensitivity syndrome, gonadotropin resistance (rare), aromatase deficiencies (rare).