Review of Medical Physiology - William F. Ganong 2002

Endocrine System, Metabolism, and Reproduction
Sex Differentiation and Development
Female Reproductive System - Disorders of Ovarian Function

Menstrual cycle Disorders

Some infertile women experience anovulatory cycles, meaning they do not ovulate, yet menstruation occurs at relatively regular intervals. As noted above, anovulatory cycles are typical for the first year or two following menarche and preceding menopause. Amenorrhea refers to the absence of menstruation. If menstrual bleeding has never occurred, the condition is termed primary amenorrhea. Some women with primary amenorrhea exhibit underdeveloped breasts and other signs of sexual infantilism. The cessation of cycles in a woman with previously normal menstruation is known as secondary amenorrhea. Pregnancy is by far the most common cause of secondary amenorrhea, leading to the well-established clinical rule: secondary amenorrhea should be assumed to be due to pregnancy until proven otherwise. Other causes of amenorrhea include emotional stress and environmental changes, hypothalamic diseases, pituitary disorders, primary ovarian disorders, and various systemic illnesses. Evidence suggests that in some women with hypothalamic amenorrhea, the frequency of GnRH pulsatile release is slowed due to excessive hypothalamic opioid activity. Previous experiments have demonstrated that GnRH pulse frequency increases upon administration of the orally active opioid antagonist naltrexone.

The terms hypomenorrhea and menorrhagia are used to denote scanty or pathologically heavy bleeding, respectively, during regular cycles. Metrorrhagia refers to uterine bleeding between menstrual periods, whereas oligomenorrhea is characterized by infrequent menstruation. Dysmenorrhea means painful menstruation. Severe menstrual cramps are common in young women and typically disappear following a first pregnancy. Most symptoms of dysmenorrhea result from the accumulation of Prostaglandins in the Uterus, and consequently, they can be alleviated by the administration of prostaglandin synthesis inhibitors (see Chapter 17).

During the last seven to ten days of the menstrual cycle, some women experience symptoms such as irritability, abdominal bloating, edema, emotional lability, impaired concentration, depressive states, headaches, and constipation. These symptoms of premenstrual syndrome (PMS) are a consequence of salt and Water retention in the body. It remains unclear whether these or other hormonal changes occurring in the late luteal phase are responsible for this condition, as the duration and severity of symptoms do not change when the luteal phase is terminated prematurely by the administration of mifepristone, resulting in early menstruation. The antidepressant fluoxetine (Prozac), a serotonin reuptake inhibitor, and the benzodiazepine alprazolam help alleviate the symptoms, as do GnRH secretagogues administered at a dose that suppresses the pituitary-ovarian axis. It is not yet understood how these diverse clinical observations can be integrated into a coherent picture of PMS Pathogenesis.

Genetic Disorders

Numerous single-Gene Mutations occurring in women lead to reproductive disorders, such as Kallmann syndrome, which causes hypogonadotropic hypogonadism (see above); GnRH resistance, FSH resistance, and LH resistance resulting from defects in GnRH, FSH, and LH receptors, respectively; and aromatase deficiency, which prevents estrogen synthesis. All of these conditions are caused by loss-of-function mutations. An interesting gain-of-function mutation leads to McCune-Albright syndrome, in which G_sα acquires constitutive activity in some, but not all, Cells (The phenomenon of mosaicism). This syndrome results from somatic mutations occurring after the initial Cell Divisions of the embryo (see Chapter 1) and is associated with multiple endocrinopathies, including precocious Puberty and amenorrhea accompanied by galactorrhea.