Pathophysiology

The Menstrual Cycle

The cycle of menstruation begins with menarche, usually around age 12, and continues to occur in non-pregnant women until menopause, usually around age 50 [Rebar, 2000]. The cycle includes the vaginal discharge of sloughed endometrium called menses or menstrual flow. Three phases comprise the menstrual cycle: the follicular (or preovulatory), the ovulatory, and the luteal (or postovulatory).

The Menstrual Cycle Phase Duration
The median menstrual cycle length is 28 days, but can range from 21 to 40 days [Rebar, 2000]. Generally, variation is greatest and follicular and luteal phases are longest in the years immediately after menarche and before menopause, when anovulatory cycles are more common [Rebar, 2000; Beers, 1999].

Phase Phase Duration

Follicular Begins with first day of menses and ends on day prior to luteinizing hormone (LH) surge; menses usually lasts 5±2 days (the length of the follicular phase is the most variable of the three phases) [Beers, 1999]

Ovulatory Begins with day prior to LH surge and ends on day following surge

Luteal Usually lasts 14 days (the length of the luteal phase is the most constant of the three phases) [Rebar, 2000; Beers, 1999]

The Pituitary Hormone Cycle

Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) promote maturation of ova and stimulate secretion of estrogen and progesterone from ovaries

Phase Phase Characteristics

Follicular LH is released slowly from anterior pituitary gland; FSH is released slowly (release began in last luteal phase); level of FSH falls slightly after early increase of this hormone in this phase

Ovulatory LH released rapidly (LH surge); FSH levels peak

Luteal If ovum not fertilized, LH and FSH levels decrease

The Ovarian Cycle
Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) promote maturation of ova and stimulate secretion of estrogen and progesterone from ovaries

Phase Phase Characteristics

Follicular Single follicle is selected for maturation; estrogen, and progesterone constantly secreted from ovaries, although amount is small early in phase; accelerated release of estrogen late in phase to peak at day prior to or day of LH surge; significant increase in progesterone levels just before LH surge

Ovulatory Eruption of ovum from mature follicle after onset of LH surge

Luteal If the ovum is not fertilized, estrogen levels decrease and progestrone levels increase to peak then decrease

The Endometrial Cycle
The endometrium, the lining of the uterus, is composed of glandular cells that respond to estrogen and progesterone. The superficial and intermediate layers of the endometrium are sloughed during menses; the basal layer remains to regenerate the superficial and intermediate layers.

Phase Phase Characteristics

Follicular Menses begins (average blood loss of 130 mL—range, 13 to 300 mL) [Beers, 1999]; flow usually greatest on second day; after menses, endometrial glands proliferate in response to estrogen; mucosal lining thickens and becomes highly vascular

Ovulatory Maintenance of the endometrium

Luteal If the ovum not fertilized, necrosis of endometrium and constriction of blood vessels, which stops blood supply to superficial layer; cell death occurs and menses begins; local release of prostaglandins

Pathogenesis

Prostaglandins released from the endometrium in the late luteal and early follicular phases of the menstrual cycle cause uterine muscles to contract, sloughing the superficial and intermediate layers of the endometrium. Excessive production of prostaglandins is thought to cause abnormal uterine activity and result in uterine hypoxia and ischemia [Dawood, 1985; Pulkkinen, 1983]. In fact, women with primary dysmenorrhea have been shown to have higher levels of prostaglandins in the endometrium and menstrual fluid than women without the disorder [Coco, 1999; Pulkkinen, 1983].

While is it is generally thought that prostaglandins have a significant role in primary dysmenorrhea, some studies have also implicated leukotrienes and vasopressin as a source of pain [Abu, 2000], but the theory is not well-established [Coco, 1999].

The mechanisms of secondary dysmenorrhea are not well understood. However, it is thought that they also involve excessive production of prostaglandins or uterine contractions secondary to an obstruction, mass, or foreign body [Rapkin, 1996].

References

Abu JI, Konje JC. Leukotrienes in gynaecology: the hypothetical value of anti-leukotriene therapy in dysmenorrhoea and endometriosis. Hum Reprod Update. 2000;6(2):200-205.

Coco AS. Primary dysmenorrhea. Am Fam Physician. 1999;60(2):489-496.

Dawood MY. Dysmenorrhea. J Reprod Med. 1985;30(3): 154-167.

Pulkkinen MO. Prostaglandins and the non-pregnant uterus: the pathophysiology of primary dysmenorrhea. Acta Obstet Gynecol Scand Suppl. 1983;133:63-67.

Rapkin AJ. Pelvic pain and dysmenorrhea. In Berek JS, Adashi EY, Hillard, PA. Novak’s Gynecology, 12th ed. Baltimore, Md: Williams & Wilkins, 1996.

Rebar RW, Erickson GF. Menstrual cycle and fertility. In Goldman L, Bennett JC, eds. Cecil Textbook of Medicine, 21st ed. Philadelphia: WB Saunders; 2000.

Reproductive endocrinology. In Beers MH, Berkow R, eds. The Merck Manual of Diagnosis and Therapy, 17th ed. Whitehouse Station, NJ: Merck Research Laboratories; 1999.

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