Basic Terms
- Puberty is a general term encompassing the entire transition from childhood to sexual maturity.
- Menarche (the onset of menstruation) occurs at an average age of 12 years (normal range 8–16 years).
- Menstrual cycles or “periods” are often irregular through adolescence before settling into a more consistent ovulatory pattern ranging from 24 days to 35 days (average 28 days). The average duration of menstruation is 3–7 days and blood loss is typically about 80 mL.
- Mittelschmerz refers to periovulatory, unilateral, pelvic pain that some women consistently experience.
- Menopause is defined as the cessation of menses and usually occurs around age 50. Women with continued bleeding beyond age 55 should be sampled to rule out malignancy.
Hormonal Regulation of Ovulation
The cyclopentenophenanthrene ring structure is the basic carbon skeleton for all steroid hormones. Cholesterol is the parent steroid from which all the glucocorticoids, mineralocorticoids, and gonadal steroids are derived.
Phases of the Menstrual Cycle
The menstrual phase begins on day 1 with the onset of bleeding and continues for several more days until the shedding of the endometrial lining stops (usually day 4–5).
- The proliferative phase begins at the end of the menstrual phase and ends at ovulation (usually day 13 or 14). This phase is characterized by endometrial thickening and ovarian follicular maturation.
- The luteal (secretory) phase starts at ovulation and lasts through day 28 before the entire process starts over again on day 1. Biologic basis of menstruation Coordination of the menstrual cycle depends on a complex interaction of the brain, pituitary, ovaries, and endometrium.
Brain
- The hypothalamus is located at the base of the brain and essentially functions as the central processing unit of the reproductive system.
- Neuronal stimuli from the cerebral cortex are converted by the hypothalamus into pulses of neuropeptides (gonadotropin-releasing hormone, GnRH).
- Hypothalamic GnRH production is modulated by negative feedback of steroid hormones (estradiol-17β, progesterone).
Pituitary
- Located just below the hypothalamus, the pituitary gland consists of the neurohypophysis (posterior lobe) and the adenohypophysis (anterior lobe). It is the anterior pituitary that gives rise to gonadotropin (luteinizing hormone [LH] and follicle-stimulating hormone [FSH]) production.
- Pulsatile GnRH from the hypothalamus initiates the synthesis and secretion of LH and FSH. Similar to the hypothalamus, the anterior pituitary is subject to negative feedback regulation by the steroid hormones.
- In women of reproductive age, LH and FSH levels generally remain in the 10–20 mIU/mL range. After the menopause or surgical oophorectomy, estradiol-17β levels decline and LH and FSH are released from negative feedback, achieving circulating concentrations of more than 50 mIU/mL.
Ovaries
- Primitive germ cells (oogonia) divide by mitosis during fetal embryogenesis, peaking at around 7 million by 5 months of gestation.
- Meiotic division then begins, resulting in the formation of primary oocytes. However, rapid atresia reduces the number of available follicles to 2 million at birth. At puberty, only around 300,000–400,000 follicles remain.
- Oocytes remain “resting” in meiotic prophase until puberty. Resting ovarian follicles are surrounded by thecal and granulosa cells: FSH stimulates the granulosa cells and LH stimulates the thecal cells.
- Only a single “dominant follicle” develops each menstrual cycle. When it produces enough estrogen to sustain circulating estradiol- 17β concentration of about 200 pg/mL for 48 hours, the hypothalamic-pituitary axis responds by secreting a surge of gonadotropins, primarily LH. This LH surge precedes ovulation by 24–36 hours.
- Following ovulation, the follicle collapses to form the corpus luteum. This endocrine organ mainly synthesizes progesterone to prepare the endometrium for pregnancy.
- If implantation does not occur, the corpus luteum will degenerate, resulting in a precipitous decline in circulating steroid hormone levels and the onset of menstruation. The decreasing steroid hormone levels release the negative feedback mechanism, inducing the pituitary to increase gonadotropin secretion. As a result, a new cycle of follicular recruitment is initiated.
If implantation does occur, the embryo will rescue the corpus luteum by producing human chorionic gonadotropin (hCG) to prevent menstruation. At 7–9 weeks of gestation, the placenta takes over the production of progesterone from the corpus luteum.
Endometrium
- Dramatic monthly cyclic changes occur in the endometrium under the control of steroid hormones produced by the ovaries.
- Estradiol-17β production by the ovarian follicles induces endometrial proliferation. Progesterone synthesis by the corpus luteum then acts to mature the estrogen-primed endometrium in preparation for blastocyst implantation.
- Lowered steroid hormone levels in the late secretory phase cause a collapse of the endometrial vasculature, resulting in menstruation.
Premenstrual syndrome (PMS)
• Definition –
Cyclic appearance of a constellation of myriad symptoms that affect lifestyle or work.
- Common manifestations include abdominal bloating, weight gain, constipation, anxiety, breast tenderness, depression, cravings for sugar or salt, and irritability.
- The diagnosis relies on a patient’s self-reporting symptoms that are predictably cyclic in nature and of sufficient severity to interfere with a day’s normal events.
- PMS is quite common and typically mild; 5–10% of women report severe symptomatology at some point in their lives and 1% have such severe PMS that it threatens their work and interpersonal relationships.
- Multiple etiologic factors have been proposed, but there is no unifying theory to explain the pathophysiology of PMS.
• Treatment –
Supportive therapy, aerobic exercise, and diet modification. Fluoxetine or sertraline has been shown to reduce symptoms of depression, anger, and anxiety.