Contraception and the menstrual cycle

The menstrual cycle

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The menstrual cycle

One can analyze the menstrual cycle from many different points of view. The lay person is primarily aware of episodic uterine bleeding, the more or less regular interval between the bleeding episodes, and the interruption of the cycles by pregnancy.

The menstrual cycle is a series of natural changes in hormone production and the structures of the uterus and ovaries of the female reproductive system that make pregnancy possible. The ovarian cycle controls the production and release of eggs and the cyclic release of estrogen and progesterone. The uterine cycle governs the preparation and maintenance of the lining of the uterus (womb) to receive a fertilized egg.

Naturally occurring hormones drive the cycles; the cyclical rise and fall of the follicle stimulating hormone prompts the production and growth of oocytes (immature egg cells). The hormone estrogen stimulates the uterus lining to thicken to accommodate an embryo should fertilization occur. The blood supply of the thickened lining (endometrium) provides nutrients to a successfully implanted embryo. If implantation does not occur, the lining breaks down and blood is released. Triggered by falling progesterone levels, menstruation (a “period”, in common parlance) is the cyclical shedding of the lining, and is a sign that pregnancy has not occurred

The hypothalamus and the pituitary, however, orchestrate a month-long interaction of the hypothalamic-releasing factors, pituitary gonadotropins, and steroid hormones. In the ovary, the morphologic and endocrine events of dominant follicle maturation and ovulation contrast sharply with the more sedate background of relentless early follicle development and subsequent atresia (only one follicle ovulates out of every 999 which initiate development).

Contraception and the menstrual cycle

Meanwhile, the endometrium sees and responds to the cyclic and sequential appearances of estradiol and progesterone. The biochemist measures the concentrations of the relevant hormones in plasma throughout the cycle and wonders how these circulating hormones reflect or cause the key events in the menstrual cycle. Thus, the view that a person, or an organ, has of the menstrual cycle is highly relative to the position from which it is observed

Interaction of Hypothalamus, Pituitary, and Ovary

It is logical to begin an analysis of the hormonal interactions with the observation that as the corpus-luteum involutes after a cycle in which conception has not occurred, pituitary FSH release is increased in response to declining estrogen and progesterone concentration. The resulting rise in circulating FSH stimulates follicle growth and induces activity of the aromatase enzyme system necessary for estradiol synthesis.

This process of recruiting a cohort of follicles from among which one will typically become dominant takes place by about the fifth day of the average menstrual cycle. More intense gonadotropin stimulation before this time in the cycle usually leads to multiple follicle maturations such as the use of gonadotropins for the treatment of infertility and in-vitro fertilization.

In response to FSH stimulation, the responsive follicles secrete estradiol, which feeds back to suppression FSH release from the pituitary, the estradiol concentration continues to rise, ultimately in exponential fashion, throughout the follicular phase of the menstrual cycle despite the declining levels of FSH. The explanation of this phenomenon lies within the micro environment of the ovarian follicle. By the last few days before ovulation, virtually all of the ovarian estradiol secreted is produced by the ovary, and primarily by the follicle destined to ovulate.

The surge of estradiol secretion at this time is responsible for the mid- cycle surge of LH, a positive feedback of estradiol. In women, the amount of estradiol necessary to produce a positive feedback effect on LH release is a concentration of 200 pg/ml or more sustained for about 50 hours. Long-term high concentrations of estrogens lead to pituitary suppression (as with oral contraceptive pills). Ovulation occurs about 29 to 39 hours after the LH surge begins.

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After ovulation, the corpus luteum secretes progesterone at the rate of about 25 mg/day, yielding serum concentrations of the hormone typically between 5 and 25 ng/ml. This rate of steroid production by the early corpus luteum is roughly equal to the entire steroid output of both adrenal glands. In addition, the corpus luteum also secretes estradiol and 17-hydroxyprogesterone, an intermediate metabolite between progesterone and estrogen

After rupture and release of the ovum, capillaries penetrate the granulosa layer, enabling the delivery of circulating cholesterol, the necessary substrate for progesterone biosynthesis. In the face of these levels of sex steroid secretion, FSH concentration declines even further, whereas LH secretion levels plateau and is important in stimulation of the corpus luteurn.

If conception does not occur, the potent LH-surrogate, hCG, does not arrive on the scene to sustain corpus luteum function. Through sustained intra-ovarian processes of programmed cell death, the corpus luteum involutes 12 to 14 days after ovulation. Serum sex steroid concentrations fall, and menstruation ensues.

Endometrial Response during the Menstrual Cycle  

Estradiol is clearly a mitogen in the endometrium. At histologic analysis of endometrial tissue, glandular mitoses are typically seen. An increased risk of andenocarcinoma of the endometrium is associated with exposure over a period of many years to significant amounts of estrogen, either ingested orally, administered parenterally, or formed endogenously, typically by extraglandular aromatization of circulating androgens. This stimulation, without the naturally occurring progesterone from ovulation, or the administration of progestin, may lead to a hyperplastic endometrium and potentially, to cancer.

Mitoses are almost never seen in endometrial specimens during the postovulatory phase of the menstrual cycle, and the incidence of adenocareinoma of the endometrium in premenopausal women with normal ovulatory function is nearly zero. This also explains the protective effect of oral contraceptives against endometrial cancer, as these medications always include a progestin. 

Falling progesterone in the secretary endometrium leads to the local production of prostaglandin by the decidua (the part of the endometrium which is sloughed each month).  Prostaglandin causes vasospasm of the spiral arterioles, and subsequent ischemia and sloughing of the endometrium is what patients experience as a “periods.’ The uterine cramping associated with the normal ovulatory cycle is caused by this prostaglandin’s action and explains the effectiveness of prostaglandin inhibitors (aspirin or ibuprofen) in the treatment of dysmenorrhea.

Menstruation

Menstruation (also known as a period and many other colloquial terms) is the regular discharge of blood and mucosal tissue from the inner lining of the uterus through the vagina. Menstruation is the cyclical shedding of the lining and is triggered by falling progesterone levels. It is a sign that pregnancy has not occurred. The menstrual cycle occurs due to the rise and fall of hormones.

In humans, the first period, a point in time known as menarche, usually begins between the ages of 12 and 15, although menstruation may occasionally start as young as 8 years and still be considered normal. The average age of the first period is generally later in the developing world, and earlier in the developed world. The typical length of time between the first day of one period and the first day of the next is 21 to 45 days in young women, and 21 to 31 days in adults (an average of 28 days). Bleeding usually lasts around 2 to 7 days. Periods stop during pregnancy and typically do not resume during the initial months of breastfeeding. Menstruation stops occurring after menopause, which usually occurs between 45 and 55 years of age.

Up to 80% of women do not experience problems sufficient to disrupt daily functioning as a result of menstruation, although they may report having some issues prior to menstruation. Symptoms interfere with normal life, qualifying as premenstrual syndrome, in 20 to 30% of women. In 3 to 8%, symptoms are severe. These include acne, tender breasts, bloating, feeling tired, irritability, and mood changes. A lack of periods, known as amenorrhea, is when periods do not occur by age 15 or have not occurred in 90 days. Other experiences during the menstrual cycle include painful periods and abnormal bleeding such as bleeding between periods or heavy bleeding

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