The Reproductive System of the Female

A woman's reproductive system produces sex hormones and functional gametes and also must be able to protect and support a developing embryo and nourish the newborn infant. The principal organs of the female reproductive system are the ovaries , the uterine tubes , the uterus , the vagina , and the components of the external genitalia


As in males, a variety of accessory glands release their secretions into the female reproductive tract.
The ovaries, uterine tubes, and uterus are enclosed within an extensive mesentery known as the broad ligament . The uterine tubes run along the superior border of the broad ligament and open into the pelvic cavity lateral to the ovaries. The mesovarium, a thickened fold of mesentery, supports and stabilizes the position of each ovary.


Several other ligaments assist the broad ligament in supporting and stabilizing the position of the uterus and associated reproductive organs. These ligaments lie within the mesentery sheet of the broad ligament and are connected to the ovaries or uterus. The broad ligament limits side–to–side movement and rotation, and the other ligaments (described in our discussion of the ovaries and uterus) prevent superior– inferior movement.



The Ovariesare small, lumpy, almond–shaped organs near the lateral walls of the pelvic cavity. The ovaries perform three main functions: (1) produce immature female gametes, or oocytes, (2) secrete female sex hormones, including estrogens and progestins, and (3) secrete inhibin, involved in the feedback control of pituitary FSH production. 



A typical ovary is a flattened oval about 5 cm in length, 2.5 cm in width, and 8 mm in thickness and weighs 6–8 g (roughly 0.25 oz). An ovary is pink or yellowish and has a nodular consistency. The visceral peritoneum, or germinal epithelium , covering the surface of each ovary consists of a layer of columnar epithelial cells that overlies a dense connective–tissue layer called the tunica albuginea . We can divide the interior tissues, or stroma , of the ovary into a superficial cortex and a deeper medulla. Gametes are produced in the cortex.


Ovum production, or oogenesis begins before a woman's birth, accelerates at puberty, and ends at menopause


Between puberty and menopause, oogenesis occurs on a monthly basis as part of the ovarian cycle .
Unlike spermatogonia, the oogonia, or stem cells of females, complete their mitotic divisions before birth. Between the third and seventh months of fetal development, the daughter cells, or primary oocytes , prepare to undergo meiosis. They proceed as far as the prophase of meiosis I, but at that time the process comes to a halt. The primary oocytes then remain in a state of suspended development until the individual reaches puberty, when rising levels of FSH trigger the start of the ovarian cycle. Each month thereafter, some of the primary oocytes will be stimulated to undergo further development. Not all primary oocytes produced during development survive until puberty. The ovaries have roughly 2 million primordial follicles at birth, each containing a primary oocyte. By the time of puberty, the number has dropped to about 400,000. The rest of the primordial follicles degenerate in a process called atresia. Although the nuclear events under way in the ovaries during meiosis are the same as those in the testes, the process differs in two important details:

The cytoplasm of the primary oocyte is unevenly distributed during the two meiotic divisions. Oogenesis produces one functional ovum, which contains most of the original cytoplasm, and two or three polar bodies , nonfunctional cells that later disintegrate

The ovary releases a secondary oocyte rather than a mature ovum. The secondary oocyte is suspended in metaphase of meiosis II; meiosis will not be completed unless and until fertilization occurs.



In oogenesis, a single primary oocyte produces an ovum and two or three nonfunctional polar bodies.

The Ovarian Cycle
Ovarian follicles are specialized structures in which both oocyte growth and meiosis I occur. The ovarian follicles are located in the cortex of the ovaries. Primary oocytes are located in the outer portion of the ovarian cortex, near the tunica albuginea in clusters called egg nests .


After sexual maturation, a different group of primordial follicles is activated each month. This monthly process is known as the ovarian cycle .
The ovarian cycle can be divided into a follicular phase , or preovulatory phase , and a luteal phase , or postovulatory phase .




Follicle formation is stimulated by FSH from the anterior pituitary gland. The ovarian cycle begins as activated primordial follicles develop into primary follicles . In a primary follicle, the follicular cells enlarge and undergo repeated divisions that create several layers of follicular cells around the oocyte. These follicle cells are now called granulosa cells .


As layers of granulosa cells develop around the primary oocyte, microvilli from the surrounding granulosa cells intermingle with those of the primary oocyte. The microvilli are surrounded by a layer of glycoproteins; the entire region is called the zona pellucida . The microvilli increase the surface area available for the transfer of materials from the granulosa cells to the rapidly enlarging oocyte.

The conversion from primordial to primary follicles and subsequent follicular development occurs under FSH stimulation. As the granulosa cells enlarge and multiply, adjacent cells in the ovarian stroma form a layer of thecal cells around the follicle. Thecal cells and granulosa cells work together to produce sex hormones called estrogens .

The Formation of Secondary Follicles. Although many primordial follicles develop into primary follicles, only a few will proceed to the next step. The transformation begins as the wall of the follicle thickens and the granulosa cells begin secreting small amounts of fluid. This follicular fluid , or liquor folliculi , accumulates in small pockets that gradually expand and separate the inner and outer layers of the follicle. At this stage, the complex is known as a secondary follicle .


The Formation of a Tertiary Follicle. Eight to 10 days after the start of the ovarian cycle, the ovaries generally contain only a single secondary follicle destined for further development. By the 10th to the 14th day of the cycle, that follicle has formed a tertiary follicle , or mature Graafian  follicle , roughly 15 mm in diameter. This complex spans the entire width of the ovarian cortex and distorts the ovarian capsule, creating a prominent bulge in the surface of the ovary. The oocyte projects into the antrum , or expanded central chamber of the follicle.


Instead of producing two secondary oocytes, the first meiotic division yields a secondary oocyte and a small, nonfunctional polar body. The secondary oocyte then enters meiosis II, but stops once again on reaching metaphase. Meiosis II will not be completed unless fertilization occurs.
Generally, on day 14 of a 28–day cycle, the secondary oocyte and the surrounding granulosa cells lose their connections with the follicular wall. The granulosa cells immediately surrounding the secondary oocyte now drift free within the antrum and are known as the corona radiata.

Ovulation. At ovulation , the tertiary follicle releases the secondary oocyte. The distended follicular wall ruptures, discharging the follicular contents, including the secondary oocyte and corona radiata, into the pelvic cavity.


The Formation and Degeneration of the Corpus Luteum. The empty tertiary follicle initially collapses, and ruptured vessels bleed into the antrum. The remaining granulosa cells then invade the area, proliferating to create an endocrine structure known as the corpus luteum , named for its yellow color. This process occurs under LH stimulation.

The lipids contained in the corpus luteum are used to manufacture steroid hormones known as progestins principally the steroid progesterone. Although moderate amounts of estrogens are also secreted by the corpus luteum, levels are not as high as they were at ovulation, and progesterone is the principal hormone in the interval after ovulation. Its primary function is to prepare the uterus for pregnancy by stimulating the maturation of the uterine lining and the secretions of uterine glands.

Unless Fertilization Occurs, the Corpus Luteum Begins to Degenerate Roughly 12 Days After Ovulation. Progesterone and estrogen levels then fall markedly. Fibroblasts invade the nonfunctional corpus luteum, producing a knot of pale scar tissue called a corpus albicans. The disintegration, or involution , of the corpus luteum marks the end of the ovarian cycle. A new ovarian cycle then begins with the activation of another group of primordial follicles.


Age and Oogenesis

At puberty, each ovary contains about 200,000 primordial follicles. Forty years later, few if any follicles remain, although only about 500 will have been ovulated during the interim.


A woman in the United States has a 1 in 70 chance of developing ovarian cancer in her lifetime. In 2002, an estimated 23,300 ovarian cancers were diagnosed, and 13,900 women died from this condition. Although ovarian cancer is the third most common reproductive cancer among women, it is the most dangerous because it is seldom diagnosed in its early stages. The prognosis is relatively good for cancers that originate in the general ovarian tissues or from abnormal oocytes. These cancers respond well to some combination of chemotherapy, radiation, and surgery. However, 85 percent of ovarian cancers develop from epithelial cells, and sustained remission can be obtained in only about one–third of the cases of this type.


The Uterine Tubes ( Fallopian tube or oviduct ) is a hollow, muscular tube measuring roughly 13 cm (5 in.) in length. Each tube has 3 segments:

The Infundibulum. The end closest to the ovary forms an expanded funnel, or infundibulum , with numerous fingerlike projections that extend into the pelvic cavity. The projections are called fimbriae. The inner surfaces of the infundibulum are lined with cilia that beat toward the middle segment of the uterine tube, called the ampulla .

The Ampulla. The thickness of the smooth muscle layers in the wall of the middle segment, or ampulla , of the uterine tube gradually increases as the tube approaches the uterus.

The Isthmus. The ampulla leads to the isthmus, a short segment connected to the uterine wall.


Pelvic inflammatory disease (PID) in women is a major cause of sterility (infertility). An infection of the uterine tubes, PID affects an estimated 850,000 women each year in the United States. In many cases, sexually transmitted pathogens are involved. As much as 50–80 percent of all first cases may be due to infection by Neisseria gonorrhoeae , the organism responsible for symptoms of gonorrhea, a sexually transmitted disease. Invasion of the region by bacteria that normally reside in the vagina can also cause PID.


Recently, another sexually transmitted bacterium, belonging to the genus Chlamydia , has been identified as the probable cause of up to 50 percent of all cases of PID. Despite the fact that women with this infection may develop few, if any, symptoms, scarring of the uterine tubes can still produce infertility.


The Uterus provides mechanical protection, nutritional support, and waste removal for the developing embryo (weeks 1–8) and fetus (from week 9 to delivery). In addition, contractions in the muscular wall of the uterus are important in ejecting the fetus at the time of birth.


The uterus is a small, pear–shaped organ about 7.5 cm (3 in.) long with a maximum diameter of 5 cm (2 in.). It weighs 30–40 g (1–1.4 oz). In its normal position, the uterus bends anteriorly near its base, a condition known as anteflexion. In this position, the uterus tilts anteriorly, covering the superior and posterior surfaces of the urinary bladder.


Suspensory Ligaments of the Uterus
In addition to the broad ligament, three pairs of suspensory ligaments stabilize the position of the uterus and limit its range of movement.



Internal Anatomy of the Uterus
We can divide the uterus into two anatomical regions: the body and the cervix. The uterine body , or corpus , is the largest region of the uterus. The fundus is the rounded portion of the body superior to the attachment of the uterine tubes. The body ends at a constriction known as the uterine isthmus . The cervix  is the inferior portion of the uterus that extends from the isthmus to the vagina.

The tubular cervix projects about 1.25 cm (0.5 in.) into the vagina. Within the vagina, the distal end of the cervix forms a curving surface that surrounds the cervical os ( os , an opening or mouth), or external orifice of the uterus. The cervical os leads into the cervical canal , a constricted passageway that opens into the uterine cavity of the body at the internal os , or internal orifice .


The arteries to the uterus are extensively interconnected. This arrangement helps ensure a reliable flow of blood to the organ despite changes in its position and the changes in uterine shape that accompany pregnancy. Numerous veins and lymphatic vessels also supply each portion of the uterus.


The Uterine Wall  The wall has a thick, outer, muscular myometrium and a thin, inner, glandular endometrium, or mucosa . 


The endometrium contributes about 10 percent to the mass of the uterus. The glandular and vascular tissues of the endometrium support the physiological demands of the growing fetus. Vast numbers of uterine glands open onto the endometrial surface and extend deep into the lamina propria, almost to the myometrium. Under the influence of estrogen, the uterine glands, blood vessels, and epithelium change with the phases of the monthly uterine cycle .

The myometrium, the thickest portion of the uterine wall, forms almost 90 percent of the mass of the uterus. Smooth muscle in the myometrium is arranged into longitudinal, circular, and oblique layers. The smooth muscle tissue of the myometrium provides much of the force needed to move a large fetus out of the uterus and into the vagina.






Cervical cancer is the most common cancer of the reproductive system in women age 15–34. Roughly 12,800 new cases of invasive cervical cancer are diagnosed each year in the United States, and approximately 33 percent of the individuals will eventually die of the condition. Another 34,900 patients are diagnosed with a less aggressive form of cervical cancer.


The Uterine Cycle or menstrual cycle , is a repeating series of changes in the structure of the endometrium. The uterine cycle averages 28 days in length, but it can range from 21 to 35 days in healthy women of reproductive age. We can divide the cycle into three phases: (1) menses , (2) the proliferative phase , and (3) the secretory phase .


The uterine cycle begins with the onset of menses, an interval marked by the degeneration of the functional zone of the endometrium. This degeneration occurs in patches and is caused by the constriction of the spiral arteries, which reduces blood flow to areas of endometrium.


Deprived of oxygen and nutrients, the secretory glands and other tissues in the functional zone begin to deteriorate. Eventually, the weakened arterial walls rupture, and blood pours into the connective tissues of the functional zone. Blood cells and degenerating tissues then break away and enter the uterine lumen, to be lost by passage through the cervical os and into the vagina.


The sloughing off of tissue is gradual, and at each site repairs begin almost at once. Nevertheless, before menses has ended, the entire functional zone has been lost. The process of endometrial sloughing, called menstruation, generally lasts from one to seven days. Over this period roughly 35 to 50 ml of blood is lost. The process can be relatively painless. Painful menstruation, or dysmenorrhea , can result from uterine inflammation and contraction or from conditions involving adjacent pelvic structures.

The Proliferative Phase The basilar zone, including the basal parts of the uterine glands, survives menses intact. In the days after menses, the epithelial cells of these glands multiply and spread across the endometrial surface, restoring the integrity of the uterine epithelium. Further growth and vascularization result in the complete restoration of the functional zone. As this reorganization proceeds, the endometrium is in the proliferative phase . The restoration occurs at the same time as the enlargement of primary and secondary follicles in the ovary. The proliferative phase is stimulated and sustained by estrogens secreted by the developing ovarian follicles.


The Secretory Phase During the secretory phase of the uterine cycle, the endometrial glands enlarge, accelerating their rates of secretion, and the arteries that supply the uterine wall elongate and spiral through the tissues of the functional zone. This activity occurs under the combined stimulatory effects of progestins and estrogens from the corpus luteum. The secretary phase begins at the time of ovulation and persists as long as the corpus luteum remains intact.
Secretory activities peak about 12 days after ovulation. Over the next day or two, the glandular activity declines, and the uterine cycle comes to a close as the corpus luteum stops producing stimulatory hormones. A new cycle then begins with the onset of menses and the disintegration of the functional zone. The secretory phase generally lasts 14 days. As a result, you can determine the date of ovulation by counting backward 14 days from the first day of menses.


Menarche and Menopause The uterine cycle begins at puberty. The first cycle, known as menarche, typically occurs at age 11–12. The cycles continue until age 45–55, at menopause (MEN–o–pawz), the last uterine cycle. In the interim, the regular appearance of uterine cycles is interrupted only by circumstances such as illness, stress, starvation, or pregnancy.

If menarche does not appear by age 16, or if the normal uterine cycle of an adult woman becomes interrupted for six months or more, the condition of amenorrhea exists. Primary amenorrhea is the failure to initiate menses. This condition may indicate developmental abnormalities, such as nonfunctional ovaries, the absence of a uterus, or an endocrine or genetic disorder. It can also result from malnutrition: Puberty is delayed if leptin levels are too low. Transient secondary amenorrhea can be caused by severe physical or emotional stresses. In effect, the reproductive system gets "switched off." Factors that cause either type of amenorrhea include drastic weight loss, anorexia nervosa, and severe depression or grief. Amenorrhea has also been observed in marathon runners and other women engaged in training programs that require sustained high levels of exertion and severely reduce body lipid reserves.


In endometriosis, an area of endometrial tissue begins to grow outside the uterus. The cause is unknown; because this condition is most common in the inferior portion of the peritoneum, one possibility is that pieces of endometrium sloughed off during menstruation are in some way forced through the uterine tubes into the peritoneal cavity, where they reattach.  Treatment of endometriosis may involve hormonal therapy to suppress uterine cycles or surgical removal of the endometrial mass. If the condition is widespread, a hysterectomy (removal of the uterus) or oophorectomy (removal of the ovaries) may be required.


The Vagina
The vagina is an elastic, muscular tube extending between the cervix and the vestibule , a space bounded by the female external genitalia.

It serves as a passageway for the elimination of menstrual fluids.

It receives the penis during sexual intercourse and holds spermatozoa prior to their passage into the uterus.

It forms the inferior portion of the birth canal , through which the fetus passes during delivery.

The vagina and vestibule are separated by the hymen, an elastic epithelial fold that partially or completely blocks the entrance to the vagina before the initial sexual intercourse. The two bulbospongiosus muscles extend along either side of the vaginal entrance, which is constricted by their contractions. These muscles cover the vestibular bulbs , masses of erectile tissue on either side of the vaginal entrance. The vestibular bulbs have the same embryological origins as the corpus spongiosum of the penis in males.


The vagina contains a population of resident bacteria, usually harmless, supported by nutrients in the cervical mucus. The metabolic activity of these bacteria creates an acidic environment, which restricts the growth of many pathogens. Vaginitis, an inflammation of the vaginal canal, is caused by fungi, bacteria, or parasites. In addition to any discomfort that may result, the condition may affect the survival of spermatozoa and thereby reduce fertility. An acidic environment also inhibits the motility of sperm; for this reason, the buffers in semen are important to successful fertilization.


The External Genitalia is the vulva, or pudendum. The paraurethral glands , or Skene's glands , discharge into the urethra near the external urethral opening. Anterior to this opening, the clitoris projects into the vestibule. A small, rounded tissue projection, the clitoris is the female equivalent of the penis, derived from the same embryonic structures. Internally, it contains erectile tissue comparable to the corpora cavernosa of the penis. The clitoris engorges with blood during sexual arousal. A small erectile glans sits atop it; extensions of the labia minora encircle the body of the clitoris, forming its prepuce , or hood .


During sexual arousal, a pair of ducts discharges the secretions of the greater vestibular glands ( Bartholin's glands ) into the vestibule near the posterolateral margins of the vaginal entrance. These mucous glands have the same embryological origins as the bulbourethral glands of males.


The Mammary Glands are specialized organs of the integumentary system that are controlled mainly by hormones of the reproductive system and by the placenta , a temporary structure that provides the embryo or fetus with nutrients.


The glandular tissue of the mammary gland consists of separate lobes, each containing several secretory lobules. Ducts leaving the lobules converge, giving rise to a single lactiferous duct in each lobe. Near the nipple, that lactiferous duct enlarges, forming an expanded chamber called a lactiferous sinus .



The inactive, or resting , mammary gland is dominated by a duct system rather than by active glandular cells. The size of the mammary glands in a nonpregnant woman reflects primarily the amount of adipose tissue present, not the amount of glandular tissue. The secretory apparatus does not complete its development unless pregnancy occurs. The active mammary gland is a tubuloalveolar gland, consisting of multiple glandular tubes that end in secretory alveoli.


Breast cancer is a malignant, metastasizing cancer of the mammary gland. It is the leading cause of death in women between the ages of 35 and 45, but it is most common in women over age 50. Approximately 39,600 deaths will occur in the United States from breast cancer in 2002, and approximately 203,500 new cases will be reported. An estimated 12 percent of women in the United States will develop breast cancer at some point in their lifetime, and the rate is steadily rising. The incidence is highest among Caucasian–Americans, somewhat lower in African–Americans, and lowest in Asian–Americans and American Indians. Notable risk factors include (1) a family history of breast cancer, (2) a first pregnancy after age 30, and (3) early menarche (first menstrual period) or late menopause (last menstrual period). Breast cancers in males are very rare, but about 400 men die from the disease each year in the United States.

Despite repeated studies, no links have been proven between breast cancer and oral contraceptive use, estrogen therapy, fat consumption, or alcohol use. It appears likely that multiple factors are involved.


Hormones and the Female Reproductive Cycle


hormonal control that involves an interplay between secretions of both the pituitary gland and the gonads. But the regulatory pattern in females is much more complicated than in males, because it must coordinate the ovarian and uterine cycles. Circulating hormones control the female reproductive cycle , coordinating the ovarian and uterine cycles to ensure proper reproductive function. If the two cycles cannot be coordinated in a normal manner, infertility results. A woman who fails to ovulate cannot conceive, even if her uterus is perfectly normal. A woman who ovulates normally, but whose uterus is not ready to support an embryo, will be just as infertile.


Hormones and the Follicular Phase
Follicular development begins under FSH stimulation; each month some of the primordial follicles begin to develop into primary follicles. As the follicles enlarge, thecal cells start producing androstenedione , a steroid hormone that is a key intermediate in the synthesis of most sex hormones Androstenedione is absorbed by the granulosa cells and converted to estrogens. In addition, small quantities of estrogens are secreted by interstitial cells scattered throughout the ovarian stroma. Circulating estrogens are bound primarily to albumins, with lesser amounts carried by gonadal steroid–binding globulin (GBG).


Three estrogens circulate in the bloodstream: (1) estradiol, (2) estrone, and (3) estriol. All have similar effects on their target tissues. Estradiol is the most abundant estrogen, and its effects on target tissues are most pronounced. It is the dominant hormone prior to ovulation. In estradiol synthesis, androstenedione is first converted to testosterone, which the enzyme aromatase converts to estradiol. The synthesis of both estrone and estriol proceeds directly from androstenedione.

Estrogens have multiple functions that affect the activities of many tissues and organs throughout the body. Among the important general functions of estrogens are (1) stimulating bone and muscle growth, (2) maintaining female secondary sex characteristics, such as body hair distribution and the location of adipose tissue deposits, (3) affecting central nervous system (CNS) activity (especially in the hypothalamus, where estrogens increase the sexual drive), (4) maintaining functional accessory reproductive glands and organs, and (5) initiating the repair and growth of the endometrium.






Hormones and the Luteal Phase
The high LH levels that trigger ovulation also promote progesterone secretion and the formation of the corpus luteum.  Although moderate amounts of estrogens are secreted by the corpus luteum, progesterone is the main hormone of the luteal phase. Its primary function is to continue the preparation of the uterus for pregnancy by enhancing the blood supply to the functional zone and stimulating the secretion of the endometrial glands.


Progesterone levels remain high for the next week, but unless pregnancy occurs, the corpus luteum begins to degenerate. Roughly 12 days after ovulation, the corpus luteum becomes nonfunctional, and progesterone and estrogen levels fall markedly. The blood supply to the functional zone is restricted, and the endometrial tissues begin to deteriorate. As progesterone and estrogen levels drop, the GnRH pulse frequency increases, stimulating FSH secretion by the anterior lobe of the pituitary gland, and the ovarian cycle begins again.
The hormonal changes involved with the ovarian cycle in turn affect the activities of other reproductive tissues and organs. At the uterus, the hormonal changes maintain the uterine cycle.


Hormones and the Uterine Cycle The declines in progesterone and estrogen levels that accompany the degeneration of the corpus luteum result in menses. The sloughing off of endometrial tissue continues for several days, until rising estrogen levels stimulate the repair and regeneration of the functional zone of the endometrium. The proliferative phase continues until rising progesterone levels mark the arrival of the secretory phase. The combination of estrogen and progesterone then causes the enlargement of the endometrial glands and an increase in their secretory activities.


Hormones and Body Temperature
The monthly hormonal fluctuations cause physiological changes that affect the core body temperature. During the follicular phase, when estrogen is the dominant hormone, the basal body temperature , or the resting body temperature measured on awakening in the morning, is about 0.3 deg C lower than it is during the luteal phase, when progesterone dominates. At the time of ovulation, the basal body temperature declines noticeably, making the rise in temperature over the next day even more noticeable. As a result, by keeping records of body temperature over a few uterine cycles, a woman can often determine the precise day of ovulation. This information can be important for individuals who wish to avoid or promote a pregnancy, because fertilization typically occurs within a day of ovulation. Thereafter, oocyte viability and the likelihood of successful fertilization decrease markedly.


Birth Control Strategies

Sterilization is a surgical procedure that makes an individual unable to provide functional gametes for fertilization. Either sexual partner may be sterilized. In a vasectomy, a segment of the ductus deferens is removed, making it impossible for spermatozoa to pass from the epididymis to the distal portions of the reproductive tract. After a vasectomy, the man experiences normal sexual function, because the secretions of the epididymis and testes normally account for only about 5 percent of the volume of semen. Spermatozoa continue to develop, but they remain within the epididymis until they degenerate. The failure rate for this procedure is 0.08 percent.


The uterine tubes can be blocked by a surgical procedure known as a tubal ligation. The failure rate for this procedure is estimated at 0.45 percent. Because the surgery requires that the abdominopelvic cavity be opened, complications are more likely than with vasectomy.


Oral contraceptives manipulate the female hormonal cycle so that ovulation does not occur. The contraceptive pills produced in the 1950s contained relatively large amounts of estrogen and progestins. These concentrations were adequate to suppress pituitary production of GnRH, so FSH was not released and ovulation did not occur. In most of the oral contraceptive products developed subsequently, smaller amounts of estrogens have been used. Current combination pills differ significantly from the earlier products in that the hormonal doses are much lower, with only one–tenth the progestins and less than half the estrogens.


The failure rate for the combination oral contraceptives, when used as prescribed, is 0.24 percent over a two–year period. Birth control pills are not risk free: Combination pills can worsen problems associated with severe hypertension, diabetes mellitus, epilepsy, gallbladder disease, heart trouble, and acne. Women taking oral contraceptives are also at increased risk of venous thrombosis, strokes, pulmonary embolism, and (for women over 35) heart disease.


Three progesterone–only forms of birth control are now available: the system, and the progesterone–only pill. Depo–provera is injected every 3 months. Uterine cycles are initially irregular, and in roughly 50 percent of women using this product they eventually cease. The major problems with this contraceptive method are (1) a tendency to gain weight after three or more years of using it and (2) a slow return to fertility (up to 18 months) after injections are discontinued. The (silicone rubber) tubes of the Norplant system are saturated with progesterone and inserted under the skin. This method provides birth control for approximately five years, but to date the relatively high cost has limited its use. Because it does not supply estrogen, it produces fewer hormonal side effects than combination pills do. Fertility returns immediately after the removal of a Norplant device. Both Depo–provera and the Norplant system are easy to use and are extremely convenient. The progesterone–only pill is taken daily and may cause irregular uterine cycles. Skipping just one pill may result in pregnancy.


Although pregnancy is a natural phenomenon, it has risks, and the mortality rate for pregnant women in the United States averages about 8 deaths per 100,000 pregnancies. That average incorporates a broad range: The rate is 5.4 per 100,000 women under 20, but 27 per 100,000 among women over 40. Although these risks are small, for pregnant women over age 35 the chances of dying from complications related to pregnancy are almost twice as great as the chances of being killed in an automobile accident and are many times greater than the risks associated with the use of oral contraceptives. For women in developing nations, the comparison is even more striking: The mortality rate for pregnant women in parts of Africa is approximately 1 per 150 pregnancies. In addition to preventing pregnancy, combination birth control pills have been shown to reduce the risks of ovarian and endometrial cancers and fibrocystic breast disease.


Menopause typically occurs at age 45–55, but in the years preceding it, the ovarian and uterine cycles become irregular.  Menopause is accompanied by a decline in circulating concentrations of estrogen and progesterone and a sharp and sustained rise in the production of GnRH, FSH, and LH. The decline in estrogen levels leads to reductions in the size of the uterus and breasts, accompanied by a thinning of the urethral and vaginal epithelia. The majority of women experience only mild symptoms, but some individuals experience acutely unpleasant symptoms in perimenopause or during or after menopause. For most of those individuals, hormone replacement therapies involving a combination of estrogens and progestins can prevent osteoporosis and the neural and vascular changes associated with menopause. The hormones are administered as pills, by injection, or by transdermal "estrogen patches." The synthetic hormone etidronate inhibits osteoporosis by suppressing osteoclast activity.


The Male Climacteric Changes in the male reproductive system occur more gradually than do those in the female reproductive system. The period of change is known as the male climacteric . Levels of circulating testosterone begin to decline between the ages of 50 and 60, and levels of circulating FSH and LH increase. Although sperm production continues (men well into their eighties can father children), older men experience a gradual reduction in sexual activity. This decrease may be linked to declining testosterone levels. Some clinicians suggest the use of testosterone replacement therapy to enhance the libido (sexual drive) of elderly men.