Reproduction in females is controlled by hormones produced by the hypothalamus, anterior lobe of the pituitary gland, and ovaries.

Female Sex Hormones

The ovaries produce the two major groups of female sex hormones-estrogens and progesterone-plus inhibin, which aids estrogens in exerting an inhibitory effect on the anterior lobe of the pituitary gland via a negative-feedback mechanism. Ovarian follicles under the stimulation of FSH produce estrogens, a group of female sex hormones produced primarily by the ovaries. Estrogens stimulate the maturation of the female reproductive organs and the development and maintenance of the female secondary sex characteristics. The female secondary sex characteristics include development of the mammary glands and breasts, a broad pelvis, increased deposition of subcutaneous tissue (especially in the breasts, buttocks, and thighs), and increased blood supply to the skin. The development of axillary and pubic hair is stimulated by the small amount of androgens produced by the adrenal glands.

After ovulation, the portion of the ovarian follicle remaining in the ovary becomes the corpus luteum (kor’- pus lu’-te-um). Under stimulation by LH, the corpus luteum secretes the other female sex hormone, progesterone (pro-jes’-te-ron), as well as estrogens. The major role of progesterone is the development and maintenance of the endometrium in pregnancy, but it also inhibits uterine contractions and dilation of the cervix during pregnancy. Both estrogens and progesterone play major roles in the regulation of the female reproductive cycles.

Role of Hormones

Under control of the hypothalamic GnRH and anterior pituitary FSH and LH, the ovaries manufacture estrogens and progesterones.The hypothalamic-pituitary-ovarian axis mediates the events of the ovulatory cycle, including follicular development, ovulation, corpus luteum formation, and menstruation. In addition, the estrogens and progesterone stimulate sexual desire and exert additional effects throughout in the body.

Progesterone and the estrogens are synthesized from a 27-carbon cholesterol precursor. Progesterone has 21 carbons and is structurally most like cholesterol. The three estrogens have 18 carbons and are formed from the action of the enzyme aromatase on the “male” sex steroids testosterone and androstenedione.

Estrogens

Estrogens produce cyclic changes in the uterine endothelium and vaginal epithelium. Estrogens are steroids that are secreted in both males and females by the adrenal cortex and in females by the ovary (main source) and placenta. Natural estrogens include estradiol, estrone, and estriol. Estrogens in low doses may be used therapeutically as replacement hormone during menopause.

At puberty, estrogen stimulates breast growth (fatty tissue deposition, pigmentation), fat deposition in the vulva, bony pelvis growth and broadening, closure of the epiphyseal plates of long bones, vaginal epithelial changes, and general growth.

Progesterone

Progesterone is a steroid hormone that helps prepare the endometrium to receive and implant the fertilized ovum; it also promotes development of the placenta (a spongy structure in the uterus that provides nourishment for a developing fetus) and the mammary glands.

Progesterone is used therapeutically to treat threatened spontaneous abortion and such menstrual problems as dysmenorrhea or amenorrhea. It is secreted from the placenta and the corpus luteum under control of LH from the anterior pituitary. Progesterone plays a minor role in Na+ and water balance. It also influences nitrogen balance, breast function, and body temperature during the menstrual cycle, raising body temperature by 0.5°C in the postovulatory phase of the cycle.

Menarche

Menarche is the onset of menstruation. The average age for menarche in the United States is now 12.8 years. Menarche is preceded by puberty-induced body changes that occur between ages 9 and 16 years.

The age at which menarche occurs is affected by genetic and environmental factors. Menarche may be delayed by poor nutrition, high levels of exercise (athletes or dancers), and several medical conditions, such as diabetes mellitus, congenital heart disease, and ulcerative colitis. Early menarche may occur with other conditions, such as hypothyroidism, CNS tumors, and head trauma. Girls usually show an increase in height of only 2 to 3 inches after the onset of menstruation.

Early menstrual cycles are often irregular and anovulatory (not preceded by ovulation and discharge of an ovum). Although menstrual cycles may not be regular for several years, the woman is still potentially fertile.

Female Reproductive Cycles

The two female reproductive cycles are hormonally controlled and occur simultaneously starting at puberty: the ovarian cycle and the menstrual cycle. The ovarian cycle involves the monthly formation and release of a secondary oocyte and the ovarian events that take place in preparation for pregnancy. The menstrual cycle involves repetitive changes in the endometrium that lead to monthly menstruation if pregnancy does not occur. The lengths of these cycles range from 24 to 35 days in different women, but 28 days is about average.

Except for periods of pregnancy and nursing, women experience monthly reproductive cycles from puberty, at about 11 years of age, until menopause.

Ovarian Cycle

Puberty in females begins at about 11 years of age, with the first menstruation (menarche) occurring at about 13 years of age. The female reproductive cycles begin when the hypothalamus secretes GnRH, which activates the anterior lobe of the pituitary gland to release FSH and a small amount of LH.

Recall that the primary ooctyes are formed within the primordial ovarian follicles of the ovary prior to birth. The primordial ovarian follicles do not continue to mature at birth, instead they arrest development for several years. Beginning at puberty, during each ovarian cycle, FSH promotes the development of about 20 of the primordial ovarian follicles into primary ovarian follicles, each containing a primary oocyte whose follicular epithelial cells have grown from squamous to cuboidal cells. Some of these primary ovarian follicles then develop further into secondary ovarian follicles as their follicular epithelial cells multiply and become stratified. The appearance of small fluid-filled spaces within the secondary ovarian follicles marks the formation of tertiary ovarian follicles, each still containing a primary oocyte. The follicular epithelial cells surrounding the primary oocyte have now grown to become granulosa cells. The granulosa cells are responsible for secreting estrogens-as well as passing nutrients to the developing oocyte.

During each ovarian cycle, one dominant tertiary ovarian follicle will continue development. The remaining ovarian follicles undergo atresia, or death. The developing tertiary ovarian follicle continues to secrete low levels of estrogens, in addition to inhibin, into the blood. The low blood levels of estrogens, aided by inhibin, initiate a negative-feedback mechanism on GnRH and FSH, respectively. The inhibition of FSH secretion prevents development of additional ovarian follicles.

Even though the blood levels of FSH are low, increased sensitivity of the granulosa cells to FSH results in a rapid rise in the production of estrogens starting on day 7 of the ovarian cycle, and reaching a peak on day 12. At this high blood level, estrogens stimulate the stimulates ovulation, which releases the secondary oocyte surrounded by granulosa cells. Ovulation occurs 14 days before the onset of the next menstruation, regardless of the length of the cycle. In a 28-day ovarian cycle, days 1-14 are known as the follicular phase.

After ovulation, LH stimulates the transformation of the remaining granulosa cells into the corpus luteum. The corpus luteum secretes increasing amounts of progesterone and lesser amounts of estrogens during days 15 to 25. The increasing blood levels of progesterone, aided by estrogens released from the corpus luteum, begins a negative-feedback mechanism that inhibits the secretion of GnRH by the hypothalamus. The lack of GnRH, aided by the release of inhibin from the corpus luteum, inhibits the release of LH and FSH by the anterior lobe of the pituitary gland.

If the secondary oocyte is not fertilized, the corpus luteum degenerates into the nonfunctional corpus albicans when blood LH levels decline. Loss of the corpus luteum causes a rapid decline in the blood levels of estrogens and progesterone from days 25 to 28. Days 15-28 of the ovarian cycle are known as the luteal phase. Once the low blood level of progesterone no longer inhibits the hypothalamus and allow the secretion of GnRH, the next reproductive cycle begins. If the secondary oocyte is fertilized, the corpus luteum continues to enlarge and produce increasing amounts of progesterone and estrogens, and degenerates by 16 to 20 weeks of development.

Menstrual Cycle

The menstrual, or uterine, cycle refers to the series of changes in the endometrium that occur each month unless pregnancy occurs. These changes are responses to fluctuating blood levels of estrogens and progesterone. The menstrual cycle has four phases: menstruation, proliferative phase, secretory phase, and premenstrual phase.

Menstruation starts a new menstrual cycle. It begins on the first day of the next menstrual cycle and lasts from three to five days.

The proliferative phase is characterized by a buildup of the endometrium under stimulation by estrogens, whose concentration in the blood increases as the dominant tertiary ovarian follicle develops. This phase begins at the end of menstruation and ends at ovulation.

Following ovulation, both progesterone and estrogens are produced by the corpus luteum, and they continue the development of the endometrium in the secretory phase. Estrogens promote the continued thickening of the endometrium. Progesterone stimulates the formation of blood vessels and glands in the endometrium, preparing it to receive a preembryo. If fertilization of a secondary oocyte does not occur, the premenstrual phase begins. The blood levels of estrogens and progesterone drop rapidly, triggering the breakdown of the endometrium. This eventually leads to menstruation on the first day of the next menstrual cycle.

Menopause, the cessation of regular menstrual cycles, usually begins around age 45-55 and can last up to ten years. The onset is usually gradual with menstrual cycles becoming irregular. During this time, a woman can still conceive, so menopause is not considered to be complete until the cycles have not occurred for one year.

Aging of the ovaries is the cause of menopause. There are fewer primary ovarian follicles to respond to FSH and LH from the anterior lobe of the pituitary, and ovulation does not occur. Therefore, the secretion of estrogens and progesterone by the ovaries is greatly curtailed.

The decline in female sex hormones often is accompanied by physical symptoms such as headaches, insomnia, and depression. Hot flashes, caused by sudden and temporary dilation of dermal blood vessels, are perhaps the most common symptom. Hormone replacement therapy (HRT), the administration of estrogens and progesterone, was previously used to treat the unpleasant symptoms of menopause. Its use has been greatly curtailed because studies have shown that it increases the risk of breast cancer, strokes, and heart disease.