1. Introduction
The reproductive anatomy and physiology of the human female is more complex than the male because it serves more purposes. Whereas the male needs only to produce and deliver gametes, the female must do this as well as provide nutrition and safe harbor for fetal development and then give birth and nourish the infant. Furthermore, female reproductive physiology is cyclic and female hormones are secreted in a more complex sequence compared to the relatively steady, simultaneous secretion of regulatory hormones in the male.
2. The Female Reproductive System
2.1 Roles
- To produce the female sex cells (egg cells) in the ovaries
- To deliver the egg into the oviduct where fertilization may occur
- To get the wall of the uterus into a condition favourable for implantation and development of an embryo
- To produce the chief female sex hormones progesterone and estrogen
3. Anatomy of the Female Reproductive System
3.1 Primary Sexual Organs: Ovaries
3.1.1 Structure
It is small, elongated and somewhat flattened. Its size is 5 cm long and 1 – 1.5 cm thick and it is held in position near the base of the abdominal cavity by ligaments. The ligaments contain major blood vessels of the ovary, ovarian artery and ovarian vein. These vessels are connected to the ovary at the ovarian hilum.
3.1.2 Functions
Firstly, it is to produce female gametes. No oogonia is formed after fetal life. 400,000 follicles are formed at birth and about 70,000 between 25 – 40 years of age.
Secondly, being an endocrine gland, it secretes female hormones including estrogens and progestins as well as inhibin, involved in the feedback control of pituitary follicle-stimulating hormone (FSH) production.
3.1.3 A Section through an Ovary
A cross section of an ovary reveals a cortex and a vascular medulla. In microscopic view, it can be seen that each ovary may consists of the following parts.
3.1.3.1 Germinal Epithelium
A layer of simple cubiodal epithelium that covers the free surface of the ovary.
3.1.3.2 Tunica Albuginea
A capsule of collagenous connective tissue immediately below the germinal epithelium.
3.1.3.3 Stroma
It is a region of connective tissue below the tunica albuginea. It is composed of an outer, denser layer called the cortex and an inner, looser layer called the medulla. The cortex contains the ovarian follicles.
3.1.3.4 Follicles
The cortex contains round epithelial vesicles called follicles, the actual centres of ovum production. Follicles consist of an oocyte surrounded by a single layer of flattened epithelium-like cells. If these cells are one layer thick, they are called follicle cells. If they are more than one cell thick, they are called granulose cells. They progress through various stages of development and mature into ova.
Follicles are always present in several stages of development and are slassified according to these different stages.
Primodial follicles are in the earliest stage of follicle development. They appear to have one layer of squamous-like follicular cells around the oocyte. They are the only ones present prior to puberty and constitute the majority thereafter.
A primary follicle consists of 2 or more layers of cubiodal or columnar cells around the primary oocyte.
A primary follicle becomes a secondary follicle when a fluid-filled space known as the antrum develops, while still containing the primary oocyte. The secondary follicle is surrounded by the theca, which consists of theca interna (an inner, highly vascularized layer of secretory cells) and the theca externa (an outer layer of connective tissue cells).
A vesicular (Graafian) follicle is the mature follicle with the secondary oocyte located on the stalk of granulose cells. Vesicular follicles bulge onto the surface of the ovary, and one follicle each month releases its oocyte from the ovary in a process called ovulation. It mainly secretes estrogens.
The follicular structure left behind in the ovary after ovulation (i.e. after extrusion of an ovum) is known as the corpus luteum (yellow body). It functions as a temporary endocrine tissue that secretes estrogens and progesterone which stop additional ovulation and stimulate the thickening of the uterine wall and the development of the mammary glands in anticipation of pregnancy. If pregnancy does not occur within 14 days after the formation of the corpus luteum, it degenerates into the corpus albicans, a form of white scar tissue.
3.2 Secondary Sexual Organs
3.2.1 Oviducts
They are also known as fallopian tubes or uterine tubes. They occur in a pair. They are muscular in nature and convey female eggs from the ovary to the uterus. The tubes are not directly connected to the ovaries. Their lumen is ciliated by ciliated epithelium. The female gamete moves by peristaltic movement of the tube.
There are 3 distinct portions of the oviducts.
3.2.1.1 Infundibulum
It is the end nearest to the ovary. It is fringed by feathery fimbriae. It appears as an expanded funnel which may actually overlap the ovary. Each month, as a secondary oocyte is released, it is effectively swept across a tiny gap between the tube and the ovary into the infundibulum by the motion of cilia in the fimbriae. Few oocytes are ever lost in the abdominal cavity. Unlike sperm, the secondary oocyte is unable to move on its own. Instead, it is carried along the uterine tube towards the uterus by the peristaltic contractions of the tube and the wavering movements of the cilia in the mucous membrane.
3.2.1.2 Ampulla
It is a thin-walled structure in the middle of the oviducts. The thickness of the smooth muscle layers in the wall gradually increases as it approaches the uterus. Fertilization of the secondary oocyte usually occurs in the ampulla (middle) of the tube. Penetration of the secondary oocyte by the sperm initiates the development of the mature ovum. An unfertilized egg will degenerate in the uterine tube. A fertilized oocyte (zygote) continues its journey towards the uterus, where it will become implanted. The zygote’s journey takes 4 to 7 days.
3.2.1.3 Isthmus
It is a short segment. It is the opening of the oviduct into the uterus.
3.2.2 Uterus
It is also known as the womb. It is a hollow, muscular organ in front of the rectum and behind the urinary bladder. It is a thick-walled organ. The uterus is a minute fluid-filled cavity. It is shaped like an inverted pear when viewed anteriorly. It however increases 3 to 6 times its size during the 9 calendar months of pregnancy. The fundus is the wide upper portion. The uterine tubes enter the uterus below the fundus. The body is the tapering middle portion which terminates in the narrow cervix, the juncture between the uterus and the vagina. The isthmus is the constricted region between the body and the cervix. The cervical canal is the interior of the cervix and opens into the vagina. The uterine cavity is the interior of the uterus and appears as just a slit in a non-pregnant woman.
3.2.2.1 Histology of the Uterus
It consists of 3 layers.
3.2.2.1.1 Perimetrium
It is also known as the serosal layer and has a serous coat and is the outer lining. It has squamous epithelium and underlying loose connective tissue.
3.2.2.1.2 Myometrium
It is a thick wall made of smooth muscles and forms the bulk of the uterus wall. It is sensitive to oxytocin during birth. These muscles are capable of stretching during pregnancy to accommodate one or more growing fetuses. They also contract during a woman’s orgasm. The myometrium is almost a centimeter thick but becomes even thicker during pregnancy in preparation for child birth.
3.2.2.1.3 Endometrium
It is a smooth, soft epithelium which contains an abundant supply of blood vessels and is pitted with simple tubular glands and is the inner lining of the uterus. It is composed of 2 layers, the inner stratum functionalis (aka the functional zone) and the outer functionalis (aka the basilar zone). Every month, in response to estrogen secretion, the endometrium thickens in preparation for the possible implantation of a fertilized ovum (the beginning of pregnancy). Secretions of progesterone help the endometrium develop active glands that make the endometrium rich in nutrients and ready to receive a fertilized ovum.
If implantation does not occur, the stratum functionalis is shed together with blood and glandular secretions, through the cervical canal and vagina. This breakdown of the endometrium makes up the menstrual flow in the process of menstruation. The stratum basalis layer is permanent and from it, a new stratum functionalis regenerates after the 3- to 5-day menstrual period. If fertilization and implantation does occur, the uterus houses, nourishes and protects the developing fetus within its muscular walls. As the pregnancy continues, estrogen secretions develop the smooth muscle in the uterine walls in preparation for the expulsive action of child birth.
3.2.3 Cervix
It is made mostly of dense connective tissue about 2.5 cm in length. The opening of the cervix into the vagina is almost at a right angle to the long axis of the vagina. It is covered interiorly by a mucous secreting ciliated epithelium at the upper regions and by stratified squamous epithelium at the vaginal end. It is cylindrical in shape and is continuous with the body of the uterus. The cervical canal is spindle-shaped and being constricted and is lined by tall columnar epithelium.
Ovulation may be confirmed by examination of the cervical mucus in mid-cycle as this will reveal characteristic changes if ovulation has occurred. Ovulatory mucus is clear and copius and can be drawn out into a fine thread (called spinnbarkheit). On drying, it crystallizes out into a characteristic fern-like pattern. Sperm penetration of the cervical mucus occurs more readily at the time of ovulation and this is clearly observed in the postcoital test. This test must be carried out at the time of ovulation and some 6 – 12 hours after intercourse has taken place. The number of progressively motile sperm in a number of high powered fields is examined. Normally, a large number of active sperm will be seen.
3.2.4 Vagina
It is an elastic, muscular tube lined with mucous membrane and is about 8 to 10 com long. It functions as a passage way for the menstrual flow, a receptacle for the penis during sexual intercourse and serves as the lower portion of the birth canal through which the fetus passes during delivery.
Mucosa of the vagina contains large amounts of glycogen that on decomposition, produces organic acids such as lactic acid. These acids function to create a low pH in the vagina that retards microbial growth. These also are injurious to sperm cells, therefore buffering action of the semen is important to neutralize the acidity of the vagina.
A fold of vaginal mucosa called the hymen partially blocks the vaginal entrance. The hymen is usually ruptured during the female’s first sexual intercourse, but it may be broken earlier during other physical activities or by the insertion of a tampon.
4. Physiology of the Female Reproductive System
4.1 Egg Cell Production (Oogenesis)
The production of egg cells begins in the ovaries of the fetus before birth, but the final development of the individual egg is only completed in adult life and is only fertilization occurs. Gamete production in males begins at puberty and continues throughout life, but the situation is quite different in females. A female’s total supply of eggs is already determined by the time she is born and the time span during which she releases them extends from puberty to menopause (about age 50). Meiosis, the specialized nuclear division that occurs in the testes to produce sperm also occurs in ovaries. In this case, female sex cells are produced, and the process is called oogenesis and takes years to complete.
Beginning at puberty, a small number of primary oocytes are activated each month. However, only one is selected to continue meiosis I, ultimately producing 2 haploid cells (each with 23 replicated chromosomes) that are quite dissimilar in size. The smaller cell is called the first polar body and the larger cell, which contains nearly all the cytoplasm of the primary oocyte, is the secondary oocyte. The events of this first maturation division are interesting. A spindle forms at the very edge of the oocyte and a little nipple into which the polar body chromosomes will be casted, appears at that edge. This sets up the polarity of the oocyte and ensures that the polar body receives almost mo cytoplasm and organelles. The first polar body usually undergoes meiosis II, producing 2 even smaller polar bodies. However, in humans, the secondary oocyte arrests in metaphase II and it is this cell that is ovulated.
There are some end products of oogenesis. There are the 3 tiny polar bodies (nearly devoid of cytoplasm) and one large ovum. All the cells are haploid, but only the ovum is a functional gamete. This differs from spermatogenesis where meiosis produces 4 viable spermatozoa.
The unequal divisions of cytoplasm that occur during oogenesis assure that a fertilized egg has ample nutrients for its seven day journey to the uterus. Without nutrient-containing cytoplasm, the polar bodies degenerate and die. Since he reproductive life of a female is best about 45 years (from age 11 to 55), and typically only one ovulation occurs each month, only 400 to 500 oocytes out of her potential of 700,000 are released during a woman’s lifetime. Again, nature has provided us with a generous oversupply of sex cells.
4.2 The Ovarian Cycle
It is a monthly series of events associated with the maturation of an egg. The ovarian cycle is best described in terms of 2 consecutive phases. The typical ovarian cycle repeats itself at intervals of 28 days, with ovulation occurring mid-cycle. However, cycles as long as 40 days or as short as 21 days are not uncommon. In such cases, the length of the follicular phase and timing of ovulation vary, but the luteal phase remains constant. It is 14 days between the time of ovulation and the end of the cycle. Hormonal control of these events will be considered shortly; here we will concentrate on what happens each month within the ovary.
4.2.1 The Follicular Phase
Maturation of the primordial follicle to the mature state occupies the first half of the cycle and involves several events as follows.
4.2.1.1 Formation of Primary Follicles
When the primordial follicles are activated, the squamous-like cells surrounding the primary oocyte grow to become cuboidal cells and the oocyte enlarges. The follicle is now called a primary follicle.
4.2.1.2 Formation of Secondary Follicles
Next, the follicular cells proliferate until they form a stratified epithelium around the oocyte. As soon as more than one cell layer is present, the follicle cells take on the name of granulose cells.
In the next stage, a layer of connective tissue begins to condense around the follicle, forming the theca folliculi. As the granulose cells continue to divide and the follicle grows, the thecal and granulose cells cooperate to produce estrogens (the inner thecal cells produce androgens while the granulose cells convert them to estrogens). At the same time, the granulose cells secrete a glycoprotein rich substance that forms a thick transparent membrane, called the zona pellucida around the oocyte.
In the next phase, clear liquid accumulates between the granulose cells and eventually coalesces to form a fluid-filled cavity called the antrum. The presence of an antrum distinguishes the new secondary follicle from the primary one.
4.2.1.3 Formation of a Tertiary Graafian Follicle
The antrum continues to expand with fluid until it isolates the oocyte, along with its surrounding capsule of granulose cells called the corona radiate, on a stalk on one side of the follicle.
When a follicle attains full size, it becomes a Graafian follicle and bulges from the external ovarian surface. This has usually occurred by day 14. As one of the final events of follicle maturation, the primary oocyte completes meiosis I to form the secondary oocyte and the first polar body. Once this has occurred, the stage is set for ovulation.
4.2.2 Ovulation
Ovulation occurs when the ovary wall rupture and expels the secondary oocyte (still surrounded by its corona radiate) into the peritoneal cavity. Some women experience abdominal pain in the lower abdomen when ovulation occurs. This phenomenon, called mettelschmerz, is thought to be caused by the intense stretching of the ovarian wall during ovulation.
In the ovaries of adult females, there are always several follicles at different stages of maturation. As a rule, one follicle outstrips the others to become the dominant follicle and is at the peak stage of maturation when the hormonal (LH) stimulus is given for ovulation. How this follicle is selected, or selects itself, is still uncertain. The others degenerate.
In 1% to 2% of all ovulations, more than one oocyte is ovulated, which can result in multiple births, since different oocytes are fertilized by different sperms, the siblings are fraternal or non-identical twins. Identical twins result from the fertilization of a single oocyte by a single sperm, followed by the separation of the fertilized egg’s daughter cells.
4.2.3 Luteal Phase
After ovulation and discharge of antrum fluid, the ruptured follicle collapses and the antrum is filled with clotted blood (the corpus hemorrhagicum) which is eventually absorbed. The remaining granulose cells increase in size and along with the internal thecal cells, they form a new, endocrine gland, the corpus luteum. Once formed, the corpus luteum begins to secrete progesterone and some estrogen
If no pregnancy occurs, the corpus luteum begins to degenerate in about 10 days and its hormonal output ceases. In this case, all that ultimately remains is a scar called corpus albicans.
On the other hand, if the oocyte is fertilized and pregnancy ensues, the corpus luteum persists until the placenta is ready to take over its hormone producing duties in about 3 months.
4.3 The Female Hormones: Estrogens and Progesterone
4.3.1 Estrogens
The naturally occurring estrogens are 17 beta-estradiol, estrone and estriol, collectively known as estrogens. They are all steroid hormones. They are secreted by the theca interna and granulose cells of the ovarian follicles, by the corpus luteum and by the placenta. 17 beta-estradiol is the major secreted estrogen and is in equilibrium in the circulation of estrone. Estrone is further metabolized to estriol, probably mainly in the liver. Estradiol is the most potent estrogen of the 3 and estriol is the least.
Most actions of estrogens on their target cells, like those of other steroid hormones, involve the entry of the steroid into the cell. This includes: binding to a receptor, which in the case of estrogen is in the nucleus; transformation of the receptor to expose a DNA-binding domain; and binding of the steroid-receptor complex to the DNA. This increases the transcription of certain genes with the production of mRNAs. The mRNAs code for proteins that bring about changes in cell function.
4.3.2 Progesterone
Progesterone is a steroid hormone secreted in large amounts by the corpus luteum and the placenta. It is an important intermediate in steroid biosynthesis in all tissues that secrete steroid hormones and small amounts enter circulation from the testes and adrenal cortex. It si synthesized in the female in the ovarian follicles and corpus luteum. Progesterone has a short half-life and is converted in the liver and excreted in the urine. The principle target organs are the uterus, the breasts and the brain. It is responsible for the progestational changes in the endometrium and the cyclical changes in the cervix and the vagina. It has anti-estrogenic effects on the myometrial cells, decreasing their excitability, their sensitivity to oxytocin.
Progesterone is thermogenic and is probably responsible for the rise in the basal body temperature at the time of ovulation. The effects of progesterone, like those of other steroids, are brought about by an action on DNA to initiate synthesis of new mRNA. Substances that mimic the action of progesterone are sometimes called progestational agents, gestagens or progestins. They are used along with synthetic estrogens as oral contraceptive agents.
4.4 Hormonal Regulation of the Ovarian Cycle
Ovarian events are much more complicated than those occurring within the testes, but the hormonal controls set into motion at puberty are quite similar in the 2 sexes. Gonadotropin-releasing hormone (GnRH), the pituitary gonadotropins and in this case, ovarian estrogen and progesterone interact to produce the cyclic events occurring in the ovaries.
4.4.1 Establishment of the Ovarian Cycle
During childhood, the ovaries grow and continuously secrete small amounts of estrogen which inhibit hypothalamic release of GnRH. But as puberty nears, the hypothalamus becomes less sensitive to estrogen and begins to release GnRH in a rhythmic pulse-like manner. GnRH in turn stimulates the anterior pituitary to release FSH and LH, which act on the ovaries.
Gonadotropin levels continue to increase for about 4 years, and during this time, the pubertal girl is anovulatory and hence incapable of becoming pregnant. Eventually, the adult cyclic pattern is achieved, and hormonal interactions stabilize. These events are heralded by the young woman’s first menstrual period referred to as menarche. Many cycles are still anovulatory in the one to two years that follow. Usually, it is not until the 3rd year post-menarche that the cycle becomes regular.
4.4.2 Hormonal Interactions during the Ovarian Cycle
The waxing and waning of the anterior pituitary gonadotropins (FSH and LH) and ovarian hormones and the positive and negative feedback interactions that regulate ovarian function appear to be described next. A 28-day cycle is assumed.
On day 1 of the cycle, rising levels of GnRH from the hypothalamus simulate the increased production and release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) by the anterior pituitary.
FSH and LH stimulate follicular growth and maturation and estrogen secretion. FSH exerts its main effects on the follicle cells, whereas LH (at least initially) more specifically targets the theca cells. (Why only some follicles respond to these hormonal stimuli is still a mystery. However, there is little doubt that enhanced responsiveness reflects the development of increased numbers of gonadotropin receptors).
As the follicles enlarge, estrogen secretion begins. LH prods the thecal cells to produce androgens. These diffuse through the basement membrane, where that are converted to estrogens by the FSH-primed granulose cells. Only tiny amounts of ovarian androgens enter the blood, because they are almost completely converted to estrogens within the ovaries.
The rising levels of estrogen in the plasma exert negative feedback on the anterior pituitary, inhibiting its release of FSH and LH, while simultaneously prodding it to synthesize and accumulate these gonadotropins. Within the ovary, estrogen increases the output of estrogens by intensifying the effect of FSH on follicle growth and maturation. Inhibin, released by the granulose cells, also exerts negative feedback controls of FSH release during this period.
While the initial small rise in estrogen blood levels inhibits the hypothalamic-pituitary axis as just described, high estrogen levels have the opposite effect. Once estrogen reaches a critical concentration in the blood, it exerts positive feedback on the brain and the anterior pituitary.
The stimulatory effects of high estrogen levels set a cascade of events into motion. There is a sudden burst of accumulated LH (and to a lesser extent FSH) by the anterior pituitary. This occurs about mid-cycle.
The sudden flush of LH stimulates the primary oocyte of the dominant follicle to complete its first meiotic division. The secondary oocyte formed continues on to metaphase II. LH also triggers ovulation at around day 14. Perhaps LH induces the synthesis of proteolyric enzymes, but whatever the mechanism, the blood stops flowing through the externally protruding part of the follicle wall and then within 5 minutes, that region of the follicle wall bulges out, thins and oozes fluid and then abruptly ruptures. The role of FSH in this process is unknown. Shortly after ovulation, estrogen levels decline. This probably reflects the damage to the dominant estrogen-secreting follicle during ovulation.
The LH surge also promotes transformation of the ruptured follicle into a corpus luteum and stimulates the newly formed endocrine gland to produce progesterone and estrogen almost immediately after it is formed.
As progesterone and estrogen levels rise in the blood, the combination exerts a powerful negative feedback effect on the anterior pituitary release of FSH and LH. As gonadotropins decline, development of new follicles is inhibited and additional LH surges that might cause additional oocytes to be ovulated are prevented.
As LLH blood levels decline, the stimulus for corpus luteum activity ends, and the corpus luteum begins to degenerate. As goes the corpus luteum, so go the levels of ovarian hormones, and blood estrogen and progesterone levels drop sharply. (However, if implantation of an embryo has occurred, the activity of the corpus luteum is maintained by an LH-like hormone (human chorionic gonadotropin) released by the developing embryo).
A marked decline in ovarian hormones at the end of the cycle (days 26 – 28) ends their blockade of FSH and LH secretion, and the cycle starts anew.
4.5 The Uterine Cycle (a.k.a. Menstrual Cycle)
Although the uterus is the receptacle in which the young embryo implants and develops, it is receptive to implantation only for a very short period each month. Not surprisingly, this brief interval coincides exactly with the time when a developing embryo would normally begin implanting, approximately 7 days after ovulation.
The uterine / menstrual cycle is a series of cyclic changes that the uterine endometrium goes through, month after month, as it responds to changing levels of ovarian hormones in the blood. There are 3 phases of the uterine cycle: menses, proliferation and secretory. Notice that the menstrual and proliferative phases overlap the follicular stage and ovulation in the ovarian cycle and that the uterine secretory phase corresponds to the ovarian luteal phase.
4.5.1 Hormonal Regulation of the Uterine Cycle (Events of the 3 stages)
4.5.1.1 Menstrual Phase (Days 1 – 7)
In this phase, the uterus sheds all but the deepest part of its endometrium, (At the beginning of this stage, gonadotropins and ovarian hormones are at their lowest normal levels. Then, FSH levels begin to rise.) The thick functional layer of the endometrium detaches from the uterine wall, a process that is accompanied by bleeding for 3 – 5 days. The detached tissue and blood pass out through the vagina as the menstrual flow. By day 7, the growing ovarian follicles are starting to produce more estrogen.
4.5.1.2 Proliferative Phase (Days 7 – 14)
In this phase, the endometrium rebuilds itself. All the changes in the endometrium in the proliferative phase ate stimulated by estrogens. Under the influence of rising blood levels of estrogen, the basal layer of the endometrium generates a new functional layer called the stratum functionalis.
4.5.1.2.1 Functions of Estrogens
It causes the stratum functionalis to thicken by causing its uterine glands to be drawn out so that they can lengthen (but they do not convolute and secrete any fluid during this phase) and its spinal arteries to increase in number. Consequently, the endometrium once again becomes velvety, thick and well vascularized. Induced synthesis of progesterone receptors in the endometrial cells are starting, readying them for interaction with progesterone. Normally, the cervical mucus is thick and sticky, but rising estrogen levels cause it to thin (thinnest at the time of ovulation)) and become crystalline, forming channels that facilitate the passage of sperm into the uterus. Ovulation occurs in the ovary at the end of this stage (day 14) in response to the sudden release of LH from the anterior pituitary. LH also converts the ruptured follicle into a corpus luteum.
4.5.1.3 Secretory Phase (Days 15 – 28)
In this phase, the endometrium prepares for implantation of an embryo. All events of the secretory phase are caused by progesterone.
4.5.1.3.1 Functions of Progesterone
As its levels rise during the secretory phase when it is produced by the corpus luteum, it accounts for the differentiation of the stratum functionalis by acting on the estrogen-primed endometrium, causing arteries to elaborate and coil more tightly and converting the functional area to a secretory mucosa. The endometrium is supplied by 2 types of arteries, the superficial two-thirds of the endometrium that is shed during menstruation, stratum functionalis, is supplied by long, coiled spiral arteries, whereas the deep layer that is not shed is supplied by short, straight basilar arteries.
Differentiation of the stratum functionalis stimulates the uterine glands to enlarge, coil, become tortuous and begin secreting a clear fluid containing nutritious glycoproteins into the uterine cavity. These nutrients sustain the embryo until it has implanted in the blood-rich endometrial lining.
Progesterone also causes the cervical mucus to become viscous and thick again, forming the cervical plug, which blocks sperm entry and plays an important role in keeping the uterus private in the event an embryo has begun to implant. Together with rising estrogen levels, progesterone inhibits LH release by the anterior pituitary.
If fertilization has not occurred, the corpus luteum begins to degenerate towards the end of the secretory phase as LH blood levels decline. Progesterone levels fall, depriving the endometrium of hormonal support and the spiral arteries kink and go into spasms. Denied of oxygen and nutrients, the endometrial cells begin to die and their lysosomes rupture, the functional layer begins to self digest, setting the stage of menstruation to begin on day 28. The spiral arteries constrict one final time and then suddenly relax and open wide. As blood gushes into the weakened capillary beds, they fragment, causing the functional layer to slough off.
5. Premenstrual Syndrome (PMS)
5.1 What is PMS?
Premenstrual syndrome / tension is the name give to a group of physical and emotional symptoms that some women experience on a regular basis in relation to menstruation. It can also be defined as a symptom or collection of symptoms that occurs regularly in relation to the menstrual cycle, with the onset of symptoms 5 to 11 days before the onset of menses and resolution of symptoms with menses or shortly thereafter.
The symptoms occur monthly, generally within 7 to 14 days prior to menstruation. Symptoms may seem to worsen as menstruation approaches and subside at the onset or after several days of menstruation. A symptom-free phase usually occurs following menses.
5.2 Symptoms of PMS
There are physical symptoms. There may be bloating, breast tenderness, swelling of feet and ankles, fluid retention and weight gain, painful uterine cramps just before and during the first few days of menstruation. There may be headaches, food cravings, acne breakout, low energy or fatigue, palpitations, dizziness backaches and muscle pain.
There are also psychological and emotional symptoms. There may be mood swings, irritability, depression, aggressiveness or hostility, crying spells, difficulty concentrating and changes in libido.
5.3 Causes of PMS
An exact cause of PMS has not been identified. However, it may be related to social, cultural, biological and psychological factors. PMS can occur with apparently normal ovarian function. It is assumed that PMS is of hormonal origin. Some doctors believe that it is directly related to problems with the production and balance of progesterone and estrogen. Since it occurs in the few days before menstruation, it could be due to changes in the balance of progesterone and estrogen which decline at different rates at this time. It may also be due to progesterone deficiency.
In fact, it is not known why some women have severe symptoms, some have mild ones, while others have none. It is generally believed that PMS, migraine and depression stem from neuro-chemical changes within the brain. Hormonal factors, such as estrogen levels, had not been associated until recent studies.
Estrogen holds fluid and with increasing estrogen comes fluid retention: many women repost weight gains of 5 pounds pre-menstrually. Estrogen has a central neurologic effect: it can contribute to increased brain activity and even seizures. Estrogen can also contribute to retention of salt and a dip in blood sugar. PMS patients and migraineurs benefit from both salt and sugar restriction and a mild diuretic.
5.4 Prevention of PMS
Some of the lifestyle changes often recommended for the treatment of PMS may actually be useful in preventing symptoms from developing or getting worse. Regular exercise 3 to 5 times per week and a balanced diet may prove beneficial. Recognizing that the body might have different sleep requirements at different times during a women’s menstrual cycle, it is important to assure adequate rest.
5.5 Treatment of PMS
Treatment of PMS involves a remedy or a combination of remedies that work for each individual. Self-care methods include exercise and dietary measures mentioned previously under the prevention category. It is also important to maintain a daily diary or log to record the type, severity and duration of symptoms. A symptom diary should be kept for a minimum of 3 months in order to correlate symptoms with the menstrual cycle. The diary will greatly assist the health care provider not only in the accurate diagnosis of PMS, but also with the proposed treatment methods.
Nutritional supplements may be recommended. Vitamin B6, calcium and magnesium are commonly used. Prostaglandin inhibitors may be prescribed for women with significant pain, including headache, stomachache, menstrual cramping and breast tenderness. Diuretics may be prescribed for women found to have significant weight gain die to fluid retention. Psychiatric medications and or therapy may be used for women who exhibit moderate to severe degree of anxiety, irritability or depression. Hormonal therapy may include a trial on oral contraceptives which may either increase or decrease PMS symptoms. The use of progesterone vaginal suppositories during the second half of the menstrual cycle is still controversial.
Commonly prescribed medications for PMS include the following.
Non-steroidal anti-inflammatory drugs (NNSAIDs) are one class of medications. Taken before your period, NSAIDs can ease cramping and breast discomfort. Keep in mind that prolonged usage of NSAIDs can cause stomach bleeding or ulcers and can be dangerous if you have liver, kidney or heart problems.
Oral contraceptives are another class of drugs. These stop ovulation and stabilize hormonal swings, thereby offering relief from PMS symptoms.
Antidepressants can also be used. Selective serotonin reuptake inhibitors (SSRIs), which include fluoxetine, sertraline and venlafaxine have been successful in reducing PMS symptoms in 60% to 70% of women who take them. These drugs can be used in doses lower than those actually prescribed for depression and can be taken daily or during the week or two before menstruation.
6. Menopause and Hormonal Replacement Therapy (HRT)
6.1 What is Menopause?
It is the transition period in a woman’s life when the ovaries stop producing eggs, menstrual activity decreases and eventually ceases and the body decreases the production of female hormones, estrogen and progesterone.
6.2 Causes, Incidence and Risk Factors
Menopause is a natural event in a woman’s life that normally occurs between the ages of 40 and 55. During menopause, ovulation ceases, eliminating reproductive ability and menstruation becomes less frequent and eventually stops.
In some women, menstrual activity stops suddenly but it usually tapers off, both in amount and duration of flow, and frequently the periods become more closely or more widely spaced. This irregularity may last for 2 or 3 years before menstruation finally ceases.
The symptoms of menopause are caused by changes in estrogen levels. From age 35 onwards, the menstrual cycle becomes less consistent. Women may not ovulate every menstrual cycle. Therefore without eggs, estrogen and progesterone are not secreted. Too low levels of estrogens lead to failure to stimulate the uterine lining and menstruation ceases. Decline of estrogens and progesterone leads to negative feedback mechanism involving the hypothalamus and pituitary glands which produces larger and larger amounts of FSH and LH secretions. Hence, ovaries cannot respond consistently to the above leading to normal menstrual cycles interspersed by estrogen deficiency.
High levels of FSH and LH can disrupt a woman’s metabolism. After menopause, estrone takes over as the major estrogen. Instead of being produced in the ovary, it is produced now in the fat cells and muscles. Because it is not produced cyclically after menopause, the rate of its formation does not fluctuate in the way it did pre-menopausally. As estrone is biologically much less active than estradiol, it can manifest itself as a relative excess of male hormones. Therefore, the woman’s overall hormonal profile tends towards that of a man. A gradual decrease of estrogen allows the body to slowly adjust to the hormone change, but in some women, a sudden decrease in estrogen levels occurs, causing severe symptoms. This result is often seen when menopause is caused by surgical removal of the ovaries.
6.3 Prevention of Menopause
Menopause is a natural and expected part of a woman’s development and does not need to be prevented. However, there are ways (both medical and non-medical) to reduce or eliminate some of the symptoms that may accompany menopause.
6.4 Signs and Tests for Menopause
A pap smear may indicate changes in the vaginal lining (mucosa) caused by changes in estrogen levels. Blood and urine tests can be used to measure the levels of estrogen, progesterone and plasma estradiol and estrone (part of the reproductive steroid group).
6.5 HRT
To relieve the symptoms of menopause, doctors may prescribe post-menopausal hormone therapy. This can involve the use of either estrogen alone or with another hormone called progesterone, or progestin in its synthetic form. The 2 hormones normally help to regulate a woman’s menstrual cycle. Progestin is added to estrogen to prevent the overgrowth of cells lining the uterus. This overgrowth can lead to uterine cancer. If you haven’t had a hysterectomy, you’ll receive estrogen plus progestin therapy; is you has the above procedure, you will receive estrogen-only therapy. The hormones must be taken daily or on only certain days of the month.
They can also be taken in several ways, including orally, through a patch on their skin, as a cream or gel, or with an intrauterine device or vaginal ring. How the therapy is taken can depend on its purpose. For instance, a vaginal estrogen ring or cream can ease vaginal dryness, urinary leakage or vaginal or urinary infections, but does not relieve hot flushes.
Hormone therapy may cause side effects, such as bleeding, bloating, breast tenderness or enlargement, headaches, mood changes and nausea. Further, side effects vary by how the hormone is taken. For instance, a patch may cause irritation at the site where it is applied.
6.5.1 Types of Treatment for Menopause
When estrogen is given, it is called estrogen replacement therapy (ERT). However, the amount of estrogen medication prescribed is not enough to be truly a replacement, in fact, it is only a small fraction of the amount of estrogen that the ovary produces.
When the uterus is present, the natural progesterone that the body once produced must be replaced, sometimes with progesterone vaginal suppositories or progesterone tablets, but most often with labels of progestin. This is called progesterone replacement therapy.
For HRT, adding progesterone or progestin prevents any increase in the risk of uterine cancer from estrogen. When progesterone or progestin is added to estrogen, that is called HRT. Unfortunately, ERT and HRT are sometimes incorrectly used interchangeably contributing to confiussion.
HRT replaces both estrogen and progesterone. While estrogen helps minimize many menopausal symptoms, it also stimulates the growth of endometrial tissues, a risk factor for the development of cancer. Progesterone or progestin protects the uterine wall from tissue build up that occurs with ERT, effectively preventing cancer of the uterus. Progesterone also assists estrogen in maintaining bone mineral density. This contribution of estrogen and progesterone is the most widely prescribed therapy for woman who still have an intact uterus.
