The Female Reproductive System

The human female reproductive system (or female genital system) contains two main parts:

1. Uterus

o Hosts the developing fetus

o Produces vaginal and uterine secretions

o Passes the anatomically male sperm through to the fallopian tubes

2. Ovaries

o Produce the anatomically female egg cells.

o Produce and secrete estrogen and progesterone

These parts are internal; the vagina meets the external organs at the vulva, which includes the labia, clitoris, and
urethra. The vagina is attached to the uterus through the cervix, while the uterus is attached to the ovaries via the
fallopian tubes. At certain intervals, the ovaries release an ovum, which passes through the fallopian tube into the
uterus.

If, in this transit, it meets with sperm, the sperm penetrates and merges with the egg, fertilizing it. The fertilization
usually occurs in the oviducts, but can happen in the uterus itself. The zygote then implants itself in the wall of the
uterus, where it begins the process of embryogenesis and morphogenesis. When developed enough to survive outside
the womb, the cervix dilates and contractions of the uterus propel the fetus through the birth canal (vagina).

The ova are larger than sperm and have formed by the time an anatomically female infant is born. Approximately every
month, a process of oogenesis matures one ovum to be sent down the fallopian tube attached to its ovary in
anticipation of fertilization. If not fertilized, this egg is flushed out of the system through menstruation.

An anatomically female’s internal reproductive organs are the vagina, uterus, fallopian tubes, cervix, and ovary.
The external components include the mons pubis, pudendal cleft, labia majora, labia minora, Bartholin’s glands, and
clitoris.

Female Repro: Illustrated sagittal view of the female reproductive system.

Ovaries

The ovary is an ovum-producing reproductive organ, typically found in pairs as part of the vertebrate female
reproductive system. Ovaries in females are analogous to testes in males in that both are gonads and endocrine glands.
Ovaries secrete both estrogen and progesterone. Estrogen is responsible for the appearance of secondary sex
characteristics of females at puberty and for the maturation and maintenance of the reproductive organs in their
mature functional state. Progesterone functions with estrogen by promoting menstrual cycle changes in the
endometrium.

Anatomical Features

The ovaries are located in the lateral wall of each side of the pelvis in a region called the ovarian fossa. The fossa usually
lies beneath the external iliac artery and in front of the ureter and internal iliac artery.

In humans, the paired ovaries lie within the pelvic cavity on either side of the uterus, to which they are attached via a
fibrous cord called the ovarian ligament. The ovaries are tethered to the body wall via the suspensory ligament of the
ovary. The part of the broad ligament of the uterus that covers the ovary is known as the mesovarium. The ovary is the
only organ in the human body which is totally invaginated into the peritonium, making it the only intraperitoneal organ.

There are two extremities to the ovary, the tubal extremity and the uterine extremity. The tubal extremity is the end to
which the Fallopian tube attaches via the infundibulopelvic ligament. The uterine extremity points downward and is
attached to the uterus via the ovarian ligament.

Ovary: A pictorial illustration of the female reproductive system

Physiology and Function

The ovaries are the site of egg cell production and also have specific endocrine function.

Oogenesis

The ovaries are the site of gamete (egg cell, oocyte) production. The developing egg cell (or oocyte) grows within the
environment provided by ovarian follicles. Follicles are composed of different types and number of cells according to
their maturation stage, which can be determined by their size. When oocyte maturation is completed, a luteinizing
hormone ( LH ) surge secreted by the pituitary gland stimulates follicle rupture and oocyte release.

This oocyte development and release process is referred to as ovulation. The follicle remains functional and transforms
into a corpus luteum, which secretes progesterone to prepare the uterus for possible embryo implantation. Usually each
ovary takes turns releasing eggs each month. However, this alternating egg release is random. When one ovary is absent
or dysfunctional, the other ovary will continue to release eggs each month.

Endocrine Function

Ovaries secrete estrogen, progesterone, and testosterone. Estrogen is responsible for the secondary sex characteristics
of females at puberty. It is also crucial for the maturation and maintenance of the mature and functional reproductive
organs. Progesterone prepares the uterus for pregnancy and the mammary glands for lactation. The co-actions of
progesterone and estrogen promote menstrual cycle changes in the endometrium. In women, testosterone is important
for the development of muscle mass, muscle and bone strength, and for optimal energy level. It also has a role in libido
in women.

Uterus

The uterus or womb is a major female hormone -responsive reproductive sex organ of most mammals including
humans. One end, the cervix, opens into the vagina, while the other is connected to one or both fallopian tubes,
depending on the species. It is within the uterus that the fetus develops during gestation, usually developing completely
in placental mammals such as humans.

Two Müllerian ducts usually form initially in a female fetus and, in humans, they completely fuse into a single uterus
depending on the species. The uterus consists of a body and a cervix. The cervix protrudes into the vagina. The uterus is
held in position within the pelvis by condensations of endopelvic fascia, which are called ligaments. These ligaments
include the pubocervical, transverse, cervical, cardinal, and uterosacral ligaments. It is covered by a sheet-like fold of
peritoneum, the broad ligament.

The uterus is essential in sexual response by directing blood flow to the pelvis and to the external genitalia, including the
ovaries, vagina, labia, and clitoris. The reproductive function of the uterus is to accept a fertilized ovum which passes
through the utero-tubal junction from the fallopian tube. It implants into the endometrium, and derives nourishment
from blood vessels which develop exclusively for this purpose.
 Uterus: Vessels of the uterus and its appendages, rear view.

The fertilized ovum becomes an embryo, attaches to a wall of the uterus, creates a placenta, and develops into a fetus
(gestates) until childbirth. Due to anatomical barriers such as the pelvis, the uterus is pushed partially into the abdomen
due to its expansion during pregnancy. Even during pregnancy, the mass of a human uterus amounts to only about a
kilogram (2.2 pounds).

The uterus is located inside the pelvis immediately dorsal (and usually somewhat rostral) to the urinary bladder and
ventral to the rectum. The human uterus is pear-shaped and about three inches (7.6 cm) long. The uterus can be divided
anatomically into four segments: The fundus, corpus, cervix and the internal os.

Ovary: A pictorial illustration of the female reproductive system.

The uterus is in the middle of the pelvic cavity in frontal plane (due to ligamentum latum uteri). The fundus does not
surpass the linea terminalis. The fundus of the uterus is the top, rounded portion, opposite from the cervix. The vaginal
part of the cervix does not extend below interspinal line. The uterus is mobile and moves under the pressure of the full
bladder or full rectum anteriorly, whereas if both are full it moves upwards. Increased intra-abdominal pressure pushes
it downwards. The mobility is conferred to it by musculo-fibrous apparatus that consists of a suspensory and
sustentacular part. Under normal circumstances the suspensory part keeps the uterus in anteflexion and anteversion (in
90% of women) and keeps it “floating” in the pelvis. In cases where the uterus is “tipped,” also known as retroverted
uterus, women may have symptoms of pain during sexual intercourse, pelvic pain during menstruation, minor
incontinence, urinary tract infections, difficulty conceiving, and difficulty using tampons. A pelvic examination by a
doctor can determine if a uterus is tipped.

The lining of the uterine cavity is called the endometrium. It consists of the functional endometrium and the basal
endometrium from which the former arises. Damage to the basal endometrium results in adhesion formation and/or
fibrosis (Asherman’s syndrome). In all placental mammals, including humans, the endometrium builds a lining
periodically which is shed or reabsorbed if no pregnancy occurs. Shedding of the functional endometrial lining is
responsible for menstrual bleeding (known colloquially as a “period” in humans, with a cycle of approximately 28 days,
+/- 7 days of flow and +/- 21 days of progression) throughout the fertile years of a female and for some time beyond.

Depending on the species and attributes of physical and psychological health, weight, environmental factors of circadian
rhythm, photoperiodism (the physiological reaction of organisms to the length of day or night), the effect of menstrual
cycles to the reproductive function of the uterus is subject to hormone production, cell regeneration, and other
biological activities. The menstrual cycles may vary from a few days to six months, but can vary widely even in the same
individual, often stopping for several cycles before resuming.

The uterus mostly consists of smooth muscle, known as myometrium. The innermost layer of myometrium is known as
the junctional zone, which becomes thickened in adenomyosis. The parametrium is the loose connective tissue around
the uterus. The perimetrium is the peritoneum covering of the fundus and ventral and dorsal aspects of the uterus. The
uterus is primarily supported by the pelvic diaphragm, perineal body, and the urogenital diaphragm. Secondarily, it is
supported by ligaments and the peritoneum (broad ligament of uterus).

Female Duct System

The Fallopian tubes, also known as oviducts, uterine tubes, and salpinges (singular salpinx), are two very fine tubes lined
with ciliated epithelia, leading from the ovaries of female mammals into the uterus via the uterotubal junction. In non-
mammalian vertebrates, the equivalent structures are the oviducts. These tubes allows passage of the egg from the
ovary to the uterus.

The different segments of the fallopian tube are ( lateral to medial):

 The infundibulum with associated fimbriae near the ovary

 The ampullary region that represents the major portion of the lateral tube

 The isthmus, which is the narrower part of the tube that links to the uterus

 The interstitial (intramural) part that transverses the uterine musculature

The tubal ostium is the point at which the tubal canal meets the peritoneal cavity, while the uterine opening of the
Fallopian tube is the entrance into the uterine cavity, the uterotubal junction.
Uterine Segments: Illustrative drawing of the anterior view of the uterus showing the uterine segments

There are two types of cells within the simple columnar epithelium of the Fallopian tube. Ciliated cells predominate
throughout the tube, but are most numerous in the infundibulum and ampulla. Estrogen increases the production of
cilia on these cells.

Interspersed between the ciliated cells are peg cells, which contain apical granules and produce the tubular fluid. This
fluid contains nutrients for spermatozoa, oocytes, and zygotes. The secretions also promote capacitation of the sperm
by removing glycoproteins and other molecules from the plasma membrane of the sperm. Progesterone increases the
number of peg cells, while estrogen increases their height and secretory activity. Tubal fluid flows against the action of
the ciliae, toward the fimbrated end.

When an ovum is developing in an ovary, it is encapsulated in a sac known as an ovarian follicle. On maturation, the
follicle and the ovary’s wall rupture, allowing the ovum to escape. The egg is caught by the fimbriated end and travels to
the ampulla where typically the sperm are met and fertilization occurs. The fertilized ovum, now a zygote, travels
towards the uterus aided by the tubal cilia and tubal muscle. After about five days, the new embryo enters the uterine
cavity and implants about a day later. Occasionally, the embryo implants into the Fallopian tube instead of the uterus,
creating an ectopic pregnancy.

Vagina

The vagina, a female sex organ, is a fibromuscular tubular tract that has two main functions: sexual intercourse and
childbirth. In humans, this passage leads from the opening of the vulva to the uterus, but the vaginal tract ends at the
cervix.

Anatomy of the Vagina

The vaginal opening is much larger than the urethral opening. During arousal, the vagina gets moist to facilitate the
entrance of the penis. The inner texture of the vagina creates friction for the penis during intercourse.

The vaginal opening is at the caudal end of the vulva behind the opening of the urethra. The upper quarter of the vagina
is separated from the rectum by the rectouterine pouch. The vagina and the inside of the vulva are a reddish-pink color,
as are most healthy internal mucous membranes in mammals. A series of ridges produced by the folding of the wall of
the outer third of the vagina is called the vaginal rugae. These transverse epithelial ridges and provide the vagina with
increased surface area for extension and stretching.

Vaginal lubrication is provided by the Bartholin’s glands near the vaginal opening and the cervix. The membrane of the
vaginal wall also produces moisture, although it does not contain any glands. Before and during ovulation, the cervix’s
mucus glands secrete different variations of mucus, which provides an alkaline environment in the vaginal canal that is
favorable to the survival of sperm.

The hymen is a membrane of tissue that surrounds or partially covers the external vaginal opening. The tissue may or
may not be ruptured by vaginal penetration. It can also be ruptured by childbirth, a pelvic examination, injury, or sports.
The absence of a hymen may not indicate prior sexual activity. Similarly, its presence may not indicate a lack of prior
sexual activity.

Function of the Vagina

The vagina’s primary functions are sexual arousal and intercourse as well as childbirth.

Sexual Arousal and Intercourse

The concentration of the nerve endings close to the entrance of a woman’s vagina (the lower third) can provide
pleasurable sensation during sexual activity when stimulated. Ninety percent of the vagina’s nerve endings are in this
area. However, the vagina as a whole has insufficient nerve endings for sexual stimulation and orgasm; this lack of nerve
endings makes childbirth significantly less painful.

Research indicates that clitoral tissue extends considerably into the vulva and vagina. During sexual arousal, and
particularly clitoral stimulation, the vaginal walls lubricate to reduce friction caused by sexual activity. With arousal, the
vagina lengthens rapidly to an average of about 4 in. (10 cm), and can continue to lengthen in response to pressure. As
the woman becomes fully aroused, the vagina tents (expands in length and width), while the cervix retracts. The walls of
the vagina are composed of soft elastic folds of mucous membrane which stretch or contract (with support from pelvic
muscles) to the size of the inserted penis or other object, stimulating the penis and helping the male to experience
orgasm and ejaculation, thus enabling fertilization.

An erogenous zone commonly referred to as the G-Spot (also known as the Gräfenberg Spot) is located at the anterior
wall of the vagina, about five centimeters in from the entrance. Some women experience intense pleasure if the G-Spot
is stimulated appropriately during sexual activity. A G-Spot orgasm may be responsible for female ejaculation, leading
some doctors and researchers to believe that G-Spot pleasure comes from the Skene’s glands, a female homologue of
the prostate, rather than any particular spot on the vaginal wall. Other researchers consider the connection between the
Skene’s glands and the G-Spot to be weak. They contend that the Skene’s glands do not appear to have receptors for
touch stimulation and that there is no direct evidence for their involvement. The G-Spot’s existence as a distinct
structure, is still under dispute, as its location can vary from woman to woman and is sometimes nonexistent.

The Vagina and Childbirth

The vagina provides the channel to deliver the baby from the uterus to its independent life outside the mother’s body.
During birth, the elasticity of the vagina allows it to stretch to many times its normal diameter. The vagina is often
referred to as the birth canal in the context of pregnancy and childbirth.

Vulva

The vulva consists of the external genital organs of the female. Its development occurs during several phases, chiefly
during the fetal and pubertal periods.

As the outer portal of the human uterus or womb, the vulva protects its opening with a “double door”: the labia majora
(large lips) and the labia minora (small lips). The vulva also contains the opening of the female urethra, and thus serves
the vital function of passing urine.

Major structures of the vulva are:

 The mons pubis

 The labia majora and the labia minora

 The external portion of the clitoris and the clitoral hood

 The vulval vestibule

 The pudendal cleft

 The frenulum labiorum pudendi or fourchette

 The opening (or urinary meatus) of the urethra

 The opening (or introitus) of the vagina

 The hymen

Other notable structures include:

 The perineum

 The sebaceous glands on labia majora

 The vaginal glands (Bartholin’s glands and paraurethral or Skene’s, glands)

The soft mound at the front of the vulva, the mons pubis, is formed by fatty tissue covering the pubic bone. The mons
pubis separates into two folds of skin called the labia majora, literally “major (or large) lips.” The cleft between the labia
majora is called the pudendal cleft, or cleft of Venus, and it contains and protects the other, more delicate structures of
the vulva. The labia majora meet again at the perineum, a flat area between the pudendal cleft and the anus. The color
of the outside skin of the labia majora is usually close to the individual’s overall skin color although there is considerable
variation.

The inside skin and mucus membrane are often pink or brownish. After the onset of puberty, the mons pubis and the
labia majora become covered by pubic hair. This hair sometimes extends to the inner thighs and perineum, but the
density, texture, color, and extent of pubic hair coverage vary considerably due to both individual variation and cultural
practices of hair modification or removal. The labia minora are two soft folds of skin within the labia majora.

The clitoris is located at the front of the vulva where the labia minora meet. The visible portion of the clitoris is the
clitoral glans, roughly the size and shape of a pea. The clitoral glans is highly sensitive, containing as many nerve endings
as the analogous organ in males, the glans penis. The point where the labia minora attach to the clitoris is called the
frenulum clitoridis. A prepuce, the clitoral hood, normally covers and protects the clitoris; however, in women with
particularly large clitorises or small prepuces, the clitoris may be partially or wholly exposed. The clitoral hood is the
female equivalent of the male foreskin and may be partially hidden inside of the pudendal cleft.

The area between the labia minora is called the vulval vestibule, and it contains the vaginal and urethral openings. The
urethral opening (meatus) is located below the clitoris and just in front of the vagina. This is where urine passes from the
urinary bladder.

The opening of the vagina is located at the bottom of the vulval vestibule toward the perineum. The term introitus is
more technically correct than “opening,” since the vagina is usually collapsed, with the opening closed unless something
is inserted. The introitus is sometimes partly covered by a membrane called the hymen. The hymen will rupture during
the first episode of vigorous sex, and the blood produced by this rupture has been traditionally seen as a sign of virginity.
However, the hymen may also rupture spontaneously during exercise or be stretched by normal activities such as use of
tampons. Slightly below and to the left and right of the vaginal opening are two Bartholin glands which produce a waxy,
pheromone-containing substance, the purpose of which is not yet fully known.
Perineum

In human anatomy, the perineum is the surface region between the pubic symphysis and coccyx in both males and
females, including the perineal body and surrounding structures. The boundaries vary in classification but generally
include the genitals and anus. It is an erogenous zone for both males and females.

Perineum Illustration: Illustrated drawing of the muscles of the female perineum.

The term perineum may refer to only the superficial structures in this region or be used to include both superficial and
deep structures. The term lower rabbus is used colloquially in the UK to describe this structure. Perineal tears and
episiotomy often occur in childbirth with first-time deliveries, but the risk of these injuries can be reduced by preparing
the perineum through massage.

The perineum corresponds to the outlet of the pelvis. Its deep boundaries are:

 The pubic arch and the arcuate ligament of the pubis

 The tip of the coccyx

 he inferior rami of the pubis and ischial tuberosity, and the sacrotuberous ligament

The perineum includes two distinct regions separated by the pelvic diaphragm. Its structures include:

 Superficial and deep perineal pouches

 Ischioanal fossa, a fat-filled space at the lateral sides of the anal canal bounded laterally by obturator internus
muscle, medially by pelvic diaphragm and the anal canal.
  Anal canal

 Pudendal canal, which contains internal pudendal artery and the pudendal nerve

Mammary Glands

A mammary gland is an organ in female mammals that produces milk to feed young offspring.

Anatomy of the Mammary Gland

The basic components of a mature mammary gland are the alveoli, hollow cavities, a few millimeters large lined with
milk-secreting cuboidal cells and surrounded by myoepithelial cells. These alveoli join to form groups known as lobules,
and each lobule has a lactiferous duct that drains into openings in the nipple. The myoepithelial cells can contract under
the stimulation of oxytocin, excreting milk secreted from alveolar units into the lobule lumen toward the nipple where it
collects in sinuses of the ducts. As the infant begins to suck, the hormonally (oxytocin) mediated “let-down reflex”
ensues, and the mother’s milk is secreted into the baby’s mouth.

Mammary Gland: Cross-section of the mammary-gland. 1. Chest wall 2. Pectoralis muscles 3. Lobules 4. Nipple 5.
Areola 6. Milk duct 7. Fatty tissue 8. Skin EndFragment

All the milk-secreting tissue leading to a single lactiferous duct is called a simple mammary gland; a complex mammary
gland is all the simple mammary glands serving one nipple. Humans normally have two complex mammary glands, one
in each breast, and each complex mammary gland consists of 10–20 simple glands. The presence of more than two
nipples is known as polythelia, and the presence of more than two complex mammary glands as polymastia.
Development of the Mammary Glands

Mammary glands develop during different growth cycles. They exist in both sexes during the embryonic stage, forming
only a rudimentary duct tree at birth. In this stage, mammary gland development depends on systemic (and maternal)
hormones, but is also under the local regulation of paracrine communication between neighboring epithelial and
mesenchymal cells by parathyroid hormone-related protein. This locally-secreted factor gives rise to a series of outside-
in and inside-out positive feedback between these two types of cells, so that mammary bud epithelial cells can
proliferate and sprout down into the mesenchymal layer until they reach the fat pad to begin the first round of
branching.

Lactiferous duct development occurs in females in response to circulating hormones, first during pre- and postnatal
stages and later during puberty. Estrogen promotes branching differentiation, which is inhibited by testosterone in
males. A mature duct tree reaching the limit of the fat pad of the mammary gland is formed by bifurcation of duct
terminal end buds, secondary branches sprouting from primary ducts and proper duct lumen formation.

The Process of Milk Production

Secretory alveoli develop mainly in pregnancy, when rising levels of prolactin, estrogen, and progesterone cause further
branching, together with an increase in adipose tissue and a richer blood flow. In gestation, serum progesterone remains
at a high concentration so signaling through its receptor is continuously activated. As one of the transcribed genes, Wnts
secreted from mammary epithelial cells act paracrinely to induce branching of neighboring cells. When the lactiferous
duct tree is almost ready, alveoli are differentiated from luminal epithelial cells and added at the end of each branch. In
late pregnancy and for the first few days after giving birth, colostrum is secreted.

Milk secretion (lactation) begins a few days after birth, caused by reduction in circulating progesterone and the presence
of prolactin, which mediates further alveologenesis and milk protein production and regulates osmotic balance and tight
junction function.
The binding of laminin and collagen in the myoepithelial basement membrane with beta-1 integrin on the epithelial
surface insures correct placement of prolactin receptors on basal lateral side of alveoli cells and directional secretion of
milk into lactiferous ducts. Suckling of the baby causes release of hormone oxytocin which stimulates contraction of the
myoepithelial cells. With combined control from the extracellular matrix (ECM) and systemic hormones, milk secretion
can be reciprocally amplified to provide enough nutrition for the baby.

During weaning, decreased prolactin, lack of mechanical stimulation through suckling, and changes in osmotic balance
caused by milk stasis and leaking of tight junctions cause cessation of milk production. In some species there is complete
or partial involution of alveolar structures after weaning; however, in humans there is only partial involution, which
widely varies among individuals. Shrinkage of the mammary duct tree and ECM remodeling by various proteinase is
under the control of somatostatin and other growth-inhibiting hormones and local factors. This structure change leads
loose fat tissue to fill the empty space. However, a functional lactiferous duct tree can be reformed when a female is
pregnant again.

Physiology of the Female Reproductive System

Oogenesis

Oogenesis is the maturation of the female gametes through meiotic division.

The menstrual cycle begins with the maturation of oocytes through the process of oogenesis, as well as concurrent
follicle development that stimulates ovulation. Oogenesis starts with the process of developing oogonia via the
transformation of primordial follicles into primary oocytes, a process called oocytogenesis. Oocytogenesis is complete
either before or shortly after birth in humans. During the menstrual cycle primary oocytes complete maturation through
further meiotic divisions.
Follicle development signals the beginning of the menstrual cycle. At the start of the menstrual cycle, some 12-20
primary follicles begin to develop under the influence of elevated levels of follicle-stimulating hormone (FSH) to form
secondary follicles. The primary follicles form from primordial follicles, which develop in the ovary as a fetus during
conception and are arrested in the prophase state of the cellular cycle.

By around day 9 of the menstrual cycle, only one healthy secondary follicle remain. The rest are reabsorbed into the
ovary. The remaining follicle, called the dominant follicle, is responsible for producing large amounts of estrogen during
the late follicular phase.

On day 14 of the cycle, a luteinizing hormone surge is triggered by the positive feedback of estrogen. This causes the
secondary follicle to develop into a tertiary follicle, which then leaves the ovary 24–36 hours later. An important event in
the development of the tertiary follicle occurs when the primary oocyte completes the first meiotic division, resulting in
the formation of a polar body and a secondary oocyte. The empty follicle then forms a corpus luteum which later
releases progesterone to maintain a potential pregnancy.

Immediately after meiosis I, the haploid secondary oocyte initiates meiosis II. However, this process is also halted at the
metaphase II stage until fertilization occurs. When meiosis II has completed, an ootid and another polar body is created.

Both polar bodies disintegrate at the end of meiosis II, leaving only the ootid, which eventually develops into a mature
ovum. The formation of polar bodies serves to discard the extra haploid sets of chromosomes that have resulted as a
consequence of meiosis.
. Ovarian Cycle

The menstrual cycle is the physiological process that fertile women undergo for the purposes of reproduction and
fertilization.

The menstrual cycle is the scientific term for the physiological changes that occur in fertile women for the purpose of
sexual reproduction. The menstrual cycle is controlled by the endocrine system and commonly divided into three
phases: the follicular phase, ovulation, and the luteal phase. However, some sources define these phases as
menstruation, proliferative phase, and secretory phase. Menstrual cycles are counted from the first day of menstrual
bleeding.

The Follicular Phase

The follicular phase (or proliferative phase) is the phase of the menstrual cycle in humans and great apes during which
follicles in the ovary mature, ending with ovulation. The main hormone controlling this stage is estradiol. During the
follicular phase, follicle-stimulating hormone (FSH) is secreted by the anterior pituitary gland. FSH levels begin to rise in
the last few days of the previous menstrual cycle and peak during the first week of the follicular phase. The rise in FSH
levels recruits five to seven tertiary-stage ovarian follicles (also known as Graafian or antral follicles) for entry into the
menstrual cycle. These follicles compete with each other for dominance.

FSH induces the proliferation of granulosa cells in the developing follicles and the expression of luteinizing hormone (LH)
receptors on these granulosa cells. Two or three days before LH levels begin to increase, usually by day seven of the
cycle, one or occasionally two of the recruited follicles emerges as dominant. Many endocrinologists believe that
estrogen secretion of the dominant follicle increases to a level that indirectly lowers the levels of LH and FSH. This
slowdown in LH and FSH production leads to the atresia (death) of most of the recruited follicles, though the dominant
follicle continues to mature.

These high estrogen levels initiate the formation of a new layer of endometrium in the uterus. Crypts in the cervix are
also stimulated to produce fertile cervical mucus that reduces the acidity of the vagina, creating a more hospitable
environment for sperm. In addition, basal body temperature may lower slightly under the influence of high estrogen
levels. Ovulation normally occurs 30 (± 2) hours after the beginning of the LH surge (when LH is first detectable in urine).

Ovulation

Ovulation is the phase in which a mature ovarian follicle ruptures and discharges an ovum (also known as an oocyte,
female gamete, or egg). Ovulation also occurs in the estrous cycle of other female mammals, which differs in many
fundamental ways from the menstrual cycle. The time immediately surrounding ovulation is referred to as the ovulatory
phase or the periovulatory period.

The Luteal Phase

The luteal phase (or secretory phase) is the latter part of the menstrual or estrous cycle. It begins with the formation of
the corpus luteum and ends in either pregnancy or luteolysis. The main hormone associated with this stage is
progesterone, which is significantly higher during the luteal phase than in other phases of the cycle. Some sources define
the end of the luteal phase as a distinct ischemic phase.

After ovulation, the pituitary hormones FSH and LH cause the remaining parts of the dominant follicle to transform into
the corpus luteum. It continues to grow for some time after ovulation and produces significant amounts of hormones,
particularly progesterone, and to a lesser extent, estrogen. Progesterone plays a vital role in making the endometrium
receptive to implantation of the blastocyst and supportive of the early pregnancy. It also raises the woman’s basal body
temperature. The hormones produced by the corpus luteum suppress production of the FSH and LH, causing the corpus
luteum will atrophy. The death of the corpus luteum results in falling levels of progesterone and estrogen. This in turn
causes increased levels of FSH, leading to recruitment of follicles for the next cycle. Continued drops in estrogen and
progesterone levels trigger the end of the luteal phase, menstruation, and the beginning of the next cycle.
The loss of the corpus luteum can be prevented by implantation of an embryo. After implantation, human embryos
produce human chorionic gonadotropin (hCG), which is structurally similar to LH and can preserve the corpus luteum.
Because the hormone is unique to the embryo, most pregnancy tests look for the presence of hCG. If implantation
occurs, the corpus luteum will continue to produce progesterone (and maintain high basal body temperatures) for eight
to twelve weeks, after which the placenta takes over this function.

The ovarian cycle: The ovarian cycle is the series of changes that occur in the ovary during the menstrual cycle that
cause maturation of a follicle, ovulation, and development of the corpus luteum.

Uterine (Menstrual) Cycle

The uterine cycle describes a series of changes that occur to the lining of the uterus, or endometrium, during a typical
menstrual cycle.

Several changes to the uterine lining (endometrium) occur during the menstrual cycle, also called the uterine cycle. The
endometrium is the innermost glandular layer of the uterus. During the menstrual cycle, the endometrium grows to a
thick, blood vessel-rich tissue lining, representing an optimal environment for the implantation of a blastocyst upon its
arrival in the uterus. Menstrual cycles are counted from the first day of menstrual bleeding and are typically 28 days
long.

During menstruation, the body begins to prepare for ovulation again. The levels of estrogen gradually rise, signalling the
start of the follicular, or proliferation, phase of the menstrual cycle. The discharge of blood slows and then stops in
response to rising hormone levels and the lining of the uterus thickens, or proliferates. Ovulation is triggered by a surge
in luteinizing hormone. The sudden change in hormones at the time of ovulation sometimes causes minor changes in the
endometrium and light midcycle blood flow.

After ovulation, under the influence of progesterone, the endometrium changes to a secretory lining in preparation for
the potential implantation of an embryo to establish a pregnancy. If a blastocyst implants, then the lining remains as the
decidua. This becomes part of the placenta and provides support and protection for the embryo during gestation.

If implantation does not occur within approximately two weeks, the progesterone-producing corpus luteum in the ovary
will recede, causing sharp drops in levels of both progesterone and estrogen. This hormone decrease causes the uterus
to shed its lining and the egg in menstruation. The cessation of menstrual cycles at the end of a woman’s reproductive
period is termed menopause. The average age of menopause in women is 52 years, but it can occur anytime between 45
and 55.
The Uterine Cycle: High estrogen and progesterone levels stimulate increased endometrial thickness, but following their
decline from a lack of implantation, the endometrium is shed and menstruation occurs.

Normal menstrual flow can occur although ovulation does not occur. This is referred to as an anovulatory cycle.
Follicular development may start but not be completed although estrogen will still stimulate the uterine lining.
Anovulatory flow that results from a very thick endometrium caused by prolonged, continued high estrogen levels is
called estrogen breakthrough bleeding. However, if it is triggered by a sudden drop in estrogen levels, it is called
withdrawal bleeding. Anovulatory cycles commonly occur before menopause and in women with polycystic ovary
syndrome.

Hormonal Regulation of the Female Reproductive Cycle

The menstrual cycle is controlled by a series of changes in hormone levels, primarily estrogen and progesterone.

The menstrual cycle is the physiological change that occurs under the control of the endocrine system in fertile women
for the purposes of sexual reproduction and fertilization.

The Menstrual Cycle: The menstrual cycle is controlled by the endocrine system, with distinct phases correlated to
changes in hormone concentrations.

Phases of the Menstrual Cycle

The menstrual cycle is divided into three stages: follicular phase, ovulation, and the luteal phase.

Follicular Phase

During the follicular phase (or proliferative phase), follicles in the ovary mature under the control of estradiol. Follicle-
stimulating hormone (FSH) is secreted by the anterior pituitary gland beginning in the last few days of the previous
menstrual cycle. Levels of FSH peak during the first week of the follicular phase. The rise in FSH recruits tertiary-stage
ovarian follicles (antral follicles) for entry into the menstrual cycle.

Follicle-stimulating hormone induces the proliferation of granulosa cells in the developing follicles and the expression of
luteinizing hormone (LH) receptors on these cells. Under the influence of FSH, granulosa cells begin estrogen secretion.
This increased level of estrogen stimulates production of gonadotropin-releasing hormone (GnRH), which increases
production of LH. LH induces androgen synthesis by theca cells, stimulates proliferation and differentiation, and
increases LH receptor expression on granulosa cells.

Throughout the entire follicular phase, rising estrogen levels in the blood stimulate growth of the endometrium and
myometrium of the uterus. This also causes endometrial cells to produce receptors for progesterone, which helps prime
the endometrium to the late proliferative phase and the luteal phase. Two or three days before LH levels begin to
increase, one or occasionally two of the recruited follicles emerge as dominant. Many endocrinologists believe that the
estrogen secretion of the dominant follicle lowers the levels of LH and FSH, leading to the atresia (death) of most of the
other recruited follicles. Estrogen levels will continue to increase for several days.

High estrogen levels initiate the formation of a new layer of endometrium in the uterus, the proliferative endometrium.
Crypts in the cervix are stimulated to produce fertile cervical mucus that reduces the acidity of the vagina, creating a
more hospitable environment for sperm. In addition, basal body temperature may lower slightly under the influence of
high estrogen levels.

Ovulation

Estrogen levels are highest right before the LH surge begins. The short-term drop in steroid hormones between the
beginning of the LH surge and ovulation may cause mid-cycle spotting or bleeding. Under the influence of the
preovulatory LH surge, the first meiotic division of the oocytes is completed. The surge also initiates luteinization of
theca and granulosa cells. Ovulation normally occurs 30 (± 2) hours after the beginning of the LH surge.

Ovulation is the process in a female’s menstrual cycle by which a mature ovarian follicle ruptures and discharges an
ovum (oocyte). The time immediately surrounding ovulation is referred to as the ovulatory phase or the periovulatory
period. In the preovulatory phase of the menstrual cycle, the ovarian follicle undergoes cumulus expansion stimulated
by FSH. The ovum then leaves the follicle through the formed stigma. Ovulation is triggered by a spike in the amount of
FSH and LH released from the pituitary gland.

Luteal Phase

The luteal phase begins with the formation of the corpus luteum stimulated by FSH and LH and ends in either pregnancy
or luteolysis. The main hormone associated with this stage is progesterone, which is produced by the growing corpus
luteum and is significantly higher during the luteal phase than other phases of the cycle. Progesterone plays a vital role
in making the endometrium receptive to implantation of the blastocyst and supportive of the early pregnancy. It also
raises the woman’s basal body temperature.

Several days after ovulation, the increasing amount of estrogen produced by the corpus luteum may cause one or two
days of fertile cervical mucus, lower basal body temperatures, or both. This is known as a secondary estrogen surge. The
hormones produced by the corpus luteum suppress production of the FSH and LH, which leads to its atrophy. The death
of the corpus luteum results in falling levels of progesterone and estrogen, which triggers the end of the luteal phase.
Increased levels of FSH start recruiting follicles for the next cycle.

Alternatively, the loss of the corpus luteum can be prevented by implantation of an embryo: after implantation, human
embryos produce human chorionic gonadotropin (hCG). Human chorionic gonadotropin is structurally similar to LH and
can preserve the corpus luteum. Because the hormone is unique to the embryo, most pregnancy tests look for the
presence of hCG. If implantation occurs, the corpus luteum will continue to produce progesterone (and maintain high
basal body temperatures) for eight to 12 weeks, after which the placenta takes over this function.
Extrauterine Effects of Estrogens and Progesterone

Estrogen and progesterone have several effects beyond their immediate roles in the menstrual cycle, pregnancy, and
labor.

Both estrogens and progesterone serve functions in the body beyond their roles in menstruation, pregnancy, and
childbirth.

Estrogens Overview

Estradiol: One of the estrogens produced in the human body, predominant during a woman’s reproductive years.

Estrogens are a group of compounds named for their importance in the estrous cycle of humans and other animals. They
are the primary female sex hormones, although they are found in males as well. The three major naturally occurring
forms of estrogen in women are estrone (E1), estradiol (E2), and estriol (E3). Estetrol (E4) is produced only during
pregnancy.

Natural estrogens are steroid hormones, while some synthetic versions are non-steroidal. Estrogens are synthesized in
all vertebrates as well as some insects, and their presence in both suggests that they have an ancient evolutionary
history. Like all steroid hormones, estrogen readily diffuses across the cell membrane. Once inside the cell, it binds to
and activates estrogen receptors which in turn modulate the expression of many genes.

Functions of Estrogens

Estriol: Another one of the three main estrogens produced in humans.

While estrogens are present in both men and women, they are usually at significantly higher levels in women of
reproductive age. They promote the development of female secondary sexual characteristics, such as breasts, pubic
hair, and female fat distribution. They are also involved in the thickening of the endometrium and other aspects of
menstrual cycle regulation.

Other functions of and structural changes induced by estrogen include:

 Formation of female secondary sex characteristics

 Accelerating metabolism
  Increasing fat stores

 Stimulating endometrial growth

 Increasing uterine growth

 Increasing vaginal lubrication

 Thickening the vaginal wall

 Maintaining blood vessels and skin

 Reducing bone resorption, increasing bone formation

 Reducing muscle mass

Effect on Libido

Sex drive is dependent on androgen levels only in the presence of estrogen. Without estrogen, free testosterone levels
actually decrease sexual desire, as demonstrated in women who have hypoactive sexual desire disorder. The sexual
desire in these women can be restored by administration of estrogen through oral contraceptives.

Mental Health

Estrogen plays a significant role in women’s mental health. Sudden estrogen withdrawal, fluctuating estrogen, and
periods of sustained low levels of estrogen correlate with significant mood changes. Restoration or stabilization of
estrogen levels is clinically effective for recovery from postpartum, perimenopause, and postmenopause depression.

Progesterone Overview

Progesterone is a steroid hormone involved in the female menstrual cycle, pregnancy (supports gestation ), and
embryogenesis of humans and other species.

Progesterone belongs to a class of hormones called progestogens and is the major naturally-occurring human form in
this category. Progesterone exerts its primary action through the intracellular progesterone receptor, although a
distinct, membrane-bound progesterone receptor has also been postulated.

Functions of Progesterone

Progesterone has a number of physiological effects that are amplified in the presence of estrogen. Estrogen, through
estrogen receptors, upregulates the expression of progesterone receptors. Also, elevated levels of progesterone
potently reduce the sodium-retaining activity of aldosterone, resulting in natriuresis and a reduction in extracellular fluid
volume. Progesterone withdrawal, on the other hand, is associated with a temporary increase in sodium retention
(reduced natriuresis, with an increase in extracellular fluid volume) due to the compensatory increase in aldosterone
production. This combats the blockade of the mineralocorticoid receptor by the previously-elevated level of
progesterone.

Progesterone has key effects via non-genomic signalling on human sperm as they migrate through the female tract
before fertilization occurs, though the receptor(s) as yet remain unidentified. Detailed characterization of the events
occurring in sperm in response to progesterone has shed light on intracellular calcium transients, maintained changes,
and slow calcium oscillations, now thought to possibly regulate motility.

Progesterone is sometimes called the “hormone of pregnancy” and has many roles relating to fetal development. It
converts the endometrium to its secretory stage to prepare the uterus for implantation. At the same time, it affects the
vaginal epithelium and cervical mucus, making them thick and impenetrable to sperm.

If pregnancy does not occur, progesterone levels will decrease, leading to menstruation. Normal menstrual bleeding is
progesterone-withdrawal bleeding. If ovulation does not occur and the corpus luteum does not develop, its levels may
be low, leading to anovulatory dysfunctional uterine bleeding. During implantation and gestation, progesterone appears
to decrease the maternal immune response to allow for the acceptance of the pregnancy and decrease contractility of
the uterine smooth muscle.

In addition, progesterone inhibits lactation during pregnancy. A drop in its levels is facilitates the onset of labor. Another
drop following delivery is one of the triggers for milk production. The fetus metabolizes placental progesterone in the
production of adrenal steroids.

Female Sexual Response

Female sexual arousal causes physiological changes including increased blood flow to the genitals and enlargement and
lubrication of the vagina.

Sexual arousal is caused by sexual desire during or in anticipation of sexual activity. A number of physiological changes
occur in the body and mind in preparation for sex and continue during the act. For women, these changes include
increased blood flow to the nipples, vulva, clitoris, and vaginal walls, and increased vaginal lubrication.

Physiological Response

Features of the vulva: The clitoris and labial folds are labelled.

The beginnings of sexual arousal in a woman’s body is usually marked by vaginal lubrication, engorgement of the
external genitals, and internal enlargement of the vagina. Further stimulation can lead to more vaginal wetness and
further engorgement and swelling of the clitoris and the labia, along with increased redness or darkening of the skin in
these areas. Changes also occur to the internal shape of the vagina and to the position of the uterus within the pelvis.

Other bodily changes include an increase in heart rate and blood pressure, as well as flushing across the chest and upper
body. If sexual stimulation continues, then sexual arousal may peak into orgasm, resulting in rhythmic muscular
contractions in the pelvic region characterized by an intense sensation of pleasure. Experienced by males and females,
orgasms are controlled by the involuntary or autonomic nervous system.

As women age, estrogen levels decrease. Reduced estrogen levels may be associated with increased vaginal dryness and
less clitoral erection when aroused, but are not directly related to other aspects of sexual interest or arousal. In older
women, decreased pelvic muscle tone may prolong the time to reach orgasm, diminish the intensity of orgasms, and
cause more rapid resolution. In some women, the uterine contracts that occur during orgasm may cause pain or
discomfort.

Psychological Response

Mental and physical stimuli such as touch and the internal fluctuation of hormones influence sexual arousal. Cognitive
factors like sexual motivation, perceived gender role expectations, and sexual attitudes play important roles in women’s
self-reported levels of sexual arousal. Basson suggests that women’s need for intimacy prompts them to engage with
sexual stimuli, leading to an experience of sexual desire and psychological sexual arousal.

Research by Goldey and van Anders showed that sexual cognition impacts hormone levels in women. For instance,
sexual thoughts result in a rapid increase in testosterone in women who were not using hormonal contraception.
Inconsistent study results indicate that, although testosterone is involved in libido and sexuality of some women, its
effects can be obscured by the coexistence of psychological factors in others.