Female Physiology Before Pregnancy and Female Hormones pdf - Endocrinology and Reproduction

during different parts of the cycle. Figure 81–3 shows the approximate

female monthly sexual cycle; they are secreted at drastically differing rates

These various hormones are not secreted in constant amounts throughout the

progesterone,

3. The ovarian hormones,

2. The anterior pituitary sex hormones,

1. A hypothalamic releasing hormone,

of hormones, as follows:

The female hormonal system, like that of the male, consists of three hierarchies

Female Hormonal System

even these degenerate soon thereafter.

), only a few primordial follicles remain in the ovaries, and

). At the end of reproductive

each month; the remainder degenerate (become

age, 400 to 500 of the primordial follicles develop enough to expel their ova—one

During all the reproductive years of adult life, between about 13 and 46 years of

primary oocyte.

two more cell divisions before it can be fertilized by a sperm. At this time, the ovum

The ovum itself at this stage is still immature, requiring

primordial follicle.

The ovum surrounded by a single layer of granulosa cells is

granulosa cells.

the ovary) and causes them to take on epithelioid characteristics; they are then

lium and migrate into the substance of the ovarian cortex. Each ovum then collects

primordial ova

As the female fetus develops,

which embryologically is derived from the epithelium of the germinal ridges.

During fetal life, the outer surface of the ovary is covered by a

placenta, and fetal membranes—and eventually into a baby.

fertilized by a sperm, it implants in the uterus, where it develops into a fetus, a

ovum then passes through one of the fallopian tubes into the uterus; if it has been

the abdominal cavity near the open fimbriated ends of the two fallopian tubes. This

each monthly sexual cycle, a single ovum is expelled from an ovarian follicle into

Reproduction begins with the development of ova in the ovaries. In the middle of

ovaries, fallopian tubes, uterus,

tract, the most important of which are the

Figures 81–1 and 81–2 show the principal organs of the human female reproductive

Sexual Organs

nancy and childbirth.

with preparation of the female body for pregnancy,

period of pregnancy itself. This chapter is concerned

body for conception and pregnancy, and (2) the

two major phases: (1) preparation of the female

Female reproductive functions can be divided into

Pregnancy and Female Hormones

Female Physiology Before

1011

and Chapter 82 presents the physiology of preg-

Physiologic Anatomy of the Female

and vagina.

germinal epithe-

lium,

differentiate from this germinal epithe-

around it a layer of spindle cells from the ovarian stroma (the supporting tissue of

called
called a

is called a

atretic

capability (at menopause

gonadotropin-releasing hormone

(GnRH)

follicle-stimulating hormone (FSH)

and luteinizing hormone (LH), both of which are secreted in response to
the release of GnRH from the hypothalamus

estrogen and

which are secreted by

the ovaries in response to the two female sex hormones from the anterior
pituitary gland

menarche.

strual cycle is called

puberty,

between the ages of 11 and 15 years. This period of

to onset of normal monthly sexual cycles beginning

secrete progressively more FSH and LH, which leads

secreted. At age 9 to 12 years, the pituitary begins to

inactive, which is the case throughout childhood,

In the absence of these hormones, the ovaries remain

The ovarian changes that occur during the sexual cycle

single fetus will begin to grow at a time. Second, the

from the ovaries each month, so that normally only a

cycle. First, only a

There are two significant results of the female sexual

associated with decreased fertility.

women, although abnormal cycle length is frequently

may be as short as 20 days or as long as 45 days in some

). The duration of the cycle averages 28 days. It

(or, less accurately, the

organs. This rhythmical pattern is called the

The normal reproductive years of the female are char-

Hormones

Function of the Gonadotropic

the male.

pulses averaging once every 90 minutes, as occurs in

during the monthly sexual cycle. It is secreted in short

1012

Unit XIV

Endocrinology and Reproduction

Monthly Ovarian Cycle;

acterized by monthly rhythmical changes in the rates
of secretion of the female hormones and correspon-
ding physical changes in the ovaries and other sexual

female

monthly sexual cycle

menstrual

cycle

single ovum is normally released

uterine endometrium is prepared in advance for
implantation of the fertilized ovum at the required
time of the month.

Gonadotropic Hormones and
Their Effects on the Ovaries

depend completely on the gonadotropic hormones
FSH and LH, secreted by the anterior pituitary gland.

when almost no pituitary gonadotropic hormones are

change is called

and the time of the first men-

Both FSH and LH are

small glycoproteins having molecular weights of about
30,000.

Cervix

Entrance to

uterine tube

Uterine tube

Uterine cavity

Uterine tube (sectioned)

Vagina

Uterine tube

Fimbriae

Uterus

Ovary

Uterus

Urethra

Clitoris

Labium

minora

Labium

majora

Vagina

Cervix

Urinary

bladder

Ovary

Rectum

Anus

Female reproductive organs.

Figure 81–1

Ovarian ligament

Ovarian stroma

Perimetrium

Isthmus of uterine tube

Fimbriae

Ovarian vessels

Corpus albicans

Corpus luteum

Ovarian follicles

Broad ligament of uterus

Ampulla of
uterine tube

Mucosal folds
of uterine tube

Endometrium

Uterine cavity

Myometrium

Uterosacral

ligament

Cervical canal

Cervix

Vagina

Vaginal rugae

Isthmus of uterus

The amount of GnRH released from the hypothal-

Physiology of the Human Body,

(Redrawn from Guyton AC:

ovary, and a uterine tube.

Internal structures of the uterus,

Figure 81–2

6th ed. Philadelphia: Saunders
College Publishing, 1984.)

changing concentrations of the anterior pituitary
gonadotropic hormones FSH and LH (bottom two
curves) and of the ovarian hormones estradiol (estro-
gen) and progesterone (top two curves).

amus increases and decreases much less drastically

(discussed later). Accumulation of this fluid causes an

estrogen, one of the important female sex hormones

for a few days, the mass of granulosa cells secretes a

After the early proliferative phase of growth, lasting

the capsule of the developing follicle.

The outer layer, the

into two layers. In the

This is divided

several layers outside the granulosa cells, giving rise to

many more layers of these cells. In addition, spindle

rapid proliferation of the granulosa cells, giving rise to

to 12 primary follicles each month. The initial effect is

mones, especially FSH, cause accelerated growth of 6

that of LH and preceding it by a few days. These hor-

erately, with the increase in FSH slightly greater than

first few days of each monthly female sexual cycle,

Development of Antral and Vesicular Follicles.

primary follicles.

licles; these follicles are known as

diameter twofold to threefold. Then follows growth of

enlargement of the ovum itself, which increases in

The first stage of follicular growth is moderate

them, begin to grow.

ovaries, together with some of the follicles within

gland begin to be secreted in significant quantities, the

puberty, when FSH and LH from the anterior pituitary

the prophase stage of meiotic division. Then, after

Throughout childhood, the granulosa cells are

as shown in the figure.

primordial follicle,

losa cells; the ovum, with this granulosa cell sheath, is

growth in the ovaries. When a female child is born,

Figure 81–4 shows the progressive stages of follicular

Ovarian Follicle Growth—

that stimulate sex hormone synthesis, as explained in

cytoplasm, which causes the formation of

of the cells as well. Almost all these stimulatory

turn, the activated receptors increase the cells’ rates

receptors in the ovarian target cell membranes. In

which are explained in the following sections.

cyclical variations cause cyclical ovarian changes,

LH, as shown in the bottom of Figure 81–3. These

is a cyclical increase and decrease of both FSH and

During each month of the female sexual cycle, there

Female Physiology Before Pregnancy and Female Hormones

Chapter 81

1013

Both FSH and LH stimulate their ovarian target

cells by combining with highly specific FSH and LH

of secretion and usually the growth and proliferation

effects result from activation of the cyclic adenosine
monophosphate second messenger system in the cell

protein

kinase and multiple phosphorylations of key enzymes

Chapter 74.

“Follicular” Phase of the
Ovarian Cycle

each ovum is surrounded by a single layer of granu-

called a

believed to provide nourishment for the ovum and to
secrete an oocyte maturation-inhibiting factor that
keeps the ovum suspended in its primordial state in

additional layers of granulosa cells in some of the fol-

During the

the concentrations of both FSH and LH secreted by
the anterior pituitary gland increase slightly to mod-

cells derived from the ovary interstitium collect in

a second mass of cells called the theca.

theca interna, the cells take on

epithelioid characteristics similar to those of the gran-
ulosa cells and develop the ability to secrete additional
steroid sex hormones (estrogen and progesterone).

theca externa, develops into a

highly vascular connective tissue capsule that becomes

follicular fluid that contains a high concentration of

FSH and LH (ng/mL)

Estradiol (pg/mL)

0 2 4 6 8 10 12 14 16 18 20 22 24 26

FSH

Progesterone

800

600

Menstruation

Ovulation

Estradiol

Ovulation

400

200

600

400

200

Days of female sexual cycle

Progesterone (ng/mL)

follicle-stimulating hormone; LH, luteinizing hormone.

ovarian hormones during the normal female sexual cycle. FSH,

Approximate plasma concentrations of the gonadotropins and

Figure 81–3

Ovum

Antrum

Corona radiata

Corpus luteum

Ovulation

Degenerating

corpus luteum

Primordial

follicle

Preantral

follicle

Antral

follicle

Preovulatory

(mature) follicle

Zona pellucida

Theca

Granulosa cells

Corona radiata

Stages of follicular growth in the ovary, also showing formation of

Figure 81–4

the corpus luteum.

appearance.This process is called

They

lutein cells.

from the follicle, the remaining granulosa and theca

of the Ovarian Cycle

Phase

causes follicle rupture, with discharge of the ovum.

follicle swelling. Finally, the combination of follicle

transudation into the follicle, which contributes to

the follicular tissues. These two effects cause plasma

licle wall, and at the same time, prostaglandins (local

and degeneration of the stigma. (2) Simultaneously,

wall, resulting in further swelling of the entire follicle

from lysosomes, and these cause dissolution of the fol-

sary for ovulation: (1) The theca externa (the capsule

few hours, two events occur, both of which are neces-

steroid hormones that contain progesterone. Within a

gland. This LH causes rapid secretion of follicular

initiation of ovulation, showing the role of the large

Figure 81–5 gives a schema for the

ovulation will not take place.

occurs. Without the initial preovulatory surge of LH,

longed phase of excessive estrogen secretion, and (3)

follicle, (2) diminishing estrogen secretion after a pro-

fall about 1 day before ovulation, while increasing

fore, the rate of secretion of estrogen begins to

them mainly to progesterone-secreting cells. There-

effect on the granulosa and theca cells, converting

few days before ovulation. The LH also has a specific

the same time, and the FSH and LH act synergistically

ovulation. FSH also increases about 2-fold to 3-fold at

by the anterior pituitary gland increases markedly,

detail later in the chapter), the rate of secretion of LH

available, the follicle will not progress to the stage

hormone, even when large quantities of FSH are

for final follicular growth and ovulation. Without this

Surge of LH Is Necessary for Ovulation.

granulosa cells, called the

nate outward. This viscous fluid carries with it the

occupied the central portion of the follicle, to evagi-

widely, allowing a more viscous fluid, which has

stigma, and about 2 minutes later, the stigma ruptures

so, fluid begins to ooze from the follicle through the

protrudes like a nipple. In another 30 minutes or

in the center of the follicular capsule, called the

outer wall of the follicle swells rapidly, and a small area

menstruation. Shortly before ovulation, the protruding

female sexual cycle occurs 14 days after the onset of

mature follicle.

nancy. The single follicle reaches a diameter of 1 to 1.5

enough each month to ovulate; this usually prevents

This process of atresia is important, because it nor-

involute.

grow because of its intrinsic positive feedback effects,

follicles. Therefore, the largest follicle continues to

FSH secretion by the anterior pituitary gland, in this

postulated to be the following: The large amounts of

The cause of the atresia is unknown, but it has been

atretic.

begins to outgrow all the others; the remaining 5 to 11

Only One Follicle Fully Matures Each Month, and the Remain-

of granulosa cells located at one pole of the follicle.

enlarges, the ovum itself remains embedded in a mass

fold, or a mass increase of 1000-fold. As the follicle

fold, giving a total ovum diameter increase up to 10-

growth occurs almost explosively. The ovum itself

Once the antral follicles begin to grow, their

in follicular secretion. (3) The increasing estrogens

LH receptors on the original granulosa cells, thus

granulosa cells even more sensitive to FSH. (2) The

causes a positive feedback effect, because it makes the

to form increasing numbers of FSH receptors; this

ated growth is caused by the following: (1) Estrogen is

This acceler-

vesicular follicles.

Then greatly accelerated growth occurs, leading to still

the antral stage is stimulated mainly by FSH alone.

The early growth of the primary follicle up to

shown in Figure 81–4.

to appear within the mass of granulosa cells, as

1014

Unit XIV

Endocrinology and Reproduction

antrum

larger follicles called

secreted into the follicle and causes the granulosa cells

pituitary FSH and the estrogens combine to promote

allowing LH stimulation to occur in addition to FSH
stimulation and creating an even more rapid increase

from the follicle plus the increasing LH from the ante-
rior pituitary gland act together to cause proliferation
of the follicular thecal cells and increase their secre-
tion as well.

also enlarges in diameter another threefold to four-

der Undergo Atresia.

After a week or more of growth—

but before ovulation occurs—one of the follicles

developing follicles involute (a process called atresia),
and these follicles are said to become

estrogen from the most rapidly growing follicle act on
the hypothalamus to depress further enhancement of

way blocking further growth of the less well developed

while all the other follicles stop growing and actually

mally allows only one of the follicles to grow large

more than one child from developing with each preg-

centimeters at the time of ovulation and is called the

Ovulation

Ovulation in a woman who has a normal 28-day

stigma,

ovum surrounded by a mass of several thousand small

corona radiata.

LH is necessary

of ovulation.

About 2 days before ovulation (for reasons that are

not completely understood but are discussed in more

rising 6- to 10-fold and peaking about 16 hours before

to cause rapid swelling of the follicle during the last

amounts of progesterone begin to be secreted.

It is in this environment of (1) rapid growth of the

initiation of secretion of progesterone that ovulation

Initiation of Ovulation.

quantity of LH secreted by the anterior pituitary

of the follicle) begins to release proteolytic enzymes

licular capsular wall and consequent weakening of the

there is rapid growth of new blood vessels into the fol-

hormones that cause vasodilation) are secreted into

swelling and simultaneous degeneration of the stigma

Corpus Luteum—“Luteal”

During the first few hours after expulsion of the ovum

interna cells change rapidly into
enlarge in diameter two or more times and become
filled with lipid inclusions that give them a yellowish

luteinization, and the

follows.

and menstruation begins. A new ovarian cycle then

hormones estrogen and progesterone decrease greatly,

corpus luteum degenerates, whereupon the ovarian

progesterone and estrogen. After another 2 weeks, the

large quantities of both the major female hormones,

After ovulation, the secretory cells of the ovulating

14th day of the cycle. During growth of the follicles,

licles finally becomes “mature” and ovulates on the

cles to begin to grow in the ovaries. One of these fol-

About every 28 days, gonadotropic hormones from the

explained later.

this time also leads to menstruation by the uterus, as

of new follicles, beginning a new ovarian cycle. The

FSH and LH again. FSH and LH initiate the growth

terone, and inhibin by the corpus luteum removes the

sudden cessation of secretion of estrogen, proges-

2 days before menstruation begins. At this time, the

around the 26th day of the normal female sexual cycle,

almost exactly 12 days of corpus luteum life, which is

Final involution normally occurs at the end of

causes the corpus luteum to degenerate completely, a

FSH and LH result, and loss of these hormones finally

cially FSH secretion. Low blood concentrations of both

inhibits secretion by the anterior pituitary gland, espe-

by the Sertoli cells of the male testes. This hormone

In addition, the lutein cells secrete small amounts of

luteal phase of the ovarian cycle, have strong feedback

lesser extent, secreted by the corpus luteum during the

pregnancy.

which is secreted by the placenta, can

chorionic

pregnancy in Chapter 82 that another hormone with

in about 12 days. We shall see in the discussion of

secretion, followed by (4) degeneration. All this occurs

sequence of (1) proliferation, (2) enlargement, and (3)

to cause luteinization, the newly formed lutein cells

The corpus luteum is a highly secretory organ, secret-

tion-inhibiting factor,

local hormone in the follicular fluid, called

of the ovum from the follicle. A yet uncharacterized

“yellowing.” Luteinization also depends on extrusion

this function gives LH its name—“luteinizing,” for

on LH secreted by the anterior pituitary gland. In fact,

The change of granulosa and

during the ensuing few weeks, this is replaced

about 12 days after ovulation, becoming the

function as well as its yellowish, lipid characteristic

of development 7 to 8 days after ovulation. Then it

about 1.5 centimeters in diameter, reaching this stage

In the normal female, the corpus luteum grows to

hormones.

sex hormones. However, most of these hormones are

estrogen). The theca cells form mainly the androgens

The granulosa cells in the corpus luteum develop

which is shown in Figure 81–4. A well-developed

Female Physiology Before Pregnancy and Female Hormones

Chapter 81

1015

total mass of cells together is called the corpus luteum,

vascular supply also grows into the corpus luteum.

extensive intracellular smooth endoplasmic reticula
that form large amounts of the female sex hormones
progesterone and estrogen (more progesterone than

androstenedione and testosterone rather than female

also converted by the granulosa cells into the female

begins to involute and eventually loses its secretory

corpus

albicans;
by connective tissue and over months is absorbed.

Luteinizing Function of LH.

theca interna cells into lutein cells is dependent mainly

luteiniza-

seems to hold the luteinization

process in check until after ovulation.

Secretion by the Corpus Luteum: An Additional Function of LH.

ing large amounts of both progesterone and estrogen.
Once LH (mainly that secreted during the ovulatory
surge) has acted on the granulosa and theca cells

seem to be programmed to go through a preordained

almost exactly the same properties as LH,
gonadotropin,
act on the corpus luteum to prolong its life—usually
maintaining it for at least the first 2 to 4 months of

Involution of the Corpus Luteum and Onset of the Next Ovarian
Cycle.

Estrogen in particular and progesterone to a

effects on the anterior pituitary gland to maintain low
secretory rates of both FSH and LH.

the hormone inhibin, the same as the inhibin secreted

process called involution of the corpus luteum.

feedback inhibition of the anterior pituitary gland,
allowing it to begin secreting increasing amounts of

paucity of secretion of progesterone and estrogen at

Summary

anterior pituitary gland cause about 8 to 12 new folli-

mainly estrogen is secreted.

follicle develop into a corpus luteum that secretes

Weakened follicle wall

Luteinizing hormone

Follicle rupture

Evagination of ovum

Follicular steroid hormones

(progesterone)

Proteolytic enzymes

(collagenase)

Follicular hyperemia

and

prostaglandin secretion

Degeneration

of stigma

Plasma transudation

into follicle

Follicle swelling

Figure 81–5

Postulated mechanism of ovulation.

fates, and about one fifth of these conjugated products

The liver

period of 30 minutes or so.

esterone-binding globulins. The binding between these

Estrogens and Progesterone Are Transported in the Blood Bound

the plasma of the male by the testes.

into the circulating blood at this time. Also, about one

cells. During the luteal phase of the cycle, far too much

these two initial hormones can leave the ovaries,

during the follicular phase of the ovarian cycle, before

sex hormone testosterone are synthesized first; then,

During synthesis, mainly progesterone and the male

combine to form the appropriate steroid nucleus.

acetyl coenzyme A, multiple molecules of which can

in Figure 81–6 that they are all steroids. They are

pregnancy, especially after the fourth month of

As we shall see in Chapter 82, large amounts of

half of each ovarian cycle, when it is secreted by the

In the normal nonpregnant female, progesterone is

effects. Yet, for practical purposes, it is usually reason-

-hydroxyprogesterone, are secreted

progestin, 17-

is progesterone. However, small amounts of another

the estrogenic effects of estrone are not negligible.

estradiol is considered the major estrogen, although

that of the other two together. For this reason,

ing these relative potencies, one can see that the total

that of estrone and 80 times that of estriol. Consider-

The estrogenic potency of

occurring mainly in the liver.

from both estradiol and estrone, with the conversion

a weak estrogen; it is an oxidative product derived

adrenal cortices and by ovarian thecal cells. Estriol is

are also secreted, but most of this is formed in the

-estradiol. Small amounts of estrone

in Figure 81–6. The principal estrogen secreted by

estrone,

placenta, as discussed in Chapter 82.

pregnancy,

the adrenal cortices. During

ovaries, although minute amounts are also secreted by

female, estro-

prepare the uterus for pregnancy and the breasts for

of the female. The progestins function mainly to

The estro-

progesterone.

progestins.

The two types of ovarian sex hormones are the

and Progesterone

Hormones—Estradiol

1016

Unit XIV

Endocrinology and Reproduction

Functions of the Ovarian

estro-

gens and the

By far the most important of

the estrogens is the hormone estradiol, and by far the
most important progestin is
gens mainly promote proliferation and growth of spe-
cific cells in the body that are responsible for the
development of most secondary sexual characteristics

lactation.

Chemistry of the Sex Hormones

Estrogens.

In the normal nonpregnant

gens are secreted in significant quantities only by the

tremendous

quantities of estrogens are also secreted by the

Only three estrogens are present in significant quan-

tities in the plasma of the human female:

b-estradiol,

and estriol, the formulas for which are shown

the ovaries is

peripheral tissues from androgens secreted by the

b-estradiol is 12 times

estrogenic effect of

b-estradiol is usually many times

Progestins.

By far the most important of the progestins

along with progesterone and have essentially the same

able to consider progesterone the only important
progestin.

secreted in significant amounts only during the latter

corpus luteum.

progesterone are also secreted by the placenta during

gestation.

Synthesis of the Estrogens and Progestins.

Note from the

chemical formulas of the estrogens and progesterone

synthesized in the ovaries mainly from cholesterol
derived from the blood but also to a slight extent from

almost all the testosterone and much of the proges-
terone are converted into estrogens by the granulosa

progesterone is formed for all of it to be converted,
which accounts for the large secretion of progesterone

fifteenth as much testosterone is secreted into the
plasma of the female by the ovaries as is secreted into

to Plasma Proteins.

Both estrogens and progesterone

are transported in the blood bound mainly with
plasma albumin and with specific estrogen- and prog-

hormones and the plasma proteins is loose enough
that they are rapidly released to the tissues over a

Functions of the Liver in Estrogen Degradation.

conjugates the estrogens to form glucuronides and sul-

-Estradiol

Estrone

Progesterone

Estriol

Chemical formulas of the principal female hormones.

Figure 81–6

estrogens are administered. This mainly results from

a slight increase in total body protein, which is evi-

prevent the osteoporotic effects.

vertebrae, a large share of postmenopausal women are

and lead to bone fracture, especially fracture of the

Chapter 79. Because this can greatly weaken the bones

osteoporosis,

In some women, this effect is extremely severe, and the

decreased deposition of bone calcium and phosphate.

the bones, (2) decreased bone matrix, and (3)

deficiency leads to (1) increased osteoclastic activity in

estrogens are secreted by the ovaries. This estrogen

After menopause, almost no

ciency in Old Age.

normal time.

several years earlier than growth of the male. A female

male. As a result, growth of the female usually ceases

bones. This effect of estrogen in the female is much

another potent effect on skeletal growth: They cause

rapid for several years. However, estrogens have

her reproductive years, her growth in height becomes

late bone growth. At puberty, when the female enters

Effect of Estrogens on the Skeleton.

the breasts into milk-producing organs.

However, they do not complete the job of converting

breasts and of the milk-producing apparatus. They

In summary, the estrogens initiate growth of the

determinative growth and function of these structures.

extent under the influence of estrogens alone, but it

system, and (3) deposition of fat in the breasts. The

tissues of the breasts, (2) growth of an extensive ductile

the influence of appropriate hormones, the masculine

of females and males are exactly alike. In fact, under

The primordial breasts

Effect of Estrogens on the Breasts.

These cilia always beat toward the uterus, which helps

Also, activity of the cilia is considerably enhanced.

epithelial cells that line the fallopian tubes to increase.

especially important, they cause the number of ciliated

similar to that on the uterine endometrium.They cause

The estrogens’

Effect of Estrogens on the Fallopian Tubes.

cycle.

the implanted ovum. These effects are discussed later

glands, which will later aid in providing nutrition to

under the influence of estrogens. Estrogens cause

the uterus increases twofold to threefold, but more

During the first few years after puberty, the size of

is the prepubertal cuboidal cell epithelium. Vaginal

from a cuboidal into a stratified type, which is consid-

In addition, estrogens change the vaginal epithelium

times in size. Also, the external genitalia enlarge, with

lopian tubes, uterus, and vagina all increase several

those of a child to those of an adult. The ovaries, fal-

more. At this time, the female sex organs change from

in minute quantities, but at puberty, the quantity

During childhood, estrogens are secreted only

Functions of the Estrogens

fore, one can estimate the rate of progesterone

esterone is excreted in the urine in this form. There-

The major end product of progesterone degradation

estrogens, the liver is especially important for this

steroids that have no progestational effect. As with the

tion, almost all the progesterone is degraded to other

Within a few minutes after secre-

activity of estrogens in the body, sometimes causing

totally impotent estrogen estriol. Therefore, dimin-

excreted in the urine. Also, the liver converts the

is excreted in the bile; most of the remainder is

Female Physiology Before Pregnancy and Female Hormones

Chapter 81

1017

potent estrogens estradiol and estrone into the almost

ished liver function actually increases

the

hyperestrinism.

Fate of Progesterone.

metabolic degradation.

is pregnanediol. About 10 per cent of the original prog-

formation in the body from the rate of this excretion.

—

Their Effects on the Primary and
Secondary Female Sex Characteristics

A primary function of the estrogens is to cause cellu-
lar proliferation and growth of the tissues of the sex
organs and other tissues related to reproduction.

Effect of Estrogens on the Uterus and External Female Sex
Organs.

secreted in the female under the influence of the
pituitary gonadotropic hormones increases 20-fold or

deposition of fat in the mons pubis and labia majora
and enlargement of the labia minora.

erably more resistant to trauma and infection than

infections in children can often be cured by the admin-
istration of estrogens simply because of the resulting
increased resistance of the vaginal epithelium.

important than the increase in uterus size are the
changes that take place in the uterine endometrium

marked proliferation of the endometrial stroma
and greatly increased development of the endometrial

in the chapter in connection with the endometrial

effect on the mucosal lining of the fallopian tubes is

the glandular tissues of this lining to proliferate;

propel the fertilized ovum in that direction.

breast during the first 2 decades of life can develop
sufficiently to produce milk in the same manner as the
female breast.

Estrogens cause (1) development of the stromal

lobules and alveoli of the breast develop to a slight

is progesterone and prolactin that cause the ultimate

are also responsible for the characteristic growth
and external appearance of the mature female breast.

Estrogens inhibit

osteoclastic activity in the bones and therefore stimu-

uniting of the epiphyses with the shafts of the long

stronger than the similar effect of testosterone in the

eunuch who is devoid of estrogen production usually
grows several inches taller than a normal mature
female because her epiphyses do not unite at the

Osteoporosis of the Bones Caused by Estrogen
Defi

resulting condition is

described in

treated prophylactically with estrogen replacement to

Effect of Estrogens on Protein Deposition.

Estrogens cause

denced by a slight positive nitrogen balance when

the growth-promoting effect of estrogen on the sexual

cycle, the stromal cells and the epithelial cells

estrogens,

only a thin layer of endometrial stroma remains, and

desquamated by menstruation. After menstruation,

monthly cycle, most of the endometrium has been

cycle are shown in Figure 81–7.

The various phases of this endometrial

mation of the endometrium, which is known as

tory changes in the endometrium; and (3) desqua-

the uterine endometrium; (2) development of secre-

ates through the following stages: (1) proliferation of

endometrial cycle in the lining of the uterus that oper-

Associated with the monthly cyclical production

increased fluid in the subcutaneous tissue.

the lobules and alveoli, but part also results from

Progesterone also causes the breasts to swell. Part

milk; as discussed in Chapter 82, milk is secreted only

enlarge, and become secretory in nature. However,

the breasts, causing the alveolar cells to proliferate,

Effect of Progesterone on the Breasts.

necessary for nutrition of the fertilized, dividing ovum

lining of the fallopian tubes. These secretions are

Effect of Progesterone on the Fallopian Tubes.

of uterine contractions, thereby helping to prevent

progesterone decreases the frequency and intensity

with the endometrial cycle of the uterus.

ovum. This function is discussed later in connection

the latter half of the monthly female sexual cycle, thus

secretory changes in the uterine endometrium

Functions of Progesterone

body fluid retention, as discussed in Chapter 82.

nificance, but during pregnancy, the tremendous for-

sodium and water retention by the kidney tubules. This

terone and some other adrenocortical hormones, cause

hormones has been pointed out. Estrogens, like aldos-

The chemical

the skin to become more vascular; this is often associ-

of a child or a castrated female. Also, estrogens cause

but even so, the skin of a woman is thicker than that

responsible for this.

puberty. Androgens formed in increased quantities by

greatly affect hair distribution. However, hair does

characteristic of the feminine figure.

deposition of fat in the buttocks and thighs, which is

breasts and subcutaneous tissues, estrogens cause the

more protein. In addition to deposition of fat in the

greater than that in the male body, which contains

fat in the subcutaneous tissues. As a result, the per-

They also cause deposition of increased quantities of

increase caused by the male sex hormone testosterone.

slightly, but only about one third as much as the

erful as that caused by estrogens.

The enhanced protein deposition caused by testos-

organs, the bones, and a few other tissues of the body.

1018

Unit XIV

Endocrinology and Reproduction

terone is much more general and many times as pow-

Effect of Estrogens on Body Metabolism and Fat Deposition.

Estrogens increase the whole-body metabolic rate

centage of body fat in the female body is considerably

Effect of Estrogens on Hair Distribution.

Estrogens do not

develop in the pubic region and in the axillae after

the female adrenal glands after puberty are mainly

Effect of Estrogens on the Skin.

Estrogens cause the skin

to develop a texture that is soft and usually smooth,

ated with increased warmth of the skin and also pro-
motes greater bleeding of cut surfaces than is observed
in men.

Effect of Estrogens on Electrolyte Balance.

similarity of estrogenic hormones to adrenocortical

effect of estrogens is normally slight and rarely of sig-

mation of estrogens by the placenta may contribute to

Effect of Progesterone on the Uterus.

By far the most

important function of progesterone is to promote

during

preparing the uterus for implantation of the fertilized

In addition to this effect on the endometrium,

expulsion of the implanted ovum.

Progesterone

also promotes increased secretion by the mucosal

as it traverses the fallopian tube before implantation.

Progesterone

promotes development of the lobules and alveoli of

progesterone does not cause the alveoli to secrete

after the prepared breast is further stimulated by pro-
lactin from the anterior pituitary gland.

of this swelling is due to the secretory development in

Monthly Endometrial Cycle
and Menstruation

of estrogens and progesterone by the ovaries is an

menstruation.

Proliferative Phase (Estrogen Phase) of the Endometrial Cycle,
Occurring Before Ovulation.

At the beginning of each

the only epithelial cells that are left are those located
in the remaining deeper portions of the glands and
crypts of the endometrium. Under the influence of

secreted in increasing quantities by the

ovary during the first part of the monthly ovarian

(11 days)

Endometrial

thickness

Proliferative

phase

Secretory

phase

(12 days)

Menstrual

phase

(5 days)

Phases of endometrial growth and menstruation during each

Figure 81–7

monthly female sexual cycle.

mechanism that causes the cyclical variations.

cycle, we can attempt to explain the basic rhythmical

Now that we have presented the major cyclical

Hormones

Hypothalamic-Pituitary

denuded. This is of extreme protective value.

struation, even though the endometrial surfaces are

of these leukocytes and possibly other factors, the

necrosis causes this outflow of leukocytes. As a result

along with the necrotic material and blood. It is prob-

tion, tremendous numbers of leukocytes are released

of blood ceases because, by this time, the endometrium

Within 4 to 7 days after menstruation starts, the loss

clinical evidence of uterine pathology.

ting. The presence of clots during menstruation is often

bleeding occurs from the uterine surface, the quantity

with the necrotic endometrial material. If excessive

serous fluid are lost. The menstrual fluid is normally

During normal menstruation, approximately 40

uterine contents.

together, initiate uterine contractions that expel the

substances in the decaying desquamate, all acting

desquamated tissue and blood in the uterine cavity,

the endometrium have desquamated. The mass of

onset of menstruation, all the superficial layers of

of the hemorrhages until, about 48 hours after the

hours. Gradually, the necrotic outer layers of the

vascular layer of the endometrium, and the hemor-

blood vessels. As a result, blood at first seeps into the

initiate necrosis in the endometrium, especially of the

endometrium, and the loss of hormonal stimulation

The vasospasm, the decrease in nutrients to the

time.

effect of involution, such as release of a vasoconstric-

become vasospastic, presumably because of some

onset of menstruation, the tortuous blood vessels

thickness. Then, during the 24 hours preceding the

two hormones, followed rapidly by involution of the

end of the monthly ovarian cycle. The first effect is

gens and progesterone, especially progesterone, at the

Menstruation follows.

low levels of secretion, as shown in Figure 81–3.

in the ovary suddenly involutes, and the ovarian

before the end of the monthly cycle, the corpus luteum

If the ovum is not fertilized, about 2 days

nutrients available to the early implanting embryo.

stored substances, thus making great quantities of

the implanting ovum (in the blastocyst stage) begin to

endometrium, the trophoblastic cells on the surface of

dividing ovum. Then, once the ovum implants in the

called “uterine milk,” provide nutrition for the early

to 9 days after ovulation), the uterine secretions,

ovum during the latter half of the monthly cycle. From

fertilized

The whole purpose of all these endometrial changes

6 millimeters.

ovulation, the endometrium has a thickness of 5 to

the peak of the secretory phase, about 1 week after

with the blood vessels becoming highly tortuous. At

in proportion to the developing secretory activity,

deposits increase greatly in the stromal cells; and the

plasm of the stromal cells increases; lipid and glycogen

mulates in the glandular epithelial cells. Also, the cyto-

in tortuosity; an excess of secretory substances accu-

development of the endometrium. The glands increase

endometrium during this phase of the cycle, whereas

large quantities by the corpus luteum. The estrogens

half of the monthly cycle, after ovulation has occurred,

Secretory Phase (Progestational Phase) of the Endometrial

uterus.

the cervical canal, forming channels that help guide

vical region, secrete a thin, stringy mucus. The mucus

The endometrial glands, especially those of the cer-

metrium. At the time of ovulation, the endometrium is

greatly in thickness, owing to increasing numbers of

Then, during the next week and a half—that is,

proliferate rapidly. The endometrial surface is re-

Female Physiology Before Pregnancy and Female Hormones

Chapter 81

1019

epithelialized within 4 to 7 days after the beginning of
menstruation.

before ovulation occurs—the endometrium increases

stromal cells and to progressive growth of the endome-
trial glands and new blood vessels into the endo-

3 to 5 millimeters thick.

strings actually align themselves along the length of

sperm in the proper direction from the vagina into the

Cycle, Occurring After Ovulation.

During most of the latter

progesterone and estrogen together are secreted in

cause slight additional cellular proliferation in the

progesterone causes marked swelling and secretory

blood supply to the endometrium further increases

is to produce a highly secretory endometrium that con-
tains large amounts of stored nutrients to provide
appropriate conditions for implantation of a

the time a fertilized ovum enters the uterine cavity
from the fallopian tube (which occurs 3 to 4 days
after ovulation) until the time the ovum implants (7

digest the endometrium and absorb the endometrial

Menstruation.

hormones (estrogens and progesterone) decrease to

Menstruation is caused by the reduction of estro-

decreased stimulation of the endometrial cells by these

endometrium itself to about 65 per cent of its previous

leading to the mucosal layers of the endometrium

tor material—possibly one of the vasoconstrictor types
of prostaglandins that are present in abundance at this

rhagic areas grow rapidly over a period of 24 to 36

endometrium separate from the uterus at the sites

plus contractile effects of prostaglandins or other

milliliters of blood and an additional 35 milliliters of

nonclotting because a fibrinolysin is released along

of fibrinolysin may not be sufficient to prevent clot-

has become re-epithelialized.

Leukorrhea During Menstruation.

During menstrua-

able that some substance liberated by the endometrial

uterus is highly resistant to infection during men-

Regulation of the Female
Monthly Rhythm—Interplay
Between the Ovarian and

changes that occur during the monthly female sexual

LH at the end of the monthly female sexual cycle.

extent, LH by the anterior pituitary gland. Therefore,

male—inhibiting the secretion of FSH and, to a lesser

Sertoli cells secrete inhibin in the male testes. This

involved, especially

gen and progesterone, other hormones seem to be

frequency of the GnRH pulses.

decrease secretion of GnRH, especially by altering the

the anterior pituitary gland directly, but they also

These feedback effects seem to operate mainly on

estrogen is multiplied, even though progesterone by

when progesterone is available, the inhibitory effect of

inhibit the production of both LH and FSH. Also,

and FSH Secretion

and Progesterone in Decreasing Both LH

Negative Feedback Effects of Estrogen

release and the frequency of the pulses, thus providing

ronal centers in the higher brain’s “limbic” system (the

secrete GnRH in moderate amounts. Multiple neu-

female sexual activity, although neurons located in the

in the arcuate nuclei of this area. Therefore, it is

primarily in the mediobasal hypothalamus, especially

The neuronal

This is shown by the upper curve in Figure 81–8.

tent output of LH secretion about every 90 minutes.

The pulsatile release of GnRH also causes intermit-

reasons unknown, the pulsatile nature of GnRH

by the anterior pituitary gland is lost. Therefore, for

pulses, its ability to cause the release of LH and FSH

occur every 1 to 2 hours. The lower curve in Figure

Stimulates Pulsatile Release of LH from the Anterior Pituitary

Glu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH

is important. This hormone has been purified

case of the gonadotropins, one releasing hormone,

the hypothalamic-hypophysial portal system. In the

hormones” formed in the hypothalamus and then

anterior pituitary hormones is controlled by “releasing

As pointed out in Chapter 74, secretion of most of the

Causes the Anterior Pituitary Gland to Secrete

The Hypothalamus Secretes GnRH, Which

1020

Unit XIV

Endocrinology and Reproduction

LH and FSH

transported to the anterior pituitary gland by way of

GnRH,
and has been found to be a decapeptide with the
following formula:

Intermittent, Pulsatile Secretion of GnRH by the Hypothalamus

Gland.

Experiments have demonstrated that the hypo-

thalamus does not secrete GnRH continuously but
instead secretes it in pulses lasting 5 to 25 minutes that

81–8 shows the electrical pulsatile signals in the hypo-
thalamus that cause the hypothalamic pulsatile output
of GnRH.

It is intriguing that when GnRH is infused continu-

ously so that it is available all the time rather than in

release is essential to its function.

Hypothalamic Centers for Release of GnRH.

activity that causes pulsatile release of GnRH occurs

believed that these arcuate nuclei control most

preoptic area of the anterior hypothalamus also

system for psychic control) transmit signals into the
arcuate nuclei to modify both the intensity of GnRH

a partial explanation of why psychic factors often
modify female sexual function.

Estrogen in small amounts has a strong effect to

itself has little effect.

operate to a lesser extent on the hypothalamus to

Hormone Inhibin from the Corpus Luteum Inhibits FSH and LH
Secretion.

In addition to the feedback effects of estro-

inhibin, which is secreted along

with the steroid sex hormones by the granulosa cells
of the ovarian corpus luteum in the same way that

hormone has the same effect in the female as in the

it is believed that inhibin might be especially impor-
tant in causing the decrease in secretion of FSH and

120

240

360

480

MUA

1000

2000

100

Minutes

Multi-unit electrical activity (MUA)

(spikes/min)

Luteinizing hormone (LH)

(ng/mL)

hormone secretion. Neuroen-

correlates of pulsatile luteinizing

al: Central electrophysiologic

hypothalamus. (Data from Wilson

recording of multi-unit electrical

ovariectomized rhesus monkey.

peripheral circulation of a

luteinizing hormone (LH) in the

Figure 81–8

Upper curve: Pulsatile change in

p e n t o b a r b i t a l - a n e s t h e t i z e d

Lower curve: Minute-by-minute

activity (MUA) in the mediobasal

RC, Kesner JS, Kaufman JM, et

docrinology 39:256, 1984.)

means the beginning of the cycle of

menarche

means the onset of adult sexual life, and

months to years before menopause, presumably

usually anovulatory, as are the cycles occurring several

The first few cycles after the onset of puberty are

itself, although it can alter its rhythm.

terone is not required for maintenance of the cycle

rhythm continues. Therefore, it is likely that proges-

Second, the cycle is shortened by several days, but the

of progesterone during the latter portion of the cycle.

of the corpus luteum, so there is almost no secretion

First, lack of ovulation causes failure of development

continue, but they are altered in the following ways:

said to be “anovulatory.” The phases of the sexual cycle

magnitude, ovulation will not occur, and the cycle is

Anovulatory Cycles—Sexual Cycles at Puberty

luteum. Thus, the hormonal system begins its new

ever the cause of this preovulatory LH and FSH surge,

the secretion of LH and, to a lesser extent, FSH. What-

as explained earlier, which leads to a terrific surge in

feedback stimulatory effect on the anterior pituitary,

to an abrupt halt. It is believed that the high level of

cycle, the decline in secretion of FSH and LH comes

3. Preovulatory Surge of LH and FSH Causes Ovulation.

FSH. This is the preovulatory surge of LH and FSH,

increase in the secretion of LH and, to a lesser extent,

pituitary gland. Then there is a sudden, marked

feedback effect, mainly of estrogen, on the anterior

new female monthly sexual cycle.

in the secretion of estrogen, reaching a peak estrogen

tion increases slightly as well. These hormones initiate

then, several days after menstruation begins, LH secre-

of FSH begins to increase again, as much as twofold;

the time that menstruation begins, pituitary secretion

these hormones. Therefore, a day or so later, at about

to a low ebb. This releases the hypothalamus and

terone, and inhibin from the corpus luteum decreases

total involution, and the secretion of estrogen, proges-

struation, the corpus luteum has regressed to almost

Two to 3 days before men-

tion. These effects are shown in Figure 81–3.

hypothalamus, causing the suppression of both FSH

esterone and estrogen, as well as the hormone inhibin.

the beginning of menstruation. During this time, the

of the cycle to explain is the events that occur during

The easiest part

Depression of the Pituitary Gonadotropins.

1. Postovulatory Secretion of the Ovarian Hormones, and

events.

rhythm of the female sexual cycle. It seems to operate

of the female hormonal system, we can attempt to

Now, after discussing much of the known information

Feedback Oscillation of the

ovulation will not occur.

Without this normal preovulatory surge of LH,

latory LH surge, and it has been suggested that this

of the female monthly cycle. (2) The granulosa cells of

extent, FSH; this is in sharp contrast to its normal neg-

of stimulating pituitary secretion of LH and, to a lesser

positive feedback effect

point in the cycle has a peculiar

follows: (1) It has been suggested that estrogen at this

known. However, several possible explanations are as

The cause of this abrupt surge in LH secretion is not

tion of LH causes ovulation to occur.

increases about twofold. The greatly increased secre-

abruptly sixfold to eightfold, and secretion of FSH

slightly suppressed. Then secretion of LH increases

estrogens. During this period, secretions of both FSH

cles, as well as rapidly accelerating secretion of ovarian

the latter part of the first half of the ovarian cycle will

The figure shows a much smaller preovulatory surge

ovulation. This effect is demonstrated in Figure 81–3.

For reasons not completely understood, the anterior

Ovulation—The Preovulatory LH Surge

Positive Feedback Effect of Estrogen Before

Female Physiology Before Pregnancy and Female Hormones

Chapter 81

1021

pituitary gland secretes greatly increased amounts of
LH for 1 to 2 days beginning 24 to 48 hours before

of FSH as well.

Experiments have shown that infusion of estrogen

into a female above a critical rate for 2 to 3 days during

cause rapidly accelerating growth of the ovarian folli-

and LH by the anterior pituitary gland are at first

ative feedback effect that occurs during the remainder

the follicles begin to secrete small but increasing quan-
tities of progesterone a day or so before the preovu-

might be the factor that stimulates the excess LH
secretion.

Hypothalamic-Pituitary-Ovarian
System

about the interrelations of the different components

explain the feedback oscillation that controls the

in approximately the following sequence of three

the postovulatory phase—between ovulation and

corpus luteum secretes large quantities of both prog-

All these hormones together have a combined nega-
tive feedback effect on the anterior pituitary gland and

and LH secretion and decreasing them to their lowest
levels about 3 to 4 days before the onset of menstrua-

2. Follicular Growth Phase.

anterior pituitary from the negative feedback effect of

new ovarian follicle growth and a progressive increase

secretion at about 12.5 to 13 days after the onset of the

During the first 11 to 12 days of this follicle growth,

the rates of pituitary secretion of the gonadotropins
FSH and LH decrease slightly because of the negative

which is followed by ovulation.

about 11.5 to 12 days after the onset of the monthly

estrogens at this time (or the beginning of proges-
terone secretion by the follicles) causes a positive

the great excess of LH leads to both ovulation and sub-
sequent development of and secretion by the corpus

round of secretions until the next ovulation.

If the preovulatory surge of LH is not of sufficient

because the LH surge is not potent enough at these
times to cause ovulation.

Puberty and Menarche

Puberty

menopausal women can likely avoid severe symptoms.

toms, and by gradually decreasing the dose, post-

treatment. If counseling fails, daily administration of

out the body. These symptoms are of sufficient magni-

(6) occasionally various psychotic states, and (7)

of dyspnea, (3) irritability, (4) fatigue, (5) anxiety,

by extreme flushing of the skin, (2) psychic sensations

of the body, including (1) “hot flushes” characterized

devoid of these hormones. The loss of estrogens often

At the time of menopause, a woman must readjust

the ovaries falls virtually to zero.

licles become atretic, the production of estrogens by

tinuous quantities, but as the remaining primordial fol-

Figure 81–9, the gonadotropins FSH and LH (mainly

gonadotropins FSH and LH. Instead, as shown in

production falls below a critical value, the estrogens

primordial follicles approaches zero. When estrogen

and, as shown in Figure 81–10, the production of

degenerate. At about age 45 years, only a few primor-

follicles and ovulate, and hundreds of thousands of ova

ovaries. Throughout a woman’s reproductive life,

The cause of menopause is “burning out” of the

menopause.

cycle ceases and the female sex hormones diminish to

shown in Figure 81–10. The period during which the

months to a few years, the cycle ceases altogether, as

irregular, and ovulation often fails to occur.After a few

At age 40 to 50 years, the sexual cycle usually becomes

secretion beyond menopause.

and, finally, (5) almost no estrogen or progesterone

estrogen secretion toward the end of reproductive life,

of reproductive life, (4) the progressive decrease in

during the monthly sexual cycle, (3) the further

gen secretion at puberty, (2) the cyclical variation

Figure 81–10 shows (1) the increasing levels of estro-

where in the brain, perhaps somewhere in the limbic

fore, it is now believed that the onset of puberty is

area of brain to cause the secretion is lacking. There-

hormone, but the appropriate signal from some other

during childhood. Experiments have shown that

male, and for reasons not understood, the hypothala-

priately stimulated. However, as is also true in the

In the female, as in the male, the infantile pituitary

11 and 16 years in girls (average, 13 years).

life, as shown in Figure 81–9, and usually culminating

by the pituitary, beginning in about the eighth year of

menstruation. The period of puberty is caused by a

1022

Unit XIV

Endocrinology and Reproduction

gradual increase in gonadotropic hormone secretion

in the onset of puberty and menstruation between ages

gland and ovaries are capable of full function if appro-

mus does not secrete significant quantities of GnRH

the hypothalamus itself is capable of secreting this

initiated by some maturation process that occurs else-

system.

increase in estrogen secretion during the first few years

Menopause

almost none is called

about 400 of the primordial follicles grow into mature

dial follicles remain to be stimulated by FSH and LH,

estrogens by the ovaries decreases as the number of

can no longer inhibit the production of the

FSH) are produced after menopause in large and con-

her life from one that has been physiologically stimu-
lated by estrogen and progesterone production to one

causes marked physiological changes in the function

decreased strength and calcification of bones through-

tude in about 15 per cent of women to warrant

estrogen in small quantities usually reverses the symp-

Female

Male

Puberty

Menopause

Age (yr)

Total urinary gonadotropins

(rat units/24 hr)

cially abrupt increase in gonadotropic hormones at menopause in

Total rates of secretion of gonadotropic hormones throughout the

Figure 81–9

sexual lives of female and male human beings, showing an espe-

the female.

400

300

100

Age (yr)

Estrogens excreted in urine

(

g/24 hr)

Puberty

Menopause

Estrogen secretion throughout the sexual life of the female human

Figure 81–10

being.

emission and ejaculation in the male, and it may help

The female orgasm is analogous to

initiated that cause the female orgasm, also called

conditioning signals from the cerebrum, reflexes are

maximum intensity, and especially when the local

When local sexual stimulation reaches

climaxes.

by a dry vagina. A massaging sensation constitutes

than an irritative sensation, which may be provoked

glands. This lubrication is necessary during intercourse

lubrication during sexual intercourse, although much

the introitus. This mucus is responsible for much of the

Bartholin’s glands located beneath the labia minora

stimulation for ejaculation to occur.

that the introitus tightens around the penis; this aids

polypeptide (VIP) at the nerve endings. This allows

of acetylcholine, nitric oxide, and vasoactive intestinal

of the erectile tissue, probably resulting from release

stimulation, parasympathetic signals dilate the arteries

the external genitalia. In the early phases of sexual

penis. This erectile tissue, like that of the penis, is

female sexual organs.

transmitted to the cerebrum. Also, local reflexes inte-

these signals have entered the spinal cord, they are

through the pudendal nerve and sacral plexus. Once

As in the male, the sexual sensory signals are trans-

tiating sexual sensations.

The glans of the

other perineal regions can create sexual sensations.

and other types of stimulation of the vulva, vagina, and

reaching a peak near the time of ovulation, probably

Desire also changes during the monthly sexual cycle,

ological drive, although sexual desire does increase in

woman’s background training as well as on her physi-

female sexual act. Such desire is based largely on a

desire, and this aids greatly in the performance of the

Thinking sexual thoughts can lead to female sexual

sexual act, successful performance of the female sexual

exists.

bleeding from this endometrium. In fact, bleeding is

which exert the usual estrogenic effects, including

These tumors secrete large quantities of estrogens,

occurring more often after menopause than before.

can develop in an ovary,

feminizing tumor develops.

hormones. Consequently, hypersecretion of feminizing

pituitary, and this limits the production of ovarian

ovarian hormones by the ovaries is a rare clinical entity,

of the preovulatory surge of LH, which is necessary for

frequently associated with failure of ovulation, presum-

altogether (amenorrhea). Prolonged ovarian cycles are

between menstrual periods, or menstruation may cease

not occur normally. Instead, several months may elapse

the ovarian cycle often does

small quantities of estrogens as a result of other factors,

order to cause rhythmical sexual cycles. Consequently,

cussion of menopause, the quantity of estrogens pro-

Irregularity of Menses, and Amenorrhea Caused by

menopause.

thinner. The same changes occur in women after

and become pendulous, and the pubic hair becomes

becomes thin and easily damaged. The breasts atrophy

vagina becomes smaller, and the vaginal epithelium

that the uterus becomes almost infantile in size, the

removed, the sexual organs regress to some extent so

When the ovaries of a fully developed woman are

early as they do in a normal woman. Consequently, the

organs remain infantile. Especially characteristic of

sexual characteristics do not appear, and the sexual

occurs. In this condition, the usual secondary

eunuchism

they become nonfunctional before puberty,

cells. When ovaries are absent from birth or when

can result from poorly formed ovaries, lack of ovaries,

Abnormalities of Secretion

Female Physiology Before Pregnancy and Female Hormones

Chapter 81

1023

by the Ovaries

Hypogonadism.

Less than normal secretion by the ovaries

or genetically abnormal ovaries that secrete the wrong
hormones because of missing enzymes in the secretory

female

this condition is prolonged growth of the long bones
because the epiphyses do not unite with the shafts as

female eunuch is essentially as tall as or perhaps even
slightly taller than her male counterpart of similar
genetic background.

Hypogonadism.

As pointed out in the preceding dis-

duced by the ovaries must rise above a critical value in

in hypogonadism or when the gonads are secreting

such as hypothyroidism,

ably because of insufficient secretion of LH at the time

ovulation.

Hypersecretion by the Ovaries.

Extreme hypersecretion of

because excessive secretion of estrogens automatically
decreases the production of gonadotropins by the

hormones is usually recognized clinically only when a

A rare granulosa cell tumor

hypertrophy of the uterine endometrium and irregular

often the first and only indication that such a tumor

Female Sexual Act

Stimulation of the Female Sexual Act.

As is true in the male

act depends on both psychic stimulation and local
sexual stimulation.

proportion to the level of sex hormones secreted.

because of the high levels of estrogen secretion during
the preovulatory period.

Local sexual stimulation in women occurs in more

or less the same manner as in men because massage

clitoris is especially sensitive for ini-

mitted to the sacral segments of the spinal cord

grated in the sacral and lumbar spinal cord are at least
partly responsible for some of the reactions in the

Female Erection and Lubrication.

Located around the

introitus and extending into the clitoris is erectile
tissue almost identical to the erectile tissue of the

controlled by the parasympathetic nerves that pass
through the nervi erigentes from the sacral plexus to

rapid accumulation of blood in the erectile tissue so

the male greatly in his attainment of sufficient sexual

Parasympathetic signals also pass to the bilateral

and cause them to secrete mucus immediately inside

is also provided by mucus secreted by the vaginal
epithelium and a small amount from the male urethral

to establish a satisfactory massaging sensation rather

the optimal stimulus for evoking the appropriate
reflexes that culminate in both the male and female

Female Orgasm.

sensations are supported by appropriate psychic

the female climax.

hyposecretion of gonadotropic hormones, in which

sterility is failure to ovulate. This can result from

the ova themselves.

organs, in which case it must be assumed that the infer-

10 per cent of women are infertile. Occasionally, no

Abnormal Conditions That Cause Female Sterility.

to occur and a new cycle to begin.

occur. Then the drug is stopped, allowing menstruation

begun in the early stages of the monthly cycle and con-

The drug is usually

odrel, ethynodiol,

norethindrone, norethyn-

Two of the most commonly used synthetic estrogens

destructive propensity of the liver, thus allowing oral

testinal tract into the portal circulation. However,

and synthetic progestins. The main reason for using syn-

Therefore, almost all “pills” used for the control of fer-

terone, especially the 19-norsteroids, along with small

cause abnormal menstrual bleeding patterns. However,

effects. For instance, too much of either hormone can

suppress ovulation but do not cause other, unwanted

The problem in devising methods for the hormonal

anterior pituitary that leads to the LH surge. The admin-

by the ovarian follicles, and this might be the necessary

gested that immediately before the surge occurs, there

fully understood. However, experimental work has sug-

Why the administration of estrogen or progesterone

surge of LH secretion by the pituitary gland, which is

The reason for this is that appropriate administration of

the first half of the monthly cycle, can inhibit ovulation.

progesterone, if given in appropriate quantities during

regular.

used only when the periodicity of the menstrual cycle is

conception. But such a method of contraception can be

the 7th day of the cycle. Therefore, it is usually stated

cycle is 21 days, ovulation usually occurs within 1 day of

the 26th day of the cycle. Finally, if the periodicity of the

cycle is 40 days, ovulation usually occurs within 1 day of

day of the cycle. If, in contrast, the periodicity of the

days, ovulation usually occurs within 1 day of the 14th

strual cycle is regular, with an exact periodicity of 28

always between 13 and 15 days. Therefore, if the men-

time of ovulation. Yet the interval from ovulation until

course near the time of ovulation. The difficulty with

days.

female fertility during each month is short, about 4 to 5

up to a few hours after ovulation. Thus, the period of

fore, for fertilization to take place, intercourse must

in the female reproductive tract for up to 5 days. There-

tilization is to take place. A few sperm can remain fertile

fore, sperm must be available soon after ovulation if fer-

from the ovary probably no longer than 24 hours. There-

The ovum remains

Female Fertility

terized by relaxed peacefulness, an effect called

culmination of the sexual act, this gives way during the

intense muscle tension throughout the body. But after

fertilization, the intense sexual sensations that develop

achieve. Whether this occurs in the human female is

of the fallopian tube in the cow in about 5 minutes, a

lated to cause increased transport of the sperm. A few

cal contractions of the uterus, which have been postu-

the pituitary. The oxytocin causes increased rhythmi-

the posterior pituitary gland to secrete oxytocin; this

Second, in many lower animals, copulation causes

minutes, thus allowing easy transport of the sperm.

subject is scanty, however. Also, the orgasm seems to

the uterus toward the ovum; information on this

the male. It is possible that these reflexes increase

female contract rhythmically, which results from spinal

First, during the orgasm, the perineal muscles of the

this are as follows.

function of the female orgasm. Possible reasons for

by artificial methods, thus indicating an important

promote fertilization of the ovum. Indeed, the human

1024

Unit XIV

Endocrinology and Reproduction

female is known to be somewhat more fertile when
inseminated by normal sexual intercourse rather than

cord reflexes similar to those that cause ejaculation in

uterine and fallopian tube motility during the orgasm,
thus helping to transport the sperm upward through

cause dilation of the cervical canal for up to 30

effect is probably mediated through the brain amyg-
daloid nuclei and then through the hypothalamus to

sperm have been shown to traverse the entire length

rate at least 10 times as fast as that which the swim-
ming motions of the sperm themselves could possibly

unknown.

In addition to the possible effects of the orgasm on

during the orgasm also pass to the cerebrum and cause

succeeding minutes to a sense of satisfaction charac-

resolution.

Fertile Period of Each Sexual Cycle.

viable and capable of being fertilized after it is expelled

occur sometime between 4 and 5 days before ovulation

Rhythm Method of Contraception.

One of the commonly

practiced methods of contraception is to avoid inter-

this method of contraception is predicting the exact

the next succeeding onset of menstruation is almost

that avoidance of intercourse for 4 days before the cal-
culated day of ovulation and 3 days afterward prevents

Hormonal Suppression of Fertility—“The Pill.”

It has long

been known that administration of either estrogen or

either of these hormones can prevent the preovulatory

essential in causing ovulation.

prevents the preovulatory surge of LH secretion is not

is probably a sudden depression of estrogen secretion

signal that causes the subsequent feedback effect on the

istration of sex hormones (estrogens or progesterone)
could prevent the initial ovarian hormonal depression
that might be the initiating signal for ovulation.

suppression of ovulation has been in developing appro-
priate combinations of estrogens and progestins that

use of certain synthetic progestins in place of proges-

amounts of estrogens usually prevents ovulation yet
allows an almost normal pattern of menstruation.

tility consist of some combination of synthetic estrogens

thetic estrogens and progestins is that the natural hor-
mones are almost entirely destroyed by the liver within
a short time after they are absorbed from the gastroin-

many of the synthetic hormones can resist this

administration.

are ethinyl estradiol and mestranol. Among the most
commonly used progestins are

and norgestrel.

tinued beyond the time that ovulation would normally

About 5 to

abnormality can be discovered in the female genital

tility is due to either abnormal physiological function of
the genital system or abnormal genetic development of

Probably by far the most common cause of female

case the intensity of the hormonal stimuli is simply

of female infertility. JAMA 290:1767, 2003.

Smith S, Pfeifer SM, Collins JA: Diagnosis and management

practice. N Engl J Med 348:618, 2003.

Riggs BL, Hartmann LC: Selective estrogen-receptor mod-

resorption. J Clin Invest 106:1203, 2000.

Riggs BL: The mechanisms of estrogen regulation of bone

in estrogen action. Annu Rev Physiol 63:165, 2001.

Pettersson K, Gustafsson JA: Role of estrogen receptor beta

tives. N Engl J Med 349:1443, 2003.

Petitti DB: Combination estrogen-progestin oral contracep-

Physiol Rev 80:1, 2000.

Niswender GD, Juengel JL, Silva PJ, et al: Mechanisms con-

gen action. Physiol Rev 81:1535, 2001.

Nilsson S, Makela S, Treuter E, et al: Mechanisms of estro-

291:1610, 2004.

gen for treatment of hot flashes: scientific review. JAMA

Nelson HD: Commonly used types of postmenopausal estro-

16:251, 2001.

membrane, cytosolic, and nuclear effects. News Physiol Sci

Nadal A, Diaz M, Valverde MA: The estrogen trinity:

replacement therapy. N Engl J Med 345:34, 2001.

Manson JE, Martin KA: Postmenopausal hormone-

regulate bone mass. J Clin Invest 111:1641, 2003.

Lorenzo J: A new hypothesis for how sex steroid hormones

Hamilton-Fairley D, Taylor A: Anovulation. BMJ 327:546,

duction and actions of estrogens. N Engl J Med 346:340,

Gruber CJ, Tschugguel W, Schneeberger C, Huber JC: Pro-

Compston JE: Sex steroids and bone. Physiol Rev 81:419,

therapy. Lancet 360:942, 2002.

Beral V, Banks E, Reeves G: Evidence from randomised

menopausal? JAMA 289:895, 2003.

Bastian LA, Smith CM, Nanda K: Is this woman peri-

porosis. JAMA 285:1415, 2001.

Altkorn D, Vokes T: Treatment of postmenopausal osteo-

low-grade infection or inflammation, or abnormal hor-

“threads.” Abnormalities of the cervix itself, such as

of ovulation, the hormonal environment of estrogen

mal mucus by the uterine cervix. Ordinarily, at the time

infertility.

of gonococcal infection, but with modern therapy,

the past, such inflammation occurred mainly as a result

causes fibrosis in the tubes, thereby occluding them. In

that is,

ingitis,

lopian tubes, either at the fimbriated ends or elsewhere

abdominal cavity. Often, endometriosis occludes the fal-

pelvis, and this fibrosis sometimes so enshrouds

ovaries. Endometriosis causes fibrosis throughout the

cavity surrounding the uterus, fallopian tubes, and

endometriosis,

with this hormone.

simultaneously; this results in multiple births, an effect

erful stimulator of ovulation. However, excess use of

This hormone, although secreted by the placenta, has

man chorionic gonadotropin,

illustrated in Figure 81–11.

temperature chart, showing the point of ovulation, is

rise coming abruptly at the time of ovulation. Such a

the body temperature about 0.5°F, with the temperature

progesterone during the latter half of the cycle raises

body temperature throughout the cycle. Secretion of

metabolism, during the latter half of the sexual cycle;

surge in pregnanediol, the end product of progesterone

effects, the cycle can be assumed to be anovulatory.

of anovulatory cycles. In the absence of progestational

body, because the normal increase in progesterone

determine whether ovulation occurs. These methods are

sterile women, special methods are often used to

outsides of the ovaries, making ovulation difficult.

instance, thick ovarian capsules occasionally exist on the

abnormal ovaries that do not allow ovulation. For

insufficient to cause ovulation, or it can result from

Female Physiology Before Pregnancy and Female Hormones

Chapter 81

1025

Because of the high incidence of anovulation in

based mainly on the effects of progesterone on the

secretion usually does not occur during the latter half

One of these tests is simply to analyze the urine for a

the lack of this substance indicates failure of ovulation.
Another common test is for the woman to chart her

Lack of ovulation caused by hyposecretion of the

pituitary gonadotropic hormones can sometimes be
treated by appropriately timed administration of hu-

a hormone (discussed in

Chapter 82) that is extracted from the human placenta.

almost the same effects as LH and is therefore a pow-

this hormone can cause ovulation from many follicles

that has caused as many as eight babies (mostly
stillborn) to be born to mothers treated for infertility

One of the most common causes of female sterility is

a common condition in which endome-

trial tissue almost identical to that of the normal uterine
endometrium grows and even menstruates in the pelvic

the ovaries that an ovum cannot be released into the

along their extent.

Another common cause of female infertility is salp-

inflammation of the fallopian tubes; this

this is becoming a less prevalent cause of female

Still another cause of infertility is secretion of abnor-

causes the secretion of mucus with special charac-
teristics that allow rapid mobility of sperm into the
uterus and actually guide the sperm up along mucous

monal stimulation of the cervix can lead to a viscous
mucous plug that prevents fertilization.

References

trials on the long-term effects of hormone replacement

2001.

2002.

2003.

trolling the function and life span of the corpus luteum.

ulators—mechanisms of action and application to clinical

0 2

4 6

8 10 12 14 16 18 20 22 24 26 28

Day of cycle

Body temperature (

Ovulation

Elevation in body temperature shortly after ovulation.

Figure 81–11

molecular specificity. Physiol Rev 82:923, 2002.

hormone receptor interactions: physiological flexibility by

Vasudevan N, Ogawa S, Pfaff D: Estrogen and thyroid

local regulation of the growth plate. Endocr Rev 24:782,

van der Eerden BC, Karperien M, Wit JM: Systemic and

the brain: where will it end? Endocrinology 145:1069,

Toran-Allerand CD: A plethora of estrogen receptors in

of the onset of puberty in primates. Endocr Rev 22:111,

Terasawa E, Fernandez DL: Neurobiological mechanisms

1026

Unit XIV

Endocrinology and Reproduction

2001.

2004.

2003.