Download Oestrogens

1.
The uterin cycle:
The female sex hormones, estrogen and progesterone, have mumerous functions. The
effect these hormones have on the endometrium of the uterus causes the uterus to undergo
a cyclical series of events known as the uterine cycle . cycles that last 28 days are divided
as follows.
During days 1-5, these is a low level of femal sex hormones in the bady, causing the
uterine lining to disintegrate and its blood vessels to rupture. A flow of blood, known as
the menses, passes out of the vagina during a period of menstruation, also known as the
menstrual period.
During 6-13, increased production of estrogen by an ovarian follicle causes the
endometrium to thicken and to become vascular and glandular. This is called the
proliferative phase of the uterine cycle.
Ovulation usually occurs on the fourteenth day of the 28 day cycle.
During day 15-28, increased production of progesterone by the corpus luteum causes the
endometrium to double in thickness and the uterine glands to mature, producing a thick
mucoid secretion. This is called the secretory phase of the uterine cycle. The endometrium
now is prepared to recive the developing embryo, but if pregnancy dose not occur, the
corpus luteum degenerates and the low level of sex hormones in the female boby causes
the yterine lining to break down. This is evident, due to the menstrual discharge that begins
at this time. Even while menstruation is occurring, the anterior pitutary begins to increase
its production of FSH and a new follical begins to mature.
At about age 45-50, the ovaries gradually cease to respond to the anterior pituitary
hormones. Eventualy,no more follicles are produced. Following this occurrence, called
menopause, menstruationceases entirely.
1.1 Menopause:
More than one third of the women in the United States, about 36 million, have been
through menopause. With a life expectancy of about 81 years, a 50-year-old woman
can expect to live more than one third of her life after menopause.
Scientific research is just beginning to address some of the unanswered
questions about these years and about the poorly understood biology of menopause.
Menopause is the point in a woman's life when menstruation stops permanently,
signifying the end of her ability to have children. Known as the "change of life,"
menopause is the last stage of a gradual biological process in which the ovaries reduce
their production of female sex hormones--a process which begins about 3 to 5 years
before the final menstrual period. This transitional phase is called the climacteric, or
perimenopause. Menopause is considered complete when a woman has been without
periods for 1 year. On average, this occurs at about age 50. But like the beginning of
menstruation in adolescence, timing varies from person to person. Cigarette smokers
tend to reach menopause earlier than nonsmokers.
The Female Reproductive System
Before menopause (left): The detail of the ovary shows the release of the egg into the
fallopian tube
After menopause (right): Notice thinning and shrinking of tissues from decreased
estrogen and progesterone
The ovaries contain structures called follicles that hold the egg cells. You are born
with about 2 million egg cells and by puberty there are about 300,000 left. Only about
400 to 500 ever mature fully to be released during the menstrual cycle.The rest
degenerate over the years. During the reproductive years, the pituitary gland in the
brain generates hormones that cause a new egg to be released from its follicle each
month. The follicle also increases production of the sex hormones estrogen and
progesterone, which thicken the lining of the uterus. This enriched lining is prepared
to receive and nourish a fertilized egg following. .
If fertilization does not occur, estrogen and progesterone levels drop, the lining of the
uterus breaks down, and menstruation occurs.
For unknown reasons, the ovaries begin to decline in hormone production during the
mid-thirties. In the late forties, the process accelerates and hormones fluctuate more,
causing irregular menstrual cycles and unpredictable episodes of heavy bleeding. By
the early to mid-fifties, periods finally end altogether. However, estrogen production
does not completely stop. The ovaries decrease their output significantly, but still may
produce a small amount. Also, another form of estrogen is produced in fat tissue with
help from the adrenal glands (near the kidney). Although this form of estrogen is
weaker than that produced by the ovaries, it increases with age and with the amount
of fat tissue.
Progesterone, the other female hormone, works during the second half of the
menstrual cycle to create a lining in the uterus as a viable home for an egg, and to
shed the lining if the egg is not fertilized. If you skip a period, your body may not be
making enough progesterone to break down the uterine lining. However, your
estrogen levels may remain high even though you are not menstruating.
At menopause, hormone levels don't always decline uniformly. They alternately rise
and fall again. Changing ovarian hormone levels affect the other glands in the body,
which together make up the endocrine system..
2. HORMONS THAT USED AS ORAL CONTRA-CEPTIVE AND
AS HORMON REPLACIMANT THERAPY:
2.1 The progestins:
2.1.1Natural progestins: progesterone:
Progesterone is the most imprtant progestine in humans. In addition to having important
hormonal effects, it serves as a precursor to the estrogens, androgens, and adrenocortical
steroids. It is synthesized in the ovary, testis, and adrenal from circulating cholesterol.
Large amounts are also synthesized and released by the placenta during pregnancy.
In the ovary, progesterone is produced primarily by the corpus luteum. Narmal males
appear to secrete 1-5mg of progesterone dialy, resulting in plasma levels of about 0.03
microgram/dl. The level is only slightly higher in the female during the follicular phase of
the cycle, when oly a few milligrams per day of progesterone are secreted. During the
luteal phase, plasma levels range from 0.5microgram/dl to more than 2microgram/dl.
The resultant Benefits of natural progesterone include
1. Helps Use Fat for Energy
2. Facilitates Thyroid Hormone Action
3. Natural Anti-depressant
4. Natural Diuretic
5. Normalizes Blood Sugar Levels
6. Restores Proper Cell Oxygen Levels
7. Restores Libido
8. Normalizes Zinc & Copper Levels
9. Normalizes Blood Clotting
10. Protects Against Breast Fibrocysts
11. Helps Prevent Breast Cancer
12. Helps Prevent Endometrial Cancer
13. Necessary for Survival of Embryo
14.
Maintains Secretory Endometrium
15. Stimulates Osteoblast Cells (Osteoporosis Reversal)
16.
Precursor for Cortisone Production (Arthritis)
2.1.2Pharmacokinatics:
Progesterone is rapidly absorbed fpllowin administeration by anu route. Its half-life in
the plasma is approximately 5 min, and small amounts are stored temporarily in body
fat. It is almost complrtrly metabolism in on passage through the liver, and for that
reason it is guite inffective when administered orally.
In liver , progesterone is metabolized to pregnanediol and conjugated with glucronic
acid. It is excreted into the urine as pregnanediol in the urine has been used as an index
of progesterone secretion. It has been very useful in spite of the fact that the proportion
of secreted progesterone converted to this compound varies from day to day and from
individual to individual. Most of progesteron are metabolzed to inactive products that
are excreted mainly in the urine.
Gel:
Multiple Dose Pharmacokinetics of Progesterone Gel
Twice daily dosing for 12
Once daily dosing for 12
12 days
days
Cmax (ng/ml)
14.57
15.97
Cavg (ng/ml)
11.6
8.99
Tmax (hr)
3,55
5.4
AUC (ng ‫ں‬hr/ml)
138.72
391.98
t½ (hr)
25.91
45
2.1.3Contraindications:
Hypersensitivity to progestins; thrombophlebitis, thromboembolic disorders, cerebral
hemorrhage or patients with a history of these conditions; impaired liver function or
disease; carcinoma of the breast or genital organs; undiagnosed vaginal bleeding;
missed abortion; as a diagnostic test for pregnancy; prophylactic use to avoid weight
loss (megestrol acetate suspension).
2.1.4 Warnings:
Ophthalmologic effects: Discontinue medication pending examination if there is a
sudden partial or complete loss of vision or if there is sudden onset of proptosis,
diplopia or migraine. If papilledema or retinal vascular lesions occur, discontinue use.
Thrombotic disorders:
Thrombotic disorders (thrombophlebitis, cerebrovascular disorders, retinal thrombosis,
pulmonary embolism) occasionally occur in patients taking progestins; be alert to the
earliest manifestations of the disease. If these occur or are suspected, discontinue the
drug immediately. However, this has not been shown to occur more often than that
seen in a control group.
HIV-infected women:
Although megestrol has been used extensively in women for endometrial and breast
cancers, its use in HIV-infected women has been limited. All the women in the clinical
trials reported breakthrough bleeding.
Precautions:
Pretreatment physical examination: Pretreatment physical examination should include
breasts and pelvic organs, as well as Papanicolaou smear. Advise the pathologist of
progestin therapy when relevant specimens are submitted. In cases of irregular vaginal
bleeding, consider nonfunctional causes. Adequately diagnose all cases of vaginal
bleeding.
fluid retention: Fluid retention may occur; therefore, conditions influenced by this
factor (epilepsy, migraine, asthma, cardiac or renal dysfunction) require careful
observation.
Depression:
Observe patients who have a history of psychic depression and
discontinue the drug if depression recurs to a serious degree.
Glucose tolerance: A decrease in glucose tolerance has been observed in a small
percentage of patients on estrogen-progestin combination drugs. The mechanism of
this decrease is not known. For this reason, carefully observe diabetic patients
receiving progestin therapy.
Menopause: The age of the patient constitutes no absolute limiting factor although
treatment with progestins may mask the onset of the climacteric.
Causes of weight loss: Institute therapy with megestrol for weight loss only after
treatable causes of weight loss are sought and addressed. These treatable causes
include possible malignancies, systemic infections, GI disorders affecting absorption
and endocrine, renal or psychiatric diseases.
Benzyl alcohol:
Benzyl alcohol, contained in some of these products as a
preservative, has been associated with a fatal "gasping syndrome" in premature
infants.
Ethaline ester dioil
Diethale
Stepsterol
Mesternol
Hydroxpro
Medroxw pr
Norethendrom
Norgesterol
Oral
Combbill
2.1.5 Progestins Drug Interactions
Precipitant drug
Object drug*
Aminoglutethimide Medroxyprogesterone
Description
Aminoglutethimide
may increase the
hepatic metabolism
of medroxyprogesterone,
possibly decreasing
its therapeutic effects.
Rifampin
Norethindrone
Rifampin may
reduce the plasma
levels of
norethindrone via
hepatic
microsomal
enzyme
induction,
possibly decreasing its
pharmacologic effects.
=Object drug decreased.
2.1.6adverse reactions
For information concerning adverse reactions associated with combined estrogenprogestin therapy, refer to the Oral Contraceptives group monograph. (Reference)
CNS: Insomnia; somnolence; mental depression.
Dermatologic:
Rash (allergic) with and without pruritus; acne; melasma or
chloasma. Progesterone is irritating at the injection site whether the oil or aqueous
vehicle is used; however, the aqueous preparation is particularly painful.
GI: Changes in weight (increase or decrease); nausea.
GU:
Breakthrough bleeding; spotting; change in menstrual flow; amenorrhea;
changes in cervical eversion, cervical secretions; galactorrhea.
Miscellaneous: Breast changes (tenderness); masculinization of the female fetus;
edema; cholestatic jaundice; pyrexia; hirsutism.
2.2Drugs for progestron:
1.PROGESTERONE
1.1 Prometrium: (Schering-Plough)
Capsules: 100 mg (micronized progesterone)
Glycerin, peanut oil. (SV). Peach. In 100s.
1.2 Progesterone In Oil
Various, eg, Moore, Rugby, Schein, Steris, URL
Injection: 50 mg per ml
In sesame or peanut oil with benzyl alcohol. In 10 ml vials.
1.3 Progesterone
Various, eg, Cyclin, Gallipot
Powder, micronized
In 1, 10, 25, 100 and 1000 g.
1.4 Crinone
Wyeth Labs
Vaginal gel: 8% (90 mg)
Glycerin, mineral oil. In single-use disposable applicator delivering 1.125 g gel.
2.2.1 Administration and Dosage:
Parenteral:
For IM use. The drug is irritating at the injection site. Progesterone is also available
as a micronized powder for prescription compounding
Amenorrhea:
Administer 5 to 10 mg daily for 6 to 8 consecutive days. If ovarian activity has
produced a proliferative endometrium, expect withdrawal bleeding 48 to 72 hours after
the last injection. Spontaneous normal cycles may follow.
Functional uterine bleeding:
Administer 5 to 10 mg daily for 6 doses. Bleeding should cease within 6 days. When
estrogen is also given, begin progesterone after 2 weeks of estrogen therapy.
Discontinue injections when menstrual flow begins.
Gel:
Infertility: For progesterone supplementation or replacement as part of an Assisted
Reproductive Technology (ART) treatment for infertile women with progesterone
deficiency. Administer 90 mg vaginally once daily in women who require
progesterone supplementation. In women with partial or complete ovarian failure who
require progesterone replacement, administer 90 mg vaginally twice daily. If
pregnancy occurs, continue treatment until placental autonomy is achieved, up to 10 to
12 weeks.
2. MEDROXYPROGESTERONE ACETATE
1.Medroxyprogesterone Acetate
Various, eg, Barr, Greenstone, Rugby, Warner Chilcott
Tablets: 2.5 mg
,5mg , 10mg

Cycrin (ESI Lederle)

Provera (Upjohn)
2.1.1Administration and Dosage:
Secondary amenorrhea:
5 to 10 mg daily for 5 to 10 days. A dose for inducing an optimum secretory
transformation of an endometrium that has been adequately primed with either
endogenous or exogenous estrogen is 10 mg daily for 10 days. Start therapy any time.
Withdrawal bleeding usually occurs 3 to 7 days after therapy ends.
Abnormal uterine bleeding:
due to hormonal imbalance in the absence of organic pathology: 5 to 10 mg daily for
5 to 10 days, beginning on the 16th or 21st day of the menstrual cycle. To produce an
optimum secretory transformation of an endometrium that has been adequately primed
with either endogenous or exogenous estrogen, give 10 mg daily for 10 days,
beginning on the 16th day of the cycle. Withdrawal bleeding usually occurs 3 to 7
days after discontinuing therapy. Patients with recurrent episodes of abnormal uterine
bleeding may benefit from planned menstrual cycling with medroxyprogesterone
acetate.
3. HYDROXYPROGESTERONE CAPROATE IN OIL
Hydroxyprogesterone Caproate :
Injection: 125,250 mg per ml
Various, eg, Steris
3.1 Administration and Dosage:
Hydroxyprogesterone, a long-acting progestin, has a 9 to 17 day duration of action.
For IM use.
Amenorrhea (primary and secondary); dysfunctional uterine bleeding; metrorrhagia:
Usual adult dose is 375 mg.
Production of secretory endometrium and desquamation:
Test for continuous
endogenous estrogen production (medical D and C). Usual adult dose is 125 to 250 mg
given on tenth day of cycle; repeat every 7 days until suppression is no longer desired.
4. NORETHINDRONE ACETATE
Example:
Aygestin : tablet 5mg
4.1 Administration and Dosage:
-Amenorrhea; abnormal uterine bleeding due to hormonal imbalance in the absence of
organic pathology: Give 2.5 to 10 mg daily for 5 to 10 days during the second half of
the menstrual cycle.
-Endometriosis: Initial dose is 5 mg/day for 2 weeks; increase in increments of
2.5 mg/day every 2 weeks until 15 mg/day is reached. Therapy may be held at this
level for 6 to 9 months or until breakthrough bleeding demands temporary termination.
5. Estrogens And Progestins Combined
ESTROGENS AND PROGESTINS COMBINED

Prempro: Tablets: 0.625 mg conjugated estrogens/5or
2.5 mg medroxyprogesterone acetat

Premphase: Tablets:0.625 mg conjugated estrogens

Combipatch:
Transdermal
patch:
0.05
mg
estradiol/0.14 mg norethindrone acetate
5.1 Indications:
Treatment of moderate-to-severe vasomotor symptoms associated with
menopause; treatment of vulval and vaginal atrophy; osteoporosis
prevention.
‫ط‬Unlabeled
uses:
May
be
an
effective
alternative
to
treat
hypercholesterolemia in postmenopausal women (0.3 to 1.25 mg
conjugated estrogens with 5 mg medroxyprogesterone).
5.1.1 Administration and Dosage:
The oral recommended dose is either:

One 0.625 mg/2.5 mg tablet once daily, or

One 0.625 mg conjugated estrogen tablet once daily on days 1
through 14 and one 0.625 mg conjugated estrogen/5 mg
medroxyprogesterone tablet taken once daily on days 15 through
28.
-Menopause and vulval/vaginal atrophy: Re-evaluate patients at 3- to 6month intervals to determine need for continued treatment.
-Osteoporosis: Monitor patients with an intact uterus closely for signs of
endometrial cancer; evaluate recurrent or persistent abnormal vaginal
bleeding appropriately to rule out malignancy. The mainstays of prevention
and management of osteoporosis are estrogen and calcium; exercise and
nutrition may be important adjuncts.
3. Contraceptive Hormones
ORAL CONTRACEPTIVES
3.1Warning:
Smoking: Cigarette smoking increases the risk of serious cardiovascular
side effects from OCs. This risk increases with age and with heavy
smoking (>= 15 cigarettes per day) and is quite marked in women > 35
years of age. Women who use OCs should not smoke.
3.2 Indications:
Contraception: For the prevention of pregnancy.
Because of the positive association between the amount of estrogen and
progestin in OCs and the risk of vascular disease and thromboembolism,
minimizing exposure to these agents is in keeping with good principles of
therapeutics. For any particular combination, prescribe the dosage regimen
that contains the least amount of estrogen and progestin compatible with a
low failure rate and needs of the individual patient. Start new patients on
preparations containing <= 35 mcg estrogen.
Emergency contraception:
For prevention of pregnancy following
unprotected intercourse or a known or suspected contraceptive failure. To
obtain efficacy, the first dose should be taken as soon as possible within 72
hours of intercourse. The second dose must be taken 12 hours later.
Acne vulgaris (Ortho Tri-Cyclen only): For the treatment of moderate acne
vulgaris in females >= 15 years of age who have no known
contraindications to oral contraceptive therapy, desire contraception, have
achieved menarche, and are unresponsive to topical antiacne medications.
3.3 Administration and Dosage:
Product choice: Only low-dose pills should be routinely used; there is
rarely a need for > 50 mcg estrogen component tablets.
Acne: The timing of dosing with Ortho Tri-Cyclen for acne should follow
the guidelines for use of Ortho Tri-Cyclen as an OC. The dosage regimen
for treatment of facial acne uses a 21-day active and a 7-day inert schedule.
Take 1 active tablet daily for 2 1days followed by 1 inert for 7 days. After
28 tablets have been taken, a new course is started the next day.
3.4 Contraception:
Progestin-only:
One tablet every day at the same time. Administration is continuous, with
no interruption between pill packs. Every time a pill is taken late,
especially if a pill is missed, pregnancy is more likely.
Missed dose: If the patient is > 3 hours late or misses >= 1 tablet, she
should take a missed pill as soon as remembered, then go back to taking
POPs at the regular time, but be sure to use a backup method (such as a
condom or spermicide) every time she has sexual intercourse for the next
48 hours.
combination OCs:
Combination OCs inhibit ovulation by suppressing the gonadotropins,
FSH, and LH. Additionally, alterations in the genital tract, including
cervical mucus (which inhibits sperm penetration) and the endometrium
(which
reduces the likelihood of implantation), may contribute to
contraceptive effectiveness.
These products differ in the type and relative potency of the components
and in the relative predominance of estrogenic or progestational activity.
Their ultimate effects are related to combined estrogenic, progestational,
androgenic, and anti-estrogenic effects.
Progestins may modify the effects of estrogens; these effects depend on the
type or amount of progestin present and the ratio of progestin to estrogen.
Dosage, potency, length of administration, and concomitant estrogen
administration contribute to total progestational potency, making it difficult
to establish equivalent doses of progestins. The total estrogenic potency of
an OC is based on the combined effects of the estrogen and the
estrogenic/antiestrogenic/androgenic effect of the progestin.
3.5 Achieving Proper Hormonal Balance In An Oral
Contraceptive
Estrogen
- Excess

Nausea, bloating

Cervical mucorrhea, polyposis

Melasma

Hypertension

Migraine headache

Breast fullness or tenderness

Edema
-Deficiency

Early or mid-cycle breakthrough bleeding

Increased spotting

Hypomenorrhea
Progestin:
- Excess

Increased appetite

Weight gain

Tiredness, fatigue

Hypomenorrhea

Acne, oily scalp 1

Hair loss, hirsutism 1

Depression

Monilial vaginitis

Breast regression
-Deficiency

Late breakthrough bleeding

Amenorrhea

Hypermenorrhea
4.The estrogens:
Estrogenic activity is shared by a large number of chemical substances.
In addition to the variety of steroidal estrogens derived from animal sources, numerous
nonsteroidal estrogens have been synthesized. Many phenols are estrogenic, and
estrogenic activity has been identified in such diverse froms of life as those found in
the sediments of the seas. Estrogen are found in many plants, including soy beans and
other foods. However, studies fail to show that eating them produces significant
estrogenic effects.
4.1 Pharmacokinetics:
When released into the circulation. Estradiol binds strongly to alpha2-globulin ( sex
hormone binding globulin) and to albumin with less affinity. bound estrogen is
relatively unavailable for diffusion in to cells, so it is the free fraction that is
physiologically active. Estradiol is converted by the liver and other tissue to estrone
and estriol (which have low affinity for the estrogen receptor ) and their 2hydroxylated derivatives and conjugated metabolism (whish are too insoluble in lipid
to cross the cell membrane readily) and excreted in the bile. How ever, the conjugates
may be hydrolyzed in the intestine to active, reabsorbable compounds. The catechol
estrogens serve as neurotransmitters in the central nervous system. They are converted
to 2-and 4- methoxy compounds by catechol-o-methyl transferase and in high
concentrations can inhibit the inactivation of catecholamine by the enzyme. Estrogens
are also excreted in small amounts in the breast milk of nursing mothers.
Because significant amounts of estrogens and their active metabolites
are excreted in the bile and reabsorbed from the intestine. The resulting enterohepatic
circulation ensures that orally administered estrogens will have a high ratio of hepatic
to peripheral effects. As noted below, the hepatic effects are thought to be responsible
for some undesirable actions such as synthesis of increased clotting factors and plasma
renin substrate. When used for their peripheral effects- eg, in postmenopausal women
the hepatic effects can be minimized by routes that avoid first pass hepatic exposure,
ie, vaginal, Because significant amounts of estrogens and their active metabolites
transdermal, or by injection.
4.2 Pharmacology –
Although 6 different natural estrogens have been isolated from the human female, only
3 are present in significant quantities: 17 b-estradiol, estrone, and estriol. The most
potent and major secretory product of the ovary, estradiol, is rapidly and reversibly
oxidized to estrone. Both of these can be converted to the much weaker estriol. The
estrogenic potency of estradiol is 12 times estrone's and 80 times estriol's. Estradiol's
potency is increased even more by the addition of an ethinyl substitution which
inhibits its first-pass metabolism.
Estrogens, important in developing and maintaining female reproductive system and
secondary sex characteristics, promote growth and development of the vagina, uterus,
fallopian tubes, and breasts. They affect release of pituitary gonadotropins; cause
capillary dilatation, fluid retention, protein anabolism, increase water content of
cervical mucus, and inhibit ovulation. Indirectly, they contribute to the following:
Shaping of the skeleton; maintenance of tone and elasticity of urogenital structures;
changes
in epiphyses of long bones that allow for pubertal growth spurt and its termination;
growth of axillary and pubic hair; pigmentation of nipples and genital
Metabolism/Execretion: Metabolism and inactivation occur primarily in the liver.
During cyclic passage through the liver, estrogens are degraded to less active
estrogenic compounds.
Some estrogens are excreted into bile, reabsorbed from
intestines, and returned to the liver via the portal venous system. Water-soluble
estrogen conjugates, strongly acidic, are ionized in body fluids, which favor excretion
through the kidneys; tubular reabsorption is minimal.
4.3 Contraindications:
Breast cancer, except in appropriately selected patients being treated for metastatic
disease; estrogen-dependent neoplasia; undiagnosed abnormal genital bleeding; active
thrombophlebitis or thromboembolic disorders; history of thrombophlebitis,
thrombosis or thromboembolic disorders associated with previous estrogen use (except
when used in treatment of breast or prostatic malignancy); known or suspected
pregnancy (see Warning Box); hypersensitivity to any product component.
Warning:
Estrogens have been reported to increase the risk of endometrial carcinoma in
postmenopausal women: Studies have shown an increased risk of endometrial cancer
in postmenopausal women exposed to exogenous estrogens for prolonged periods. The
risk of endometrial cancer in estrogen users was 4.5 to 13.9 times greater than in
nonusers and appears to depend on duration of treatment and dose. Therefore, when
estrogens are used for the treatment of menopausal symptoms, use the lowest dose and
discontinue medication as soon as possible. When prolonged treatment is indicated,
reassess the patient at least semiannually by endometrial sampling to determine the
need for continued therapy. Cyclic administration of low doses of estrogen may carry
less risk than continuous administration.
Close clinical surveillance of women taking estrogens is important. In undiagnosed
persistent or recurring abnormal vaginal bleeding, exclude malignancy.
There is no evidence that "natural" estrogens are more or less hazardous than
"synthetic" estrogens at equiestrogenic doses.
Do not use estrogens during pregnancy:
Estrogen therapy during pregnancy is
associated with an increased risk of congenital defects in the reproductive organs of
the fetus and possibly other birth defects. Studies of women who received
diethylstilbestrol (DES) during pregnancy have shown that female offspring have an
increased risk of vaginal adenosis, squamous cell dysplasia of the uterine cervix, and
clear cell vaginal cancer later in life; male offspring have an increased risk of
urogenital abnormalities and possibly testicular cancer later in life.
There is no indication for estrogen therapy during pregnancy or during the immediate
postpartum period. Estrogens are ineffective for the prevention or treatment of
threatened or habitual abortion.
If estrogens are used during pregnancy, or if the patient becomes pregnant while
taking estrogens, inform her of the potential risks to the fetus.
4.4 What is Estrogen Dominance?
For the first two weeks of a woman's monthly estrogen is supposed to be the dominant
hormone. Then, in response to ovulation, progesterone is supposed to rise and assume
dominance for the final two weeks. Normally the menstrual cycle begins a day or two
after progesterone levels fall.
However, when progesterone levels fail to reach the normal 22 - 25 mg. during the
final two weeks of a woman's monthly cycle then estrogen is unopposed for the entire
month and this condition is referred to as "Estrogen Dominance."
The symptoms of PMS & menopause and the conditions of infertility & osteoporosis
have been shown to be the result of "Estrogen Dominance" relative to an insufficiency
of natural progesterone.
PROGESTINS. Although these drugs are commonly referred to as progesterone, this
is a misnomer. In some ways they mimic the effects of progesterone in the body, but in
other important ways they gravely interfere with natural progesterone and can create
and exacerbate hormone related health problems, and be a primary contributor to the
condition referred to as Estrogen Dominance:

Increased Body Fat

Interference with Thyroid Hormone Activity (hypothyroid)

Depression & Headaches

Salt and Water Retention

Blood Sugar Irregularities (Food Cravings)

Reduced Oxygen in All Cells

Decreased Libido (Sex Drive)

Loss of Zinc and Retention of Copper

Excessive Blood Clotting

Increased Risk of Breast Cancer

Reduced Vascular Tone

Increased Risk of Endometrial Cancer

Endometriosis

Uterine Cramping

Infertility

Increased Risk of Uterine Cancer
4.5 indications:
Estrogens are most commonly used as a component of combination contraceptives or
as
hormone
replacement
therapy in
postmenopausal
women.
Benefits
in
postmenopausal women include relief of moderate-to-severe vasomotor symptoms,
decreased risk of osteoporosis and cardiovascular disease. Hormone replacement
therapy may also be used in female hypogonadism, castration, or primary ovarian
failure. Less commonly, select breast or prostate cancer patients with advanced disease
may receive estrogens as palliative therapy. Refer to individual agents for specific
indications.
Unlabeled uses:
A 5 mcg ethinyl estradiol tablet is being investigated for use in the treatment of
Turner's syndrome.
4.5 Administration and Dosage:
Given cyclically for short-term use only:
For treatment of moderate-to-severe
vasomotor symptoms, atrophic vaginitis, or kraurosis vulvae associated with
menopause, administer the lowest effective dose; discontinue medication as promptly
as possible. Administration should be cyclic (eg, 3 weeks on and 1 week off). Attempt
to discontinue or taper medication at 3- to 6-month intervals.
Cyclical: Female hypogonadism or castration; primary ovarian failure; osteoporosis.
Chronic:
Inoperable progressing prostatic cancer; inoperable progressing breast
cancer in appropriately selected men and postmenopausal women.
Continued therapy with estrogen alone may induce functional uterine bleeding.
4.6 concomitant progestin therapy:
Addition of a progestin for 10 to 13 or more days of a cycle of estrogen has lowered
the incidence of endometrial hyperplasia. Morphological and biochemical studies of
endometrium suggest that 10 to 14 days of progestin are needed to provide maximal
maturation of the endometrium and to eliminate any hyperplastic changes. It is not
established whether this will provide protection from endometrial carcinoma. There
may be additional risks with the inclusion of progestin in estrogen replacement
regimens, including adverse effects on carbohydrate and lipid metabolism (lowering
HDL and raising LDL) which could diminish the purported cardioprotective effect of
estrogen therapy; impairment of glucose tolerance; possible enhancement of mitotic
activity in breast epithelial tissue, although few epidemiological data are available to
address this point. Choice of progestin, cyclic or continuous mode, and dosage may
be important in minimizing risks.
Monitor treated patients with an intact uterus closely for signs of endometrial cancer,
and take appropriate diagnostic measures to rule out malignancy in the event of
persistent or recurring abnormal vaginal bleeding.
4.6.1 Adverse Reactions:
See Warnings regarding induction of neoplasia, adverse effects on the fetus, increased
incidence of gallbladder disease, hypercalcemia, cardiovascular disease, elevated
blood pressure, and adverse effects similar to those of OCs.

CNS:
Headache; migraine; dizziness; mental depression;
chorea; insomnia; anxiety; migraine; emotional lability.

Dermatologic: Chloasma or melasma (may persist when drug is
discontinued); erythema nodosum/multiforme; hemorrhagic eruption;
dermatitis; skin hypertrophy; loss of scalp hair; hirsutism; pruritus.

GI:
Nausea; vomiting; abdominal cramps/pain; bloating;
cholestatic jaundice; colitis; acute pancreatitis; diarrhea; dyspepsia;
flatulence; gastritis; gastroenteritis; enlarged abdomen; hemorrhoids.

GU:
Breakthrough bleeding; withdrawal bleeding; spotting;
change in menstrual flow; dysmenorrhea; premenstrual-like syndrome;
amenorrhea during and after treatment; vaginal candidiasis; change in
cervical erosion and degree of cervical secretion; cystitis-like
syndrome;
hemolytic
uremic
syndrome;
endometrial
cystic
hyperplasia; urinary tract infection; leukorrhea; vaginitis; vaginal
discomfort/pain; vaginal hemorrhage; asymptomatic genital bacterial
growth; genital moniliasis; cystitis; dysuria; genital pruritus; genital
eruption; urinary incontinence; endometrial hyperplasia; increase in
size of uterine leiomyomata/fibromyomata.

Local: Pain at injection site; sterile abscess; postinjection flare;
redness and irritation at application site with the estradiol transdermal
system (17%); rash (rare).

Ophthalmic: Steepening of corneal curvature; intolerance to
contact lenses.

Miscellaneous: Aggravation of porphyria; edema; changes in
libido; breast pain, tenderness, enlargement, or secretion; reduced
carbohydrate tolerance; pain; venous thromboembolism; pulmonary
embolism; hypersensitivity reactions; increase or decrease in weight;
back pain; arthritis; arthralgia; skeletal pain; upper respiratory tract
infection; sinusitis; rhinitis; pharyngitis; flu-like symptoms; hot flushes;
allergy; bronchitis; chest pain; leg edema; otitis media; toothache; tooth
disorder; infection; accidental injury; asthenia; anemia; syncope;
hyperlipidemia; paresthesia..
4.6.2 Overdosage:
Serious ill effects have not been reported following ingestion of large doses of
estrogen-containing OCs by young children. Overdosage of estrogen may cause
nausea; withdrawal bleeding may occur in females.
4.6.3 Patient Information:
Patient package insert is available with products.
Notify physician if any of the following occur: Pain in the groin or calves; sharp
chest pain or sudden shortness of breath; abnormal vaginal bleeding; missed menstrual
period or suspected pregnancy; lumps in the breast; sudden severe headache, dizziness
or fainting; vision or speech disturbance; weakness or numbness in an arm or leg;
severe abdominal pain; yellowing of the skin or eyes; severe depression.
4.7 ESTRONE
Rx
Estrone Aqueous
Injection: 5 mg per ml
In 10 ml vials.
Various)
Rx
Kestrone 5
In 10 ml multi-dose vials. 1
With sodium carboxymethylcellulose, povidone, benzyl alcohol, and methyland propylparabens.
For complete prescribing information, refer to the Estrogens group monograph.
4.7.1 Indications:
Moderate-to-severe vasomotor symptoms associated with menopause; atrophic
vaginitis; kraurosis vulvae; female hypogonadism; female castration; primary ovarian
failure; breast cancer (for palliation only) in appropriately selected women and men
with metastatic disease; prostatic carcinoma (for palliative therapy of advanced
disease).
4.7.2 Administration and Dosage:
Administer IM only. Shake vial and syringe well prior to withdrawal and injection
(using a 21- to 23-gauge needle) to properly suspend medication.
Abnormal uterine bleeding due to hormone imbalance: May respond to brief courses
of intensive therapy. Usual dose range is 2 to 5 mg daily for several days.
Cyclically (eg, 3 weeks on and 1 week off):
Replacement therapy of estrogen deficiency associated conditions (eg, menopausal
vasomotor symptoms, hypogonadism, female castration, primary ovarian failure):
Initial relief of symptoms may be achieved through the administration of 0.1 to 1 mg
of estrone weekly in single or divided doses. Some patients may require 0.5 to 2 mg
weekly. Choose the lowest dose that will control symptoms and discontinue
medication as promptly as possible. Make attempts to discontinue or taper medication
at 3- to 6-month intervals.
Senile vaginitis and kraurosis vulvae: Generally, 0.1 to 0.5 mg 2 or 3 times/week.
Chronically:
Inoperable progressing prostatic cancer: For palliation in prostatic cancer, use estrone
at 2 to 4 mg, 2 or 3 times per week. If a response to therapy is going to occur, it should
be apparent within 3 months of beginning therapy. If a response does occur, continue
the hormone until the disease is again progressive.
4.7.3 Drug Interactions:
Estrogens presumably have similar drug interactions to those observed with oral
contraceptives. Refer to drug interaction section in the Oral Contraceptives
(Reference) group monograph for more information.
Estrogen Drug Interactions
Precipitant drug
Object drug*
Estrogens
Anticoagulants, oral
Description
Estrogens may theoretically
reduce the hypoprothrombinemic effect of anticoagulants.
Estrogens
Antidepressants,
Pharmacologic effects of these
tricyclic
agents may be altered by
estrogens; the effects of this
interaction may depend on the
dose of the estrogen. An
increased incidence of toxic
reactions may also occur.
P450 inducers
Estrogens
Coadministration of barbiturates,
Barbiturates
rifampin, and other agents that
Rifampin
induce hepatic microsomal
enzymes may produce lower
estrogen levels than expected.
Estrogens
Corticosteroids
An increase in the
pharmacologic
effects
and
toxicologic
of corticosteroids
may
occur via
inactivation of hepatic
P450 enzyme.
Hydantoins
Estrogens
Breakthrough bleeding,
spotting, and pregnancy have
resulted
when these medications
were used concurrently. A loss of
seizure control has also been
suggested
and may be due to fluid retention.
= Object drug increased. = =object drug decreased.
= Undetermined clinical effect.
4.8 ESTRADIOL TRANSDERMAL SYSTEM
Product/Distributor
Release rate
mg/24 hr
surface area
cm2
Total estradiol content
mg
Supplied
FemPatch
Parke-Davis
0.025
30
10.3
In4s
How
Vivelle
Ciba-Geigy
0.0357
11
3.28
In calendar packs
(8 and 24 systems).
Vivelle-Dot
Novartis
3.57
0.585
In calendar packs (8 systems).
4.8.1Indications:
Moderate-to-severe vasomotor symptoms associated with menopause; female
hypogonadism; female castration; primary ovarian failure; atrophic conditions caused
by deficient endogenous estrogen production, such as atrophic vaginitis and kraurosis
vulvae; atrophic urethritis; prevention of osteoporosis (loss of bone mass); abnormal
uterine bleeding due to hormonal imbalance in the absence of organic pathology and
only when associated with a hypoplastic or atrophic endometrium.
4.8.2 Administration and Dosage:
Initiation of therapy:
Treatment of menopausal symptoms:
Initiate therapy with the lowest dosage
necessary to control symptoms, especially in women with an intact uterus, (eg, 0.025
to 0.05 mg) applied to skin twice weekly. Adjust dose as necessary to control
symptoms. Attempt to taper or discontinue the drug at 3- to 6-month intervals.
Prophylaxis to prevent postmenopausal bone loss: Initiate with 0.05 mg/day as soon
as possible after menopause. Adjust dosage if necessary to control concurrent
menopausal symptoms. Discontinuation may reestablish natural bone loss rate.
In women who are not taking oral estrogens, start treatment immediately. In women
who are currently taking oral estrogens, start treatment 1 week after withdrawal of oral
therapy or sooner if symptoms reappear in < 1 week.
4.8.3 Therapeutic regimen:
Therapy may be given continuously in patients who do not have an intact uterus. In
patients with an intact uterus, therapy may be given on a cyclic schedule (eg, 3 weeks
therapy followed by 1 week off).
Alora, Estraderm, Esclim, and Vivelle are applied twice a week; Climara and
FemPatch last for 7 days.
Studies of the addition of a progestin for >= 7 days of a cycle of estrogen use show a
lowered incidence of endometrial hyperplasia. Studies of endometrium suggest that 10
to 14 days of progestin are needed to provide maximal maturation of the endometrium
and to eliminate any hyperplastic changes. Whether this will provide protection from
endometrial carcinoma has not been clearly established. Additional risks, including
adverse effects on lipid metabolism, impairment of glucose tolerance, and possible
enhancement of mitotic activity in breast epithelial tissue may be associated with the
inclusion of progestin in estrogen replacement regimens. The choice of progestin and
dosage may be important in minimizing these adverse effects.
4.8.4 Application of system:
Place adhesive side of the system on a clean, dry area of the skin on buttocks,
abdomen, femoral triangle (upper inner thigh), or upper arm. Do not apply to breasts
or to a site exposed to sunlight. Rotate application site with a >-1 =week interval
between applications to a particular site. The area should not be oily, damaged, or
irritated. Avoid the waistline, since tight clothing may rub the system off. Apply the
system immediately after opening the pouch and removing the protective liner. Press
firmly in place with the palm for » 10 seconds. Make sure there is good contact,
especially around the edges. In the unlikely event that a system falls off, reapply the
same system. If necessary, apply a new system. In either case, continue the original
treatment schedule.
4.9 ESTRADIOL
1. Estradiol, oral
Tablets: 0.5 mg micronized estradiol
In 100s
(Teva)
a.Estrace
Lactose. (021 MJ). White, scored. In 100s
(Bristol-Myers Squibb)
b.Gynodiol (Fielding)
Lactose. (0768). Lavendar, bisected. In
30s
and 100s.
2.Gynodiol(fielding)
Tablets: 1.5 mg micronized estradiol
Lactose.
(0158). Aqua, bisected. In 30s and 100s.2.
4.9.1 Indications:
For the treatment of moderate-to-severe vasomotor symptoms associated with
menopause; vulval and vaginal atrophy; hypoestrogenism due to hypogonadism,
castration, or primary ovarian failure; breast cancer (for palliation only) in
appropriately selected women and men with metastatic disease; advanced androgendependent prostate carcinoma (for palliation only); osteoporosis prevention.
4.9.2 Administration and Dosage:
Moderate-to-severe vasomotor symptoms, vulval/vaginal atrophy associated with
menopause, female hypogonadism, female castration, primary ovarian failure: Use the
lowest dose and regimen that will control symptoms and discontinue medication as
promptly as possible. Attempt to discontinue or taper medication at 3- to 6-month
intervals.
Initiate treatment with 1 or 2 mg/day; adjust to control presenting symptoms. Titrate to
determine the minimal effective dose for maintenance therapy.
Prostatic cancer (androgen-dependent, advanced): For palliation only. Administer 1
to 2 mg 3 times daily. Judge the effectiveness of therapy by phosphatase
determinations and by symptomatic improvement of the patient.
Breast cancer, metastatic: For palliation only. Given in appropriately selected men
and women, the usual dose is 10 mg 3 times daily for >= 3 months.
Osteoporosis prevention: Administer cyclically (eg, 23 days on and 5 days off) 0.5
mg/day as soon as possible after menopause. Adjust dosage if necessary to control
concurrent menopausal symptoms. Discontinuation may re-establish natural rate of
bone loss. The mainstays of prevention and management of osteoporosis are estrogen
and calcium; exercise and nutrition may be important adjuncts.
4.10 ESTRADIOL VALERATE IN OIL
1. delesteron :
Injection: 10 mg/ml
In 5 ml multi-dose vials. 1

Estradiol Valerate
Various, eg, Schein, Steris
Injection: 20 mg/ml
In 10 ml vials.

delestron
Bristol-Myers Squibb
In 5 ml multidose vials. 2

Gynogen L.A. 20
Forest
In 10 ml multi-dose vials. 2

Valergen 20
Hyrex
In 10 ml multi-dose vials. 2
2. Estradiol Valerate
Various, eg, IDE, Schein, Steris, Zenith-Goldline
Injection: 40 mg/ml
In 10 ml vials.

Estra-L 40
Taylor
In 10 ml vials. 2

Delestrogen
Bristol-Myers Squibb
In 5 ml multidose vials. 2

Valergen 40
Hyrex
In 10 ml multi-dose vials. 2
4.10.1 Indications:
For the treatment of moderate-to-severe vasomotor symptoms associated with
menopause; atrophic vaginitis; kraurosis vulvae; female hypogonadism; female
castration; primary ovarian failure; prostatic carcinoma (inoperable, progressing; for
palliation therapy).
Administration and Dosage:
For IM injection only.
Moderate-to-severe vasomotor symptoms, atrophic vaginitis, or kraurosis vulvae
associated with menopause: For short-term use only. 10 to 20 mg every 4 weeks.
Female hypogonadism, female castration, or primary ovarian failure: 10 to 20 mg
every 4 weeks given cyclically.
Prostatic carcinoma: >= 30 mg every 1 or 2 weeks.
4.11 CONJUGATED ESTROGENS
Rx
Premarin
Wyeth-Ayerst
Tablets: 0.3 mg
Lactose, sucrose. Green. Oval. In
100s and 1000s.
0.625mg
sucrose. Maroon. Oval. In 100s, 1000s, 5000s, and UD 100s.
0.9mg
Lactose, sucrose. White. Oval. In 100s.
1.5mg
Lactose, sucrose. Yellow. Oval. In 100s, 1000s, 5000s, and UD
100s.
2.5mg
Lactose, sucrose. Purple. Oval. In 100s and 1000s.
Rx
Premarin Intravenous
Wyeth-Ayerst
Injection: 25 mg conjugated estrogens
In Secules 1 (vials), each with 5 ml sterile diluent. 2
4.11.1 Indications:
Oral: Moderate-to-severe vasomotor symptoms associated with menopause; atrophic
vaginitis; osteoporosis (loss of bone mass); hypogonadism; castration; primary ovarian
failure; breast cancer (for palliation only) in appropriately selected women and men
with metastatic disease; prostatic carcinoma (for palliation only; advanced androgendependent).
Parenteral: For the treatment of abnormal uterine bleeding due to hormonal imbalance
in the absence of organic pathology.
4.11.1 Administration and Dosage:
Oral:
Moderate-to-severe vasomotor symptoms associated with menopause: 1.25 mg/day. If
the patient has not menstruated in >= 2 months, start cyclic administration arbitrarily.
If the patient is menstruating, begin administration on day 5 of bleeding.
Atrophic vaginitis and atrophic urethritis associated with menopause: 0.3 to 1.25 mg
or more daily, depending on tissue response of the patient. Administer cyclically (3
weeks of daily estrogen and 1 week off).
Female hypogonadism: 2.5 to 7.5 mg daily, in divided doses for 20 days, followed by
a rest period of 10 days. If bleeding does not occur by the end of this period, repeat
dosage schedule. The number of courses of estrogen therapy necessary to produce
bleeding may vary, depending on the responsiveness of the endometrium.
If bleeding occurs before the end of the 10-day period, begin a 20-day estrogenprogestin cyclic regimen with 2.5 to 7.5 mg estrogen daily in divided doses for 20
days. During the last 5 days of estrogen therapy, give an oral progestin. If bleeding
occurs before this regimen is concluded, discontinue therapy and resume on day 5 of
bleeding.
Female castration and primary ovarian failure: 1.25 mg/day cyclically (3 weeks on, 1
week
off). Adjust according to severity of symptoms and patient response. For maintenance,
adjust to lowest effective level.
Osteoporosis: 0.625 mg/day, cyclically (3 weeks on, 1 week off). The mainstays of
prevention and management of esteoporosis are estrogen and calcium; exercise and
nutrition may be important adjuncts.
Breast carcinoma (for palliation) in appropriately selected women and men with
metastatic disease: 10 mg 3 times daily for >= 3 months.
Prostatic carcinoma (for palliation; advanced androgen-dependent): 1.25 to 2.5 mg 3
times daily. Effectiveness can be judged by phosphatase determinations as well as by
symptomatic improvement.
Parenteral: Treatment of abnormal uterine bleeding due to hormonal imbalance in the
absence of organic pathology. Administration IV produces a more rapid response and
is preferred. Usual dose is one 25 mg injection IV or IM. Repeat in 6 to 12 hours if
necessary. Inject slowly to obviate the occurrence of flushes.
Compatibility:
Infusion of conjugated estrogens with other agents is not
recommended. In emergencies, however, when an infusion has already been started,
make the injection into the tubing just distal to the infusion needle. Solution is
compatible with normal saline, dextrose, and invert sugar solutions. It is not
compatible with protein hydrolysate, ascorbic acid, or any solution with an acid pH.
Storage/Stability:
Before reconstitution, refrigerate at 2o to 8oC (36o to 46oF). Use the reconstituted
solution within a few hours. Refrigerated reconstituted solution is stable for 60 days.
Do not use if darkening or precipitation occurs.
4.12 Selective Estrogen Receptor Modulator
RALOXIFENE
Rx
Evista (Eli Lilly)
Tablets: 60 mg
Lactose. (LILLY 4165). White, elliptical. Film
coated. In 30s, 100s and 2000s.
4.12.1 Indications:
Osteoporosis, prevention: Prevention of osteoporosis in postmenopausal women.
4.12.2 Administration and Dosage:
Approved by the FDA: December 9, 1997.
The recommended dosage is 60 mg daily, which may be administered any time of day
without regard to meals. The effect of raloxifene on bone mineral density (BMD)
beyond 2 years of treatment is not known at this time, but is being evaluated in
ongoing clinical trials.
4.12.3 Actions:
Pharmacology - Raloxifene is a selective estrogen receptor modulator (SERM) that
belongs to the benzothiophene class of compounds. It reduces resorption of bone and
decreases overall bone turnover as evidenced by reductions in serum and urine levels
of bone turnover markers, radiocalcium kinetics studies for decreased bone resorption
and increases in BMD.
Decreases in estrogen levels after oophorectomy or menopause lead to increases in
bone resorption and bone loss. Bone is initially lost rapidly because the compensatory
increase in bone formation is inadequate to offset resorptive losses. This imbalance
between resorption and formation is related to loss of estrogen, and may also involve
age-related impairment of osteoblasts or their precursors.
Raloxifene's biological actions, like those of estrogen, are mediated through estrogen
receptor binding, which results in differential expression of multiple estrogenregulated genes in different tissues. Recent data suggest that the estrogen receptor can
regulate gene expression by at least two distinct pathways that are ligand-, tissue- or
gene-specific.
Clinical data indicate that raloxifene has estrogen-like effects on bone (increase in
BMD) and on lipid (decrease in total and LDL cholesterol levels) metabolism.
Raloxifene is an estrogen antagonist and lacks estrogen-like effects in uterine and
breast tissues.
4.12.4 Warnings:
Venous thromboembolic events: An analysis of raloxifene-treated women showed
an increased risk of venous thromboembolic events defined as deep vein thrombosis,
pulmonary embolism and retinal vein thrombosis. The greatest risk for
thromboembolic events occurs during the first 4 months of treatment. Discontinue
raloxifene at least 72 hours prior to and during prolonged immobilization (eg, postsurgical recovery, prolonged bed rest), and resume therapy only after the patient is
fully ambulatory. Advise patients to avoid prolonged restrictions of movement during
travel. Consider the risk-benefit balance in women at risk of thromboembolic disease
for other reasons, such as congestive heart failure and active malignancy.
Osteoporosis risk: No single clinical finding or test result can quantify risk of
postmenopausal osteoporosis with certainty. However, clinical assessment can help to
identify women at increased risk. Widely accepted risk factors include Caucasian or
Asian descent, slender body build, early estrogen deficiency, smoking, alcohol
consumption, low calcium diet, sedentary lifestyle and family history of osteoporosis.
Evidence of increased bone turnover from serum and urine markers and low bone
mass (eg, at least 1 standard deviation below the mean for healthy, young adult
women) as determined by densitometric techniques are also predictive. The greater the
number of clinical risk factors, the greater the probability of developing
postmenopausal osteoporosis.
Premenopausal use: There is no indication for premenopausal use of raloxifene. Safety of
raloxifene in premenopausal women has not been established and its use is not recommended.
5. Hormone replacment therapy:
To combat the symptoms associated with falling estrogen levels, doctors have turned
to hormone replacement therapy (HRT). HRT is the administration of the female
hormones estrogen and progesterone. Estrogen replacement therapy (ERT) refers to
administration of estrogen alone. The hormones are usually given in pill form, though
sometimes skin patches and vaginal creams (just estrogen) are used. ERT is thought to
help prevent the devastating effects of heart disease and osteoporosis, conditions that
are often difficult and expensive to treat once they appear. Coronary heart disease:
Estrogen replacement therapy is associated with a decrease in the incidence of CHD
and cardiovascular mortality in postmenopausal women. The risk of CHD in
postmenopausal estrogen users has been estimated to be » 50% less than non-users.
Estrogen therapy has been associated with less coronary occlusion in postmenopausal
women undergoing coronary angiography. An apparent cardioprotective benefit of
estrogen is an increase in HDL. Other benefits may be due to estrogen's direct effect
on the arterial wall or indirect actions via increased prostacyclin production, which
results in vasodilation and decreased platelet adhesiveness.
The use of estrogen replacement in postmenopausal women for preventing
cardiovascular disease and death is supported by most studies.
Hormone treatment for menopause is still quite controversial. Its long-term safety
and efficacy remain matters of great concern. There is not enough existing data for
physicians to suggest that HRT is the right choice for all women. Several large studies
are currently attempting to
resolve the questions, though it will take several more years to reach any definitive
answers.
In the 1940's when estrogen was first offered to menopausal women, it was given
alone and in high doses. Today, after 50 years of trial and error, it is well known that
estrogen stimulates growth of the inner lining of the uterus (endometrium) that sheds
during menstruation. This growth may continue uncontrollably, resulting in cancer.
Today, doctors typically prescribe a lower dose of estrogen. However, few doctors
still prescribe estrogen alone to women who have a uterus.
Most now prefer to add a synthetic form of progesterone called progestin to
counteract estrogen's dangerous effect on the uterus. Progestin reduces the risk of
cancer by causing monthly shedding of the endometrium. The obvious drawback to
this approach is that menopausal women resume monthly bleeding. Once menopause
arrives, most women enjoy the freedom of life without a period. Many are reluctant to
begin their cycles again. In addition, there are other unpleasant side effects of
progestin which often discourage women from continuing HRT. These include breast
tenderness, bloating, abdominal cramping, anxiety, irritability, and depression.