Download Female Sex Hormones

Sex Hormones
Female Sex Hormones
(Estrogens and Progestins)
Estrogens

Natural Estrogens:
OH
OH
O
OH
HO
HO
17-estradiol
HO
Estrone
Estriol
Structure Activity Relation Ships
 Aromatic ring with C-3-OH is essential for activity.
 Steroidal structures is not essential for activity.
 Alkylation of the aromatic ring decrease the activity.
 Unsaturation of ring B decreases the activity.
 17α- and 16 position when modified enhance the activity.
OH
OH
O
OH
HO
HO
17-estradiol
HO
Estrone
Estriol
Physiological Effects



Development of the female sexual organs.
Development of the female secondary sex characters.
Control of the menstrual cycle.
Uses





Birth control pills.
Failure of ovarian development.
Menstrual disturbances.
Postmenopausal osteoporosis.
Prostate cancer.
Side Effects



Nausea, vomiting and diarrhea.
Sodium and water retention.
Inhibition of ovulation in large doses.
Steroidal Estrogenic Drugs
Estradiol:



Most active natural estrogen.
Very short duration of action.
Mainly used for local effect on the uterus.
Ethinyl estradiol:

15- 20 more potent than estradiol orally.
OH
C CH
OH
HO
HO
17-estradiol
Ethinyl estradiol
(Stertoidal Semisynthetic estrogen)
Nonsteroidal Estrogens
Diethylstilbestrol:

The trans form is the active one.
Advantages:
As active as Estradiol.
 Longer duration of action.
 Orally active
 Cheap.

Disadvantages:

OH
HO
Increase the risk of uterine cancer.
Uses:

Treatment of prostate cancer.
Progestins

Progesterone in the major natural progestin.
Secretion: By the ovary mainly the corpus luteum during the
second half of the menstrual cycle.
Physiological Effects:


Development of the endometrium.
Development of the mammary gland during pregnancy.
Structure Activity Relation-ships:
Steroidal nucleus essential for
activity.
 Removal of the 19 CH3 increase
activity.
 Unsaturation of ring B or C
increase the activity.
 Have some androgenic activity.
 Removal of the keto function
remove androgenic activity.

O
O
Progestrogenic Drugs
Lynestrenol:

Semisynthetic progestin with pure progestrogenic
activity.
OH
O
C
O
Progesterone
(Natural)
Lynesrenol
(Synthetic)
CH
Uses:





Contraceptive pills.
Uterine bleeding.
Prevention of abortion.
Amenorrhea, dysmenorrhea, endometriosis.
Renal and breast carcinoma.
Side Effects:
Nausea, vomiting, irregular bleeding, edema, weight
gain.
Female Oral Contraceptive
Sequential Preparations:
 Estrogens for 16 days then Estrogen and
Progesterone for 5- 6 days.
 98- 99% successful.
Combination Preparation:
 Estrogens and Progesterone from the beginning to
the end in small doses.
 99- 100% successful.
Mechanism:
The above two types inhibit both FSH and LH so
prevent ovulation.
Female Oral Contraceptive (Cont.)
Minipills:
 Small doses of Progesterone from the beginning to
the end.
 97- 98% successful.
Mechanism:
 Alter the structure of the Endometrium.
 Increase consistency of the cervical mucus.
Male Sex Hormones
(Androgens)

Natural Androgens:
OH
O
OH
O
H
Testosterone
(Natural)
Dihydrotestosterone
(Natural)
Physiological Effects


Development of the male sexual organs and male
secondary sex characters.
Anabolic effect.
Uses
 Replacement therapy in cases of hypogonadism.
 Anabolic effect.



Side Effects
Sodium and water retention leads to edema.
Masculinization of women.
Hepatic dysfunction.
Structure Activity Relation-ships:






Steroidal nucleus essential for activity.
The C-3 and C-17 oxygenation increase the activity.
Oxidation of C-17 to carbonyl eliminates activity.
C-17 esters prolonged the activity.
Trans A/B ring junction is essential for activity.
17 a-substitutions render compounds orally active.
OH
O
Androgenic Drugs
OH
17 a-methyltestosterone:



CH3
Orally active.
Prolonged action.
Androgenic and anabolic effects.
O
17a-Methyltestosterone
(Semisythetic)
Synthetic Anabolic Steroids:
Norethandrolone
Orally active.
 Anabolic effects.
 C-10 CH3 group removed to
eliminate androgenic effect.
OH
C2H5

O
Norethandrolone
(Sythetic-Pure anabolic)
Adrenal Gland
Adrenal cortex secretes:
- Mineralocorticoids (mainly aldosterone)
- Glucocorticoids (mainly cortisol)
Adrenal medulla secretes:
- Epinephrine and lesser amounts of norepinephrine.
Steroidal Hormones
(Adrenocorticosteroids, Adrenocorticoids,
Corticosteroids, Corticoids)
Secretion:

Adrenal cortex of the adrenal gland.
Regulation:


Stimulation: ACTH.
Inhibition: Feed back Mechanism.
Classification of corticosteroids
Corticosteroids
Glucocorticoids
Mineralocorticois
Regulate carbohydrates, lipids
and proteins metabolism
Control electrolytes and water
balance
e.g. Hydrocortisone
e.g. Aldosterone.
Structure-Activity Relationship
Halogen & halomethylene greatly increase Topical antiinflammatory activity
Essential for activity
a-F increase all activities if no OH at C-17
a-F with 16aadihydroxy--inactive compounds
21
HO
O
Essential for antiinflammatory activity
& carbohydrate regulatory activity
18
HO
12
17
13
11
1, 2 Double bond improve carbohydrate
metabolism to Na+ retention
19
C
9
D
14
OH
Essential for antiinflammatory
activity
CH3 or OH
16
eleminate
Na+ retention activity
1
a-CH3 increase
glucocorticoid activity
10
2
A
O
Essential for activity
B
5
3
6
9a-Fluoro increase all activities
F Br Cl
4
a-CH3 in Cortisol increase all activities
a-CH3 in Prednisolone increase antiinflammatory activity
&Decrease Na+ retaining activity
Ether &
esters
increase
antiinflammat
ory &
glucocorticoid
activities
Physiological Functions and Pharmacological Effects
of corticosteroids :

Carbohydrates and Proteins Metabolism:





Lipids Metabolism:



Stimulate glucose formation in the brain.
Decrease peripheral utilization of glucose.
Promote storage of glucose in the liver.
Promote gluconeogenesis.
Redistribution of body fat (Buffalo hump, Moon face).
Enhance lipolyses of Triglycerides.
Electrolyte and Water balance:


Enhance reabsorption of sodium and water into plasma.
Increase urinary excretion of potassium.

Blood Picture:



Anti-inflammatory effects:


Increase hemoglobin and Red blood cells.
Decrease white blood cells.
Suppress inflammations regardless to their cause.
Immunosuppressive Effects:

Decrease immunity as a result of decrease the WBC’s.
Disease States (abnormalities of adrenal cortex function):
Addison’s disease:

Rare syndrome 1/100,000 due to Hypoadrenalism.
Causes:

Atrophy of adrenal gland.

Tuberculoses (result of infectious disease).

Low level of ACTH.
Symptoms:
Weakness, fatigue, depression and irritability.
 Anemia and low blood pressure.
 Loss of sodium and dehydration.
 Low blood sugar.
 Excess pigmentation on skin.
 Nausea and vomiting.

Cushing’s disease:

Rare syndrome 2- 5/Million due to Hyperadrenalism.
Causes:
Tumor of the Adrenal Cortex.
 Tumor of the Pituitary gland.

Symptoms:
Alteration of fat distribution.
 Hypertension.
 Osteoporosis.
 Growth retardation.
 Decrease Immunity.

Conn’s syndrom:
Causes:

Conn's syndrome is a disease of the adrenal glands involving
excess production of aldosterone (hyperaldosteronism).
Symptoms:
Hypertension.
 Alkalosis.
 Polyuria.
 Edema.

Adrenocorticoid Drugs
Systemic Corticosteroids:
* They can be administered by IV, IM, oral, topical or by inhalation.
* They can be short, intermediate or long-acting.
Cortisone and Cortisone acetate:
Can be given orally or by IM injection.
 Acetate has longer duration of action.
 Drug of choice in replacement therapy.

HO
HO
O
HO
O
O
OH
O
OH
O
Cortisol
Hydrocortisone
Cortisone
Cortisone acetate

Fludrocortisone:




9a-fluorocortisone.
10 times more active than cortisone as antiinflammatory.
300- 800 times more active as mineralocorticoids.
Prednisone and Prednisolone:


They are Δ1 corticoids.
3, 4 times more active than cortisone and hydrocortisone.
HO
HO
O
HO
O
O
OH
O
O
Prednisolone
Prednisone
OH

Dexamethasone:
9a-fluoro, 16a-methylprednisolone.
 5- 7 times more active than prednisolone.


Betamethasone:
9a-fluoro, 16-methylprednisolone.
 Slightly more active than Dexamethasone.

HO
HO
O
O
HO
HO
OH
OH
CH3
CH3
F
F
O
O
Dexamethasone
Betamethasone
Clinical uses





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

Hypoadrenalism.
Rumatic diseases.
Renal diseases.
Collagen diseases.
Ocular diseases.
Skin diseases.
GIT inflammation.
Liver diseases.
Side effects
Due to Prolonged use:
Fluid and electrolyte disturbances, edema and
hypertension.
 Hyperglycemia and glucosuria.
 Peptic ulcer.
 Increase susceptibility to infections.
 Growth arrest

 Osteoporoses
Withdrawal Symptoms:

Rapid withdrawal after prolonged use leads to sever
hypoadrenalism.
Hormones of posterior lobe of
Pituitary gland
The posterior lobe is the source of 2 hormones:
 Vasopressin (ADH)
 Oxytocin (OT)
Antidiuretic Hormone (ADH)
Function:
- ADH is to conserve body water by reducing the loss of water
in urine.
- ADH binds to receptors on cells in the collecting ducts of the
kidney and promotes reabsorption of water back into the
circulation.
Diabetis insipidus DI
(Hyposecretion of ADH)
This condition can arise from either of two situations:
Hypothalamic diabetes insipidus:
■ Results from a deficiency in secretion of ADH from
the posterior pituitary.
■ Causes of this disease include head trauma and infections or
tumors involving the hypothalamus.
Nephrogenic diabetes insipidus:
■ occurs when the kidney is unable to respond to ADH.
■ Most commonly, this results from some type of renal disease.
Sign & symptoms: polyuria (10-12 L/ day)
Treatment: Synthetic vasopressin injection (Pitressin)
Oxytocin
Function in female:
-Stimulation of milk ejection
- Stimulation of uterine smooth muscle contraction.
Definition
A food supplement, also known as dietary supplement or
nutritional supplement, is a preparation intended to
provide nutrients that are missing or are not consumed in
sufficient quantity in a person's diet.
 Marketed as pills, tablets, capsules, liquids in measured doses.
Essential organic nutrients: that promote energy for living
organisms requiring them are:
- Amino acids (the precursors of protein)
- Fatty acids
- Carbohydrates.
- Purine and pyrimidine and their derivatives (precursors
of nucleic acids).
- Vitamins.
Essential inorganic nutrients that promote the growth and
maintenance of living organisms such as:
boron, calcium, iodine, iron, magnesium,
potassium, selenium and zinc

All nutrients required for human life work interdependently
in order to metabolize and facilitate optimal functioning.
E.g.: intake of calcium requires a complementary amount of
magnesium so the calcium will be absorbed properly.
An excess of calcium may be responsible for a magnesium
deficiency.
When You May Need a Dietary Supplement





You eat a very low-calorie diet
You eat an all-plant diet (vegan)
You are in a certain stage of the life cycle (e.g., a pregnant,
breastfeeding)
Your doctor may prescribe a supplement for you if:
 You have a disease, infection, or injury or recently had
surgery
 You have a nutritional deficiency
 You are taking medications that interfere with your body’s
use of specific nutrients
Dietary supplement would include:
■ Vitamins (e.g.: Vitamin B6, Niacin,Vitamin C)
■ Minerals (e.g.: Calcium and Iron)
■ Amino acid (e.g.: Tyrosine, Creatine,
L-tryptophan, Phenylalanine)
■ Herbals

Food and Drug Administration (FDA) advises caution with
amino acid supplements.
E.g.: L-tryptophan and phenylalanine in dietary supplement
caused potential risks for:







Pregnant women.
Infants.
Children.
Adolescents.
Elderly.
Individuals with inherited disorders of amino acid metabolism.
Individuals with certain diseases.

Eosinophilia-myelgia syndrome (EMS) was associated with
the ingestion of L-tryptophan in a dietary supplement.

EMS is a systemic connective tissue disease characterized by:
- Severe muscle pain
- Increase in white blood cells
- Certain skin and neuromuscular manifestations.
 People with phenylketonuria (PKU), a rare genetic condition,
when ingest too much phenylalanine, serious problems could
occur, especially brain and mental problems in children.
Herbs

Combining herbals with medicines can result in an adverse reaction
where "double-dosing" can occur or a worsening of symptoms in
those with a chronic medical condition.
Some of the fastest growing herbal categories include the following:
 Herbals that increase circulation (Ginko biloba)
 Herbals used for calmative effect (Kava kava, Valerian,
Chamomile)
 Herbals to lessen a cold flu symptoms and boost immunity
(Echinacea, Goldenseal)
 Herbs for mild depression (St. John's Wort ).
 Herbs for inflammation (Curcuma domestica).
 Herbs for lowering cholesterol (Allium sativum).
 Herbs to treat hypertension (Valariana officinalis, Panax
ginseng)
Be careful when using Herbal Supplements:
 Herbals can interact with drugs used for anesthesia (all herbals be
discontinued 2-3 weeks prior to a scheduled surgery).
 Stop all herbals if pregnant or breast-feeding.
 Many herbals can interact with the anticoagulant:
- Avoid taking supplements of garlic, ginko biloba, ginger,
while taking the blood thinner Coumadin® as these
herbs can further prolong clotting times.
 Don't give herbal remedies to children without first checking with
the child's pediatrician.
 Don't take herbal products containing ephedra. Many deaths have
been associated with its use.

Many drugs interact with St. John's Wort, prompting the FDA to
issue a health advisory:
St. John's Wort can cause some drugs to be eliminated from the body
too quickly, making them less effective such as oral contraceptives,
anti-cancer agents, heart medications and drugs that fight HIV.
Possible Side Effects of Supplement Use








Dehydration
Nervousness and Dizziness
Changes in Blood Pressure and Heart Rate
Heart Attack
Seizures
Psychosis
Death
Interaction with medications
Supplements to Avoid

Steroids and Steroid-Enhancers
 Linked to liver toxicity and increased risk of heart
attack.

Kava Kava
 Linked to liver damage
 Banned in European countries and Canada

St Johns Wort
 Interferes with a huge number of medications
Dietary Supplements D/S
DSHEA (Dietary Supplement Health Education Act)
 DSHEA defines a dietary supplement as any product that contains a vitamin,
mineral, herb, or amino acid and that
is intended as a supplement to the normal diet.
 Distinguished from Drugs:
 Drug must undergo FDA approval after clinical studies to
determine effectiveness and safety D/S = no pre-market testing


DSHEA authorized to provide accurate information to consumers and
the label must include:
 Name of each ingredient
 Quantity of each ingredient
 Total weight of all ingredient if a blend
 Identity of part of plant derived from
 Term “Dietary Supplement”
Statements may be included on the label that give the manufacturers
description of the role of the D/S
 Not authorized by FDA
Food coloring is any substance that is added to food or drink
to change its color.
Purpose of food coloring
Offsetting color loss due to light, air, extremes of temp.,
moisture, and storage conditions.
- Enhancing naturally occurring colors.
- Decorative purposes.
Natural food dyes
• Caramel coloring (E150), made from caramelized sugar,
used in cola products and also in cosmetics.
Annatto (E160b), a reddish-orange dye
made from the seed of the Achiote.
• Turmeric (curcuminoids, E100)
• Saffron (carotenoids, E160a)
• Paprika (E160c)
Side effects of coloring agents
• A great deal of research finds definite connections between
behavioral problems and hyperactivity in children.
• Other effects on health from food dyes are allergies, headache,
asthma, fatigue, nausea, concentration problems, agitation and
nervousness.