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Progesterone

Also known as: Corpus Luteum Hormone; Luteohormone; Pregnancy Hormone; Progestational Hormone

Description

Progesterone is a type of female Sexual Steroid Hormone secreted by the Ovaries, Placenta and (in small amounts) by the Adrenal Cortex and (in males) the Testes.

View Progesterone's Biochemical Pathway

Biological Function and Therapeutic Applications of Progesterone

Cardiovascular System
Progesterone inhibits the excessive proliferation of the Smooth Muscle of the Endothelium of Blood Vessels (excessive proliferation of the Smooth Muscle of the Endothelium of Blood Vessels can lead to Atherosclerosis). research
Progesterone helps to prevent many types of Cardiovascular Diseases (due to its ability to minimize risk factors for Cardiovascular Diseases such as elevated LDL Cholesterol, lowered HDL Cholesterol and elevated Triglycerides levels). research
Progesterone helps to prevent Heart Attack. research
Progesterone helps to prevent Hypertension (by facilitating the excretion of excessive Sodium from the body).

Hair
Supplemental, natural Progesterone can protect against the Hair Loss that affects some post-menopausal women. research
Supplemental, natural Progesterone often alleviates Hirsutism:
 
-Anecdotal reports from menopausal and menstruating women indicate that facial and body Hair decreases or disappears after 3 - 6 months of twice daily topical use of Progesterone cream.
Topical application of Progesterone (2% - 5% cream) retards further Hair Loss and may stimulate some regrowth of Hair in men afflicted with Male Pattern Baldness. research

Immune System
Optimal endogenous Progesterone levels appear to assist the prevention of all forms of Cancer (in women): research
 
-Optimal endogenous Progesterone levels help to prevent the development of Breast Cancer. research
-Supplemental, exogenous natural Progesterone helps to prevent Endometrial Cancer in postmenopausal females (by counteracting Estrogens-dominance that is implicated in Endometrial Cancer).

Metabolism
Progesterone facilitates the utilization of Adipose Tissue in Energy production.
Progesterone lowers total serum Cholesterol levels:
 
-Progesterone increases HDL Cholesterol levels. research
-Progesterone lowers elevated LDL Cholesterol levels. research
Progesterone lowers elevated serum Triglycerides levels. research

Musculoskeletal System
Exogenous, natural Progesterone (applied topically for at least five consecutive days) may reduce Inflammation and Pain in the Joints and improve the flexibility of damaged Joints (according to anecdotal reports).
Supplemental, exogenous, natural Progesterone stimulates the production of Osteoblasts and stimulates Osteoblast-mediated Bone formation (Osteoblasts contain receptors for Progesterone). research
Supplemental, exogenous, natural Progesterone (especially in post-menopausal females) prevents and REVERSES Osteoporosis (by stimulating Osteoblast activity): research
 
-Progesterone deficiency is a major cause of Osteoporosis and clinical studies have shown that supplemental Progesterone increases bone mass density (BMD) by 7% after 1 year of supplementation, by 12% after 2 years, and by 15% after 3 years. Women administered supplemental Progesterone up to the age of 80 following Menopause exhibit strong Bones without evidence of Bone loss while continuing to use natural Progesterone.

Nervous System
Progesterone alleviates and helps to prevent some forms of Depression:
 
-The female body's decline in Progesterone production is involved in Postpartum Depression and supplemental, natural Progesterone may alleviate Postpartum Depression.
Irritability can occur as a result of abnormally low Progesterone levels.
Progesterone facilitates the formation and maintenance of Myelin Sheaths. research
Progesterone helps to restore normal Sleep cycles.
Children whose mothers used Natural Progesterone during their Pregnancy exhibit superior Verbal Fluency.

Sexual System - Female
Natural, exogenous Progesterone (cream applied topically) alleviates many cases of Amenorrhea (by restoring the body’s Progesterone:Estrogens ratio).
Natural (exogenous, supplemental) Progesterone alleviates the symptoms of Endometriosis and appears to slowly reverse the proliferation of Endometrial Tissue that underlies Endometriosis:
 
-It is recommended that females afflicted with Endometriosis use Progesterone from day 10 to day 26 of their monthly menstrual cycle, increasing the dosage until the pain in their pelvic area decreases.
Exogenous Progesterone (applied topically to the Breasts) alleviates Fibrocystic Breast Disease (according to the observations of many physicians).
Many cases of Luteal Phase Defect occur as a result of abnormally low production of Progesterone during the Luteal Phase of the Menstrual Cycle.
Optimal endogenous Progesterone levels help to prevent Mammary Dysplasia (premalignant, abnormal development of Breast tissue).
Chronic Menorrhagia (excessive or prolonged bleeding during Menstruation) is often caused by sub-optimal Progesterone levels (and supplemental, exogenous, natural Progesterone cream applied topically is often utilized to alleviate Menorrhagia). research
Progesterone helps to prevent Miscarriage:
 
-Progesterone prevents the premature shedding of the supportive secretory Endometrium during Pregnancy.
-Any premature fall in Progesterone levels during Pregnancy or blockage of its Receptors sites within the body will cause Miscarriage.
-Exogenous, supplemental Progesterone is sometimes administered to females in danger of Miscarriage during Pregnancy.
Low serum Progesterone levels result in the PMT-A (Anxiety) form of Pre-Menstrual Syndrome (PMS):
 
-PMT-A most commonly occurs as a result of Estrogens dominance, secondary to relative Progesterone deficiency.
Progesterone prepares the inner lining (Endometrium) of the Uterus for Pregnancy:
 
-If fertilization occurs, it maintains the Uterus throughout Pregnancy and prevents the further release of eggs from the Ovaries.
Progesterone increases female Sexual Desire.
Progesterone (Progesterone cream applied intravaginally) alleviates many cases of Vaginal Atrophy. research
Supplemental, natural, exogenous Progesterone (cream applied topically) alleviates Vaginitis.

Skin
Progesterone (as a component of some Cosmaceutical Skin Moisturizers) alleviates Dry Skin (by facilitating the retention of Water in the Skin).

Progesterone Enhances the Production/Function of these Substances

Hormones
It is claimed that Progesterone (cream applied topically to the soft parts of the Skin - male scrotum and female breasts) can significantly increase the body's Dehydroepiandrosterone (DHEA) production.
Progesterone protects the body against the potentially toxic effects of excessive quantities of unopposed (exogenous or endogenous) Estrogens.
Progesterone increases Insulin levels and increases the Insulin response to dietary Glucose.

Minerals
Progesterone facilitates the excretion of excessive Sodium from the body (due to Progesterone competing with Aldosterone for occupancy of the Kidneys):
 
-Note that synthetic Progestins have the opposite effect of causing Sodium retention.

Pharmaceutical Drugs
Supplemental Progesterone counteracts many of the potentially toxic effects of Synthetic Estrogens.

Smart Drugs
Progesterone increases the effectiveness of Pyrrolidone Derivative Nootropics:
 
-Aniracetam
-Oxiracetam
-Piracetam
-Pramiracetam

These Substances Enhance the Function of Progesterone

Hormones
Chorionic Gonadotrophic Hormone (CGH) stimulates the Corpus Luteum of the female Ovaries to produce Progesterone.
Luteinising Hormone (LH) stimulates the Corpus Luteum during the Luteal Phase of the Menstrual Cycle to produce Progesterone.
Prolactin stimulates the production of Progesterone within the Ovaries.

Proteins
Cortisol Binding Globulin (CBG) facilitates the transport of Progesterone around the body via the Plasma within the Bloodstream:
 
-CBG binds to (90-98% of) Progesterone, transports it via the bloodstream and when in close proximity to a Cell, releases it for transport through the Cell Membrane into the Cytoplasm of Cells (where, if it then encounters an accessible Progesterone Receptor it migrates into the Cell's Nucleus).

Saponins
Diosgenin (found in Mexican Wild Yam) stimulates the production of endogenous Progesterone.
Sarsapogenin (found in Sarsaparilla) stimulates the production of endogenous Progesterone.

Vitamins
Vitamin B6 helps to restore normal production of Progesterone in females afflicted with the PMT-A (Anxiety) form of Pre-Menstrual Tension (PMT).
Vitamin E increases Progesterone levels where endogenous Progesterone levels are deficient.

These Herbs Facilitate the Production of Progesterone

Chaste Berry may mimic the ability of Luteinising Hormone (LH) to stimulate the production of Progesterone in the Corpus Luteum during the Luteal Phase of the Menstrual Cycle. research
Mexican Wild Yam and other Yams contains a Steroidal Saponin (named Diosgenin) that mimics the actions of Progesterone and which MAY function as a precursor for the manufacture of endogenous, natural Progesterone after it has been ingested.
Sarsaparilla contains a Steroidal Saponin (named Sarsapogenin) that mimics the actions of Progesterone and which MAY function as a precursor for the manufacture of endogenous, natural Progesterone after it has been ingested.

Endogenous Production of Progesterone

 Daily Progesterone Production
 OvariesPlacentaTestesAdrenal Cortex
Females - Pre-Ovulation:2-3 mg Not Applicable 
Females - Ovulating:22 mg Not Applicable 
Females - 1 Week after Ovulation:30 mg Not Applicable 
Females - During 3rd Trimester of Pregnancy-300-400 mgNot Applicable 
Males:Not ApplicableNot Applicable0.25 - 2.5 mg0.25 - 2.5 mg

These Substances Interfere with Progesterone

Hormones
Oxytocin facilitates luteolysis, resulting in cessation of Progesterone synthesis and subsequently, Menstruation.
 
-Oxytocin is not regarded as toxic as the temporary cessation of Progesterone production is a normal aspect of the female Menstrual Cycle.

Pharmaceutical Drugs
Progesterone Antagonists (e.g. Mifepristone) interfere with Progesterone by competing with Progesterone for occupancy of Progesterone Receptors.

These Factors Decrease the body's Production of Progesterone

Sexual System - Female
The female body's endogenous production of Progesterone falls to zero (or very close to zero) during and for some time prior to Menopause:
 
-In fact serum levels of Progesterone in menopausal females are lower than that of a male's.
-Supplemental, exogenous Natural Progesterone can alleviate the discomfort experienced by many females prior to, during and immediately following Menopause.

Toxic Effects of Excessive Progesterone

Sexual System - Female
Elevated serum Progesterone levels during the midluteal phase are associated with the PMT-D (Depression) form of Pre-Menstrual Syndrome (PMS) - although low serum Progesterone is associated with another type (PMS-A) form of PMS.

Dosage Recommendations

Oral Progesterone
The most commonly prescribed dosage of oral Progesterone is 100 mg per day for women with a Uterus and 50 mg per day for women who have had a Hysterectomy (the exact dosage should be determined by a physician).

Topical Progesterone Cream
The usual dosage of topically-applied natural Progesterone cream is 20 - 40 mg per day. For a natural Progesterone cream that contains 1.763% Progesterone this would equate to approximately ¼ to ½ teaspoon of cream per day.

Myths Dispelled

"True" (i.e. natural, endogenously manufactured) Progesterone is often classified as a type of Progestin - natural Progesterone has a different (although similar) chemical structure to Progestins and does NOT cause side-effects to the same extent as synthetic Progestins.

Bioavailability

Endogenous Progesterone
90 - 98% of the body's Progesterone is bound to Cortisol Binding Globulin (CBG) for transportation around the bloodstream. Approximately 2-10% of the body's Progesterone travels through the bloodstream in its "unbound" state.
Eventually Progesterone is transported to the Liver where it is inactivated and metabolized:
 
-In the Liver, Progesterone is metabolized (by means of reduction, i.e. hydrogenation) to three groups of inactive substances:Pregnanedione, Pregnanalones and Pregnanediol.
-These inactive metabolites are then bonded with Glucuronic Acid and excreted as water-soluble Glucuronides via (primarily) the Bile and (secondarily) the Urine.

Injection
When dissolved in vegetable oil and administered by injection Progesterone is absorbed rapidly and is thoroughly effective.
When injected intramuscularly, Progesterone in quantities above 100 mg is locally irritating.

Oral Bioavailability
In general, Progesterone (natural Progesterone) is poorly absorbed when administered orally.
Supplemental, oral Progesterone is absorbed more efficiently when it is micronized (i.e. as an ultra-fine powder) rather than ingested as standard, crystalline powder (which is poorly absorbed):
 
-If supplemented orally, natural Progesterone requires a daily dosage of approximately 5 - 8 times the dosage utilized for topically (transdermally) applied Progesterone in order to equal the effectiveness of topically applied Progesterone.

Topical Bioavailability
Exogenous Progesterone is absorbed extremely efficiently through the Skin (in the form of a topically applied cream):
 
-Topically administered Progesterone is absorbed into the Subcutaneous Tissue layer of the Skin where it is then slowly released into the bloodstream.
-Less Progesterone is removed from circulation by the Liver when Progesterone is administered in the form of topically applied cream - oral supplements are largely broken down within the Liver before their effects have a chance to operate.

Transrectally
Supplemental, Natural Progesterone is well-absorbed when administered transrectally.

Transvaginally
Supplemental, Natural Progesterone is well-absorbed when administered transvaginally.

Commercial Availability of Progesterone

Topical Progesterone Products
Natural Progesterone is available over-the-counter (OTC) from most health food stores and mail order supplement companies in the USA (but not in other countries) in the form of a topical cream. It is often (but not always) labeled as “Progest”. Most health food store brands of natural Progesterone cream contain a total of 25 mg of Progesterone per ¼ teaspoon. Natural Progesterone creams are usually sold in the form of 2 ounce (56.7 gram) jars.
For women who require a higher level of natural Progesterone than 25 mg per ¼ teaspoon, compounding Pharmacies are able to prepare higher potency natural Progesterone creams.
Some brands of natural Progesterone creams are combined with Liposomes in order to enhance their topical bioavailability.
Some brands of natural Progesterone creams are combined with other Steroid Hormones (such as Dehydroepiandrosterone (DHEA) and/or Pregnenolone).

Wild Yam as a source of Progesterone?
The labeling on some topically-applied Mexican Wild Yam creams misleadingly implies that they contain natural Progesterone - consumers are advised to read the ingredients statement on such products and if the terms “natural Progesterone” or “USP Progesterone” are absent, then the product should not be regarded as a source of supplemental Progesterone.

Progestins
Many Progestins (i.e. analogues of Progesterone) are claimed to be or are marketed as Progesterone. As mentioned above, Progestins have a different chemical structure to natural Progesterone and do not provide the full spectrum of Natural Progesterone's biological activity and can cause numerous toxic side-effects. The primary reason for the development of Progestins as analogues of Progesterone was to allow pharmaceutical companies to hold patents on their chemical structure (which are unavailable in respect of true Progesterone - a natural substance).

Best Form?
The optimal form of Progesterone is Natural Progesterone - i.e. Progesterone with an identical chemical structure to that found within the body:
 
-Natural Progesterone is produced by chemically modifying Diosgenin to produce (theoretically synthetic, but an exact replica of) Natural Progesterone.

Legal Considerations
There are no legal restrictions in the USA on the provision of supplemental, natural Progesterone in topically-applied form (at a level of up to 25 mg of natural Progesterone per ¼ teaspoon of cream). In other countries, the procurement of natural Progesterone at any potency generally requires a prescription.

Chemical Data

Chemical Names
Pregn-4-ene-3,20-dione
4-pregnene-3,20-dione

Molecular Formula
C21H30O2

Related Topics

Contraceptive Pill
Cortisol Binding Globulin
Female Sexual System
Hydroxyprogesterone
Ovaries
Progestins
Progesterone Antagonists


Return Estrogens Dominance

Estrogens Dominance (also known as Unopposed Estrogens) is the term applied to excessive Estrogens relative to their natural “controllers” - in females Progesterone counteracts many of the potentially toxic effects of excessive Estrogens, whilst in males Testosterone performs this function. Estrogens Dominance can occur either as a result of excessive Estrogens production or as a result of insufficient production of its “controllers”.


Return Exogenous

Exogenous means that a given chemical or substance originates outside the body. In this program the term is applied particularly to substances introduced into the body that are derived from supplements or from the diet, as opposed to being manufactured by the body's own metabolic processes.



Return Endogenous

Endogenous means that a given chemical or substance is manufactured within the human body by the body's own metabolic processes, often relying on exogenous (i.e. chemicals introduced into the body via supplements or the diet) precursors.



Return Luteolysis

Luteolysis is the regression of the Corpus Luteum in the midluteal phase of the ovarian cycle, resulting in cessation of Progesterone synthesis and subsequently, Menstruation