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Progesterone

Progesterone

While some complementary and alternative techniques have been studied scientifically, high-quality data regarding safety, effectiveness, and mechanism of action are limited or controversial for most therapies. Whenever possible, it is recommended that practitioners be licensed by a recognized professional organization that adheres to clearly published standards. In addition, before starting a new technique or engaging a practitioner, it is recommended that patients speak with their primary healthcare provider(s). Potential benefits, risks (including financial costs), and alternatives should be carefully considered. The below monograph is designed to provide historical background and an overview of clinically-oriented research, and neither advocates for or against the use of a particular therapy.

Related Terms

  • 17-Alpha-hydroxyprogesterone, 17-alpha-hydroxyprogesterone caproate (17P), 17-alpha-OHP-C, allopregnanolone, bioidentical hormone therapy (BHT), Colirest™, Crinone®, cyclic medroxyprogesterone acetate, Cycrin®, danazol, depot medroxyprogesterone acetate (DMPA), dienogest, Dioscorea mexicana, diosgenin, drospirenone, dydrogesterone, Esolut®, Hematrol™, hormone replacement therapy (HRT), hormone therapy, intramuscular progesterone, luteal phase support, medroxyprogesterone, medroxyprogesterone acetate (MPA), megestrol, micronized progesterone, micronized transvaginal progesterone, Nestorone®, nomegestrol acetate, norethisterone, oral micronized progesterone (MP), ORG-2154, P4, pregn-4-ene-3,20-dione, PremPro®, Pro-gest®, progestagen, progesterone receptor, progesterone vaginal cream, progesterone-only contraceptive pill (POCP), progestins, progestogen, Prontogest®, Provera®, steroid hormone, transdermal progesterone, transdermal progesterone cream, trimegestone, Utrogest®, Utrogestan®, vaginal progesterone, yams.
  • Note: This monograph focuses on progesterone and not other members of the progestogen family, such as synthetic progestogens or metabolites.

Background

  • Progesterone is a steroid hormone produced in the ovaries, placenta (during pregnancy), and adrenal glands, and it is involved in the female menstrual cycle, the maintenance of pregnancy, and embryogenesis (the formation and development of a baby).
  • Progesterone levels are relatively low before ovulation, rise after ovulation, and are elevated during the luteal phase, which is the phase of the menstrual cycle that starts at ovulation and ends the day before menstruation. Progesterone testing is done to help find causes of infertility, to determine ovulation, to assess the risk of miscarriage, to monitor the function of the ovaries and placenta during pregnancy, and to help diagnose problems of the adrenal glands and some types of cancer.
  • Estrogen, another hormone, and progesterone work together in the body. Estrogen and progesterone combinations are commonly used in hormone replacement therapy (HRT) in postmenopausal women.
  • Progesterone may benefit women with menorrhagia (abnormally heavy and prolonged menstrual bleeding) and may serve as a treatment for premature birth prevention. Progesterone is also often used as a conception aid.
  • Progesterone has been examined for its effects in a variety of conditions, including breast pain, cognitive performance, endometriosis (condition in which uterine tissue grows outside of the uterus), menopausal symptoms, pre-eclampsia, and premenstrual syndrome. However, strong evidence is currently lacking.

Scientific Evidence

Uses

These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.

C Alzheimer’s disease

The benefits of progesterone may be due to its inclusion with estrogen in typical hormone replacement therapy (HRT). The effects of progesterone alone for Alzheimer’s disease have not been determined. Further research is required.

C Birth control

Progesterone-only birth control pills are a common contraceptive method for breastfeeding mothers. However, very limited clinical evidence is available for this indication.

C Bone density improvement

Progesterone may play a role in bone health, which is particularly important for postmenopausal women undergoing HRT. However, its long-term effect is unknown. Further research is required before conclusions can be drawn.

C Breast pain (mastalgia)

Preliminary evidence suggests that topical progesterone may relieve breast pain. More well-designed trials are needed before a conclusion can be made.

C Cocaine dependence

Progesterone may decrease cocaine use and reduce the “high” associated with cocaine use. More evidence is needed before a conclusion can be made.

C Cognitive performance

Some studies suggest that progesterone may enhance cognitive performance. More well-designed trials are needed in this area.

C Drug addiction (benzodiazepines)

Limited research failed to find effects of progesterone on benzodiazepine dependence. More well-designed trials are needed before a conclusion can be made.

C Endometriosis

Progesterone may help relieve painful symptoms associated with endometriosis (condition in which uterine tissue grows outside of the uterus). More well-designed trials are needed.

C Fertility (conception aid)

Progesterone may improve egg implantation and pregnancy rates. Studies have compared different types of progesterone, the effects of progesterone with another hormone, or progesterone vs. no treatment. More studies are needed before conclusions can be drawn.

C Food cravings (prior to menstruation)

Limited research failed to find effects of progesterone on chocolate or sweets cravings before menstruation. More well-designed trials are needed in this area.

C High cholesterol

Limited studies suggest that progesterone combined with estrogen may lower cholesterol in menopausal women. However, the benefits of progesterone alone are not yet determined. More evidence is needed before a conclusion can be made.

C Infant mortality (preterm infants)

Progesterone combined with estrogen may improve the health outcome of preterm infants. However, the benefits of progesterone alone are not yet determined. More well-designed trials are needed before a conclusion can be made.

C Memory enhancement (in healthy people)

Limited research suggests that progesterone may impair memory function. More well-designed trials are needed before a conclusion can be made.

C Menopausal symptoms (hot flashes)

The benefits of progesterone on menopausal hot flashes are unclear. More well-designed trials are needed.

C Menopausal symptoms (oral)

Progesterone in combination with estrogen may exert beneficial effects on symptoms of the oral mucosa associated with menopause. More well-designed trials examining the effect of progesterone alone are needed in this area.

C Menopausal symptoms (sleep)

The benefits of progesterone on lack of sleep associated with menopause are unclear. More well-designed trials are needed.

C Menopause (quality of life)

The benefits of progesterone on quality of life during menopause are unclear. More well-designed trials are needed before a conclusion can be made.

C Menorrhagia (heavy menstrual bleeding)

Limited research suggests that progestogen use may decrease menstrual blood loss in women with menorrhagia. However, the effect of progesterone is unclear. Further research is required before firm conclusions can be drawn.

C Miscarriage (prevention)

Progesterone may protect against miscarriage. More well-designed trials are needed.

C Mood and cognition in post-menopausal women

The effects of progesterone use as part of hormone replacement therapy (HRT) on postmenopausal mood and cognition have been studied. More well-designed trials examining the effect of progesterone alone are needed in this area.

C Mood disorders

There is a lack of evidence to support progesterone use for mood disorders. More well-designed trials are needed before a conclusion can be made.

C Parkinson’s disease

Progestogen combined with estrogen may improve symptoms of Parkinson’s disease in women. However, the effects of progesterone alone are currently unknown. Further research is needed.

C Postpartum problems (psychiatric)

The benefits of progesterone for psychiatric postpartum problems have not yet been determined. More evidence is needed in this area.

C Pre-eclampsia

Limited research suggests that progesterone use may prevent pre-eclampsia (high blood pressure in pregnancy). More well-designed trials are needed.

C Premature birth prevention

Preliminary evidence suggests that treatment with progesterone and the natural progestogen 17alpha-hydroxyprogesterone caproate (17P) during pregnancy may prevent premature birth. However, further research is required.

C Premenstrual dysphoric disorder

There is a lack of evidence for progesterone use for premenstrual dysmorphic disorder. More well-designed trials are needed before a conclusion can be made.

C Premenstrual syndrome

There is conflicting evidence on the benefits of progesterone use for premenstrual syndrome. More studies are needed before a conclusion can be made.

C Psychosis (hormone-related)

There is a lack of scientific evidence to support progesterone use for hormone-related psychosis. More studies are needed before a conclusion can be made.

C Schizophrenia

There is a lack of scientific evidence to support progesterone use for schizophrenia. More studies are needed before a conclusion can be made.

C Sleep apnea

There is a lack of scientific evidence to support the use of progesterone for sleep apnea. More well-designed trials are needed before a conclusion can be made.

C Stress

There is a lack of scientific evidence to support the use of progesterone for stress. More well-designed trials are needed before a conclusion can be made.

C Supplementation in preterm and very low birthweight infants

Limited research suggests that supplementation of preterm infants with estradiol and progesterone can help maintain intrauterine concentrations of these hormones. More well-designed trials are needed before a conclusion can be made.

*Key to grades:

Tradition

The below uses are based on tradition or scientific theories. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious and should be evaluated by a qualified health care professional.

  • Anorexia nervosa, anxiety, bleeding, brain tumors (with hormonal regulation), epilepsy, gastrointestinal conditions (stomach bleeding), general health maintenance, growth (infant development), heart conditions, high blood pressure (postmenopausal), hot flashes (following castration due to prostate cancer in men), libido (sex drive), migraine, mood (general), psychological conditions (postpartum mania), psychological disorders (related to sexual identity issues), psychosis (general), respiration, seizures, stroke, traumatic brain injury, uterine cancer (endometrial stromal sarcoma), vascular disorders (problems with blood vessels).

Dosing

The below doses are based on scientific research, publications, traditional use, or expert opinion. Many herbs and supplements have not been thoroughly tested, and safety and effectiveness may not be proven. Brands may be made differently, with variable ingredients, even within the same brand. The below doses may not apply to all products. You should read product labels, and discuss doses with a qualified healthcare provider before starting therapy.

Adults (18 years and older)

  • To treat cocaine dependence, 100-300 milligrams of progesterone has been taken by mouth twice daily for nine weeks.
  • To improve cognitive performance, five grams of progesterone has been taken by mouth before the 16th week of pregnancy for more than eight weeks. Additionally, in menopausal women, 25-100 milligrams of intramuscular progesterone at weekly intervals has been used.
  • To treat drug addiction, 1,983 milligrams of progesterone, in combination with benzodiazepine, has been taken by mouth daily for seven weeks, with the benzodiazepine being reduced 25% weekly after the third week. Progesterone was then continued for four weeks before being discontinued.
  • To enhance fertility, 300-800 milligrams of progesterone has been taken by mouth daily within 24 hours of embryo transfer and continued 30 days. Vaginal gel containing 90-600 milligrams of progesterone has been used from the day before embryo transfer for two weeks. Intramuscular progesterone (50-100 milligrams daily) has been used for up to two weeks, as well as 12.5 milligrams of intramuscular progesterone four times daily after a dose of human chorionic gonadotropin (hCG).
  • To reduce food cravings before menstruation, 1,200 milligrams of progesterone has been taken by mouth four times daily from the third week of the menstrual cycle to the second day after menstruation onset.
  • To improve quality of life during menopause, 200 milligrams of natural micronized progesterone has been taken by mouth daily from the 12th through 25th days of the menstrual cycle for nine months.
  • To improve sleep during menopause, 300 milligrams of micronized progesterone has been taken by mouth every evening for 21 days, followed by a washout period of two weeks and a second treatment interval of 21 days.
  • To reduce heavy menstrual bleeding, 300 milligrams of progesterone has been taken by mouth in three divided doses daily for six months. A coil releasing 65 micrograms of progesterone daily has been used.
  • To treat premenstrual syndrome (PMS), 300 milligrams of progesterone has been taken by mouth daily for 10 days prior to menstruation. A gel containing 400 milligrams of progesterone has been inserted into the vagina or rectum twice daily, beginning 14 days before menstruation onset, for four cycles. Vaginal suppositories containing 200-400 milligrams of progesterone twice daily have been used for up to two months. Rectal suppositories containing 200 milligrams of progesterone have been used twice daily from midcycle to menstruation onset for two successive cycles.
  • To improve bone density, 30 grams of topical progesterone has been applied every three weeks, followed by a one-week break.
  • To reduce breast pain, four grams of vaginal cream containing 2.5% natural progesterone has been used for six menstrual cycles from the 19th to the 25th day of the cycle.
  • To prevent miscarriage, vaginal progesterone (Crinone 8%) has been used daily for five days from the diagnosis of threatened abortion. Additionally, 200 milligrams of vaginal progesterone has been used three times daily two weeks after embryo transfer.
  • To treat postpartum problems, rectal suppositories containing 200 milligrams of progesterone have been used twice daily from midcycle to menstruation onset for two menstrual cycles.
  • To prevent premature birth, vaginal suppositories containing 100-200 milligrams of progesterone have been used daily between 24 and 34 weeks of pregnancy. Vaginal suppositories containing 25 milligrams of progesterone given twice daily have also been used. A vaginal gel containing 400 milligrams of progesterone, applied daily until delivery, the 37th week of pregnancy, or development of preterm rupture of membranes, has also been used.

Children (under 18 years old)

  • There is no proven safe or effective dose for progesterone in children.

Safety

The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.

Allergies

  • Avoid in people with known allergy or sensitivity to progesterone.

Side Effects and Warnings

  • Progesterone is likely safe when used in prescribed doses for a prescribed length of time.
  • Progesterone may cause breathing problems, changes in heart rate, confusion, cough, depression, fatigue, headache, irregular menstruation, hyperemesis gravidarum (nausea and vomiting), vaginal pruritus (inflammation), vertigo, and vision problems.
  • Progesterone may increase the risk of breast and ovarian cancer, endometriosis (condition in which uterine tissue grows outside of the uterus), heart disorders (such as deep vein thrombosis, myocardial infarction (heart attack), pulmonary embolism, and stroke), dysmenorrhea (painful menstruation), and uterine fibroids.
  • Progesterone may cause low blood pressure. Caution is advised in people taking drugs or herbs and supplements that lower blood pressure.
  • Drowsiness or sedation may occur. Use caution if driving or operating heavy machinery or if taking sedatives.
  • Use cautiously in people with heart conditions or depression.
  • Use cautiously in people who are taking agents that may affect levels of serotonin, agents that may affect levels of dopamine, estrogen therapy, gonadotropin-releasing hormone, opioids, or paclitaxel.
  • Avoid in people with known allergy or sensitivity to progesterone.

Pregnancy and Breastfeeding

  • There is currently a lack of scientific evidence on the use of progesterone during pregnancy or breastfeeding.
  • A progesterone-releasing intrauterine device, which delivers approximately 65 micrograms of progesterone daily, may be safe for use during breastfeeding with a doctor’s approval.

Interactions

Most herbs and supplements have not been thoroughly tested for interactions with other herbs, supplements, drugs, or foods. The interactions listed below are based on reports in scientific publications, laboratory experiments, or traditional use. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy.

Interactions with Drugs

  • Progesterone may cause low blood pressure. Caution is advised in people taking drugs that lower blood pressure.
  • Progesterone may increase the amount of drowsiness caused by some drugs. Examples include benzodiazepines such as lorazepam (Ativan®) or diazepam (Valium®), barbiturates such as phenobarbital, narcotics such as codeine, some antidepressants, sedatives, and alcohol. Caution is advised while driving or operating machinery.
  • Progesterone may also interact with acetaminophen, agents used for sexual enhancement, agents that may affect dopamine levels, agents that may affect heart rate, agents that may affect gamma-aminobutyric acid (GABA) levels, agents that may affect gonadotropin-releasing hormone levels, agents that may affect serotonin levels, agents that may enhance fertility, agents that may enhance cognitive function (memory), agents that may treat heart disorders, anticancer agents, antidepressants, estrogens, hormonal agents, neurologic agents (agents that may affect the brain), opiates, and paclitaxel.

Interactions with Herbs and Dietary Supplements

  • Progesterone may cause low blood pressure. Caution is advised in people taking herbs or supplements that lower blood pressure.
  • Because progesterone contains estrogen-like chemicals, the effects of other agents believed to have estrogen-like properties may be altered.
  • Progesterone may increase the amount of drowsiness caused by some herbs or supplements such as sedatives.
  • Progesterone may also interact with adlay (seeds of the wild grass Job’s tears, Coix lachryma-jobi), anticancer herbs and supplements, antidepressants, fiber, flaxseed, herbs and supplements used for sexual enhancement, herbs and supplements that may act as opiates, herbs and supplements that may affect gamma-aminobutyric (GABA) levels, herbs and supplements that may affect dopamine levels, herbs and supplements that may affect serotonin levels, herbs and supplements that may affect heart rate, herbs and supplements that may enhance cognitive function, herbs and supplements that may enhance fertility, herbs and supplements that may treat heart disorders, hormonal herbs and supplements, neurologic herbs and supplements (agents that may affect the brain), and soy.

Author Information

  • This information is based on a systematic review of scientific literature edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

References

Natural Standard developed the above evidence-based information based on a thorough systematic review of the available scientific articles. For comprehensive information about alternative and complementary therapies on the professional level, go to www.naturalstandard.com. Selected references are listed below.

  1. Allen, W. M. Physiology of the corpus luteum, V: the preparation and some chemical properties of progestin, a hormone of the corpus luteum which produces progestational proliferation. 1930;
  2. Berlin FS, Bergey GK Money J. Periodic psychosis of puberty. Medical Aspects of Human Sexuality. 1985;19(1):194.
  3. Camacho-Arroyo, I., Pasapera, A. M., Perez-Palacios, G., et al. [Progesterone and its metabolites in central nervous system function]. Rev.Invest Clin. 1995;47(4):329-340. View Abstract
  4. Dzugan SA and Scipione A. Progesterone misconceptions. Life Extension. 2006;12(4):48-55.
  5. Herzog, A. G. Catamenial epilepsy: definition, prevalence pathophysiology and treatment. Seizure. 2008;17(2):151-159. View Abstract
  6. Huang, M. C., Wang, Y. B., and Chan, C. H. Estrogen-progesterone combination for treatment-refractory post-partum mania. Psychiatry Clin.Neurosci. 2008;62(1):126. View Abstract
  7. Kastner, P., Krust, A., Turcotte, B., et al. Two distinct estrogen-regulated promoters generate transcripts encoding the two functionally different human progesterone receptor forms A and B. EMBO J. 1990;9(5):1603-1614. View Abstract
  8. Khalil, R. A. Sex hormones as potential modulators of vascular function in hypertension. Hypertension 2005;46(2):249-254. View Abstract
  9. Marshall, J. K. and Hunt, R. H. Hormonal therapy for bleeding gastrointestinal mucosal vascular abnormalities: a promising alternative. Eur.J.Gastroenterol.Hepatol. 1997;9(5):521-525. View Abstract
  10. Martin A, Barus J Houdret JC. A case of transvestism: a psychological and phenomenological outline. Annales Médico-Psychologiques. 1967;2(3): 427-437.
  11. Park, D., Huang, T., and Frishman, W. H. Phytoestrogens as cardioprotective agents. Cardiol.Rev. 2005;13(1):13-17. View Abstract
  12. Schiffman, S. S., Sattely-Miller, E. A., Suggs, M. S., et al. The effect of pleasant odors and hormone status on mood of women at midlife. Brain Res.Bull. 1995;36(1):19-29. View Abstract
  13. Spetz, A. C., Zetterlund, E. L., Varenhorst, E., et al. Incidence and management of hot flashes in prostate cancer. J.Support.Oncol. 2003;1(4):263-70, 272. View Abstract
  14. Teja, J. S. Periodic psychosis of puberty. A longitudinal case study. J.Nerv.Ment.Dis. 1976;162(1):52-57. View Abstract
  15. Young, J. K. Estrogen and the etiology of anorexia nervosa. Neurosci.Biobehav.Rev. 1991;15(3):327-331. View Abstract

The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.

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