Progesterone is a hormone produced by a woman’s ovaries during the middle, or luteal, phase of her menstrual cycle. Progesterone is also made in small amounts in other parts of the body such as the adrenal glands, and the nervous system. In women, progesterone has important effects on the brain, breast, uterus, ovaries and cervix. Adequate progesterone is necessary for normal menstrual cycles and pregnancy.

Progesterone may be called natural progesterone or bioidentical progesterone, to distinguish it from synthetic hormones, such as the progestins, found in birth control pills and some pharmaceutical hormone replacement therapy (HRT).

Progesterone has many important roles in a woman’s health. One of progesterone’s primary functions is to balance the effects of estrogen, the female hormone. When estrogen is out of balance with progesterone it can cause uncontrolled cell growth, which can lead to cancer, especially of the breast, ovaries and uterus. The presence of progesterone assures that cell growth stays in balance in the presence of estrogen.

When estrogen is not balanced by progesterone, this is known as estrogen dominance. This is a common form of hormone imbalance caused by a relative deficiency of progesterone. Estrogen dominance can lead to bloating, mood swings, irritability, weight gain and tender breasts. Estrogen and progesterone in balance with each other helps create overall hormone balance.

An ovulating woman typically makes an average of 30 mg per day of progesterone during the last two weeks of her menstrual cycle. Some women may ovulate, but then not produce a normal amount of progesterone, which is known as luteal phase deficiency. Some women may not ovulate at all during their menstrual cycle, causing a progesterone deficiency. Low progesterone or progesterone deficiency becomes more common as women age.

When women become pregnant, progesterone levels start to rise at the end of the first trimester, and by the third trimester the placenta is making around 300 mg of progesterone daily. OB/Gyns often use progesterone supplementation when pregnant women are at risk of preterm labor.

Progesterone is a calming hormone because it affects the GABA receptors in the brain. Perimenopausal women with insomnia often have a progesterone deficiency.

Symptoms of Progesterone Deficiency in Pre-menopausal Women

• Irregular periods
• Bloating
• Cramping
• Irritability
• Insomnia
• Headaches
• Restlessness
• Anxiety
• Breast tenderness
• Mood swings
• Weight gain

Symptoms of Progesterone Deficiency in Perimenopausal and Menopausal Women

• Mood swings
• Insomnia
• Headaches
• Restlessness
• Anxiety
• Depression
• Breast tenderness
• Weight gain
• Hot flashes
• Night sweats
• Vaginal dryness
• Thyroid deficiency symptoms
• Foggy thinking
• Fatigue

Progesterone and Hormone Imbalance in Menopause

As a woman ages, she produces less and less progesterone. When she reaches menopause, usually around the age of 50, she is making almost no natural progesterone, but continues to make some estrogen and some testosterone. For many women, this deficiency of progesterone can bring on the menopause symptoms listed above, that are the hallmarks of a menopausal hormone imbalance.

Research

Progesterone and the Risk of Preterm Birth among Women with a Short Cervix
Eduardo B. Fonseca, M.D., Ebru Celik, M.D., Mauro Parra, M.D., Mandeep Singh, M.D., and Kypros H. Nicolaides, M.D. for the Fetal Medicine Foundation Second Trimester Screening Group
N Engl J Med 2007; 357:462-469 August 2, 2007DOI: 10.1056/NEJMoa067815
http://www.nejm.org/doi/full/10.1056/NEJMoa067815

Journal: General Obstetrics and Gynecology Obstetrics Prophylactic administration of progesterone by vaginal suppository to reduce the incidence of spontaneous preterm birth in women at increased risk: A randomized placebo-controlled double-blind study Eduardo B. da Fonseca, MD
(Am J Obstet Gynecol 2003;188:419-24.)
http://www.ncbi.nlm.nih.gov/pubmed/12592250

Progesterone and Breast Cancer

Climacteric. 2012 Apr;15 Suppl 1:18-25. doi: 10.3109/13697137.2012.669584.
Micronized progesterone and its impact on the endometrium and breast vs. progestogens.
Gompel A.
http://www.ncbi.nlm.nih.gov/pubmed/22432812

Breast Cancer Res Treat. 2007 Jan;101(2):125-34.
Effects of estradiol with micronized progesterone or medroxyprogesterone acetate on risk markers for breast cancer in postmenopausal monkeys.
Wood CE1, Register TC, Lees CJ, Chen H, Kimrey S, Cline JM.
http://www.ncbi.nlm.nih.gov/pubmed/16841178

Progesterone and GABA Receptors

Prog Neurobiol. 2014 Feb;113:6-39. doi: 10.1016/j.pneurobio.2013.09.004. Epub 2013 Oct 27. Revisiting the roles of progesterone and allopregnanolone in the nervous system: resurgence of the progesterone receptors. Schumacher M1, Mattern C2, Ghoumari A3, Oudinet JP3, Liere P3, Labombarda F4, Sitruk-Ware R5, De Nicola AF4, Guennoun R3. http://www.ncbi.nlm.nih.gov/pubmed/24172649

Progesterone and Brain Injury

Brinton RD, Thompson RF et al, “Progesterone receptors: form and function in brain,” Front Neuroendocrinol 2008 May;29(2):313-39. Epub 2008 Feb 23.
http://www.ncbi.nlm.nih.gov/pubmed/18374402

Neuroscience. 2011 Sep 15;191:101-6. doi:
10.1016/j.neuroscience.2011.04.013. Epub 2011 Apr 14. Progesterone in the treatment of acute traumatic brain injury: a clinical perspective and update.
Stein DG.
http://www.ncbi.nlm.nih.gov/pubmed/21497181

Horm Behav. 2013 Feb;63(2):291-300. doi: 10.1016/j.yhbeh.2012.05.004. Epub 2012 May 14. A clinical/translational perspective: can a developmental hormone play a role in the treatment of traumatic brain injury?
Stein DG.
http://www.ncbi.nlm.nih.gov/pubmed/22626570

Progesterone and Sleep

Psychoneuroendocrinology. 2013 Nov;38(11):2618-27. doi: 10.1016/j.psyneuen.2013.06.005. Epub 2013 Jul 10.
Autonomic regulation across phases of the menstrual cycle and sleep stages in women with premenstrual syndrome and healthy controls.
de Zambotti M1, Nicholas CL, Colrain IM, Trinder JA, Baker FC.
http://www.ncbi.nlm.nih.gov/pubmed/23850226

Mini Rev Med Chem. 2012 Oct;12(11):1040-8. Steroid hormones and sleep regulation.
Terán-Pérez G1, Arana-Lechuga Y, Esqueda-León E, Santana-Miranda R, Rojas-Zamorano JÁ, Velázquez Moctezuma J.
http://www.ncbi.nlm.nih.gov/pubmed/23092405

Progesterone and PMS

Biol Psychol. 2012 Dec;91(3):376-82. doi: 10.1016/j.biopsycho.2012.08.001. Epub 2012 Aug 10. Higher luteal progesterone is associated with low levels of premenstrual aggressive behavior and fatigue. Ziomkiewicz A1, Pawlowski B, Ellison PT, Lipson SF, Thune I, Jasienska G. http://www.ncbi.nlm.nih.gov/pubmed/22906865

Progesterone and Breast Tenderness

Sitruk-Ware LR, Stenkers N, Mowezowicz, et al: Inadequate corpus luteal function in women with benign breast disease. J Clin Endocrinol Metab 1977; 44:771 http://www.ncbi.nlm.nih.gov/pubmed/849987

Progesterone and Perimenopause

Front Biosci (Schol Ed). 2011 Jan 1;3:474-86.
The endocrinology of perimenopause: need for a paradigm shift.
Prior JC1, Hitchcock CL.
http://www.ncbi.nlm.nih.gov/pubmed/21196391

Progesterone and Menopause

Gynecol Endocrinol. 2012 Oct;28 Suppl 2:7-11. Epub 2012 Aug 1.
Progesterone for hot flush and night sweat treatment--effectiveness for severe vasomotor symptoms and lack of withdrawal rebound.
Prior JC1, Hitchcock CL.
http://www.ncbi.nlm.nih.gov/pubmed/22849758

Int J Pharm Compd. 2014 Jan-Feb;18(1):70-7.
The effectiveness of sublingual and topical compounded bioidentical hormone replacement therapy in postmenopausal women: an observational cohort study. Ruiz AD, Daniels KR. http://www.ncbi.nlm.nih.gov/pubmed/24881343

Deionized Water, Caprylic/Capric Triglyceride, Simulgel 600, Isohexadecane, Polysorbate 80, Progesterone, Glycerin, Grapefruit Seed Extract, Lecithin, Alcohol, Glyceryl Monocaprylate, Glyceryl Monoundecylanate, Sodium Hydroxymethylglycinate, Potassium Sorbate, parfum, p-Anisic Acid, Tocopheryl Acetate