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Progesterone Glossary Hormone Replacement Therapy Hormones & Pharmacological Agents


2 years, 3 months ago

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Posted on Apr 13, 2022, 4 a.m.

Progesterone is essential for a long and healthy life. The body’s need for progesterone spans an entire lifetime, from being essential for conception to offering resilience and gentle aging.

In women, progesterone is secreted in the second half of the menstrual cycle from the released corpus luteum and, in much greater quantity, by the placenta during pregnancy. In both sexes, progesterone is also synthesized from cholesterol in the cortex of the adrenal gland, where it is a necessary precursor to produce other hormones.  

Progesterone is also produced by cells in the body’s nervous system in the Schwann cells which form a protective layer around nerves known as the myelin sheath. The nervous system depends on the myelin sheath for insulation and for neurotransmission speed. Progesterone promotes myelin repair in both the central and peripheral nervous systems. Progesterone is also produced independently by nervous system cells, in the brain, and even inside of cells (intracrinology).

Effects of Progesterone 

Although it is considered primarily a “reproductive hormone” associated with menstrual cycles and pregnancy, progesterone provides benefits to all cells in the body, including those in the brain, heart, nerves, skin, and bones.  

Research indicates that “maternal progesterone” is at least partially responsible for gender differences in the human brain. Male and female brains have significant structural and neurobiological differences, including the number of progesterone receptors, which affects sensitivity to progesterone.  

These differences may be related to why progesterone has been a successful treatment for reducing seizures in some women, and why women’s brains tend to heal more easily after an injury. Progesterone protects the brain against excitotoxins (substances that excite the brain cells to the point of death), including estrogen-induced “brain fog” and research is underway to understand progesterone’s potential for protection against Alzheimer’s disease.  

Progesterone Receptors 

Every hormone has specific receptors or “target cells” that are particularly receptive to that hormone’s signals. Progesterone’s target cells are abundant in the brain and scattered throughout the rest of the body, such as in blood vessels, skin, and bones, as well as in the lungs, nose, throat, and eyes.  

Hormone activity takes place when a molecule reaches the cell nucleus. Progesterone’s “message” for that cell nucleus depends on the type of cell. For example, when progesterone reaches a brain cell nucleus, it helps improve brain function; when it reaches a bone cell nucleus, it helps make new bone cells. The broad range of progesterone receptor sites helps explain why progesterone is so essential for overall health. This is especially true for brain health, cardiovascular health, and skin and bones.  

Progesterone provides protection against cardiovascular disease by lowering high blood pressure, reducing arterial spasms, and inhibiting cholesterol buildup. These protective benefits are unique to progesterone, not synthetic progestins. In fact, progestins increase the risk of coronary spasms and are associated with an increased risk for cardiovascular disease.  

Progesterone also offers protection against osteoporosis. Current research indicates that progesterone has (at least) a dual role in bone health: it stimulates osteoblast production, which results in new bone growth, and it interferes with glucocorticoids, which cause bone loss. Dr. John Lee’s research demonstrates that progesterone not only prevents osteoporosis but, more importantly, can reverse it so that bones regain their normal bone mineral density.  

Another significant benefit of progesterone is that it is anti-proliferative, meaning it may offer protection against some forms of cancer, such as breast cancer. Breast tissue is highly sensitive to hormones, especially estrogen, which encourages breast cells to proliferate. Progesterone provides a counterbalance to that proliferation. Dr. Lee reports that the protective benefits of progesterone are clearly indicated by the results of a study in which “pre-menopausal women with low progesterone levels were found to have 5.4 times the risk of developing breast cancer, when compared to pre-menopausal women with normal progesterone levels.”  

Progesterone vs. Progestins 

The progesterone hormone and its synthetic analogs, known collectively as progestins or progestogens, are not the same molecular structure and, therefore, do not behave in the same way in the body. Progestins were developed because of a mistaken belief that progesterone could not be easily administered as an oral drug. Progestins are now the “basis of all contraceptive pills and gave rise to a multibillion-dollar industry,” according to Dr. Katharina Dalton. When progestins were first developed, researchers and practitioners noted significant differences. 

Progesterone is essential for maintaining pregnancy, while the use of progestins during pregnancy does not. We now know that progestins are associated with fetal abnormalities.  

Progesterone lowers blood pressure and progestins raise it.  

Progesterone raises the level of sex hormone-binding globulin (SHGB) and progestins lower it.  

Progesterone is converted by the adrenal glands into all the various corticosteroids, while progestins are not.  

Progesterone promotes calmness and progestins do not.  

Progesterone is hydrophobic, meaning it relieves water and sodium retention, whereas progestins are hydrophytic, meaning they attract and hold water. According to Dr. Phyllis Bronson, this primary difference explains why so many women on the Pill and other conventional progestin-based hormones are prone to edema (water retention), which can result in “brain fog” or feeling bloated.  

Finally, there are no known side effects to an excess of progesterone. 


Immediately after a woman conceives, radical changes occur. For one, a new organ – the placenta – is formed in the womb. This is the hormonal pathway between a mother and her developing baby and is usually fully developed by about the fourth month of pregnancy. Once the placenta is formed, another radical change takes place: the placenta produces approximately forty times the woman’s normal amount of progesterone. Dr. Dalton explains that the morning sickness or vomiting typically experienced in those first few months “is a sign that the ovarian progesterone is insufficient, and the placenta is not yet secreting enough progesterone.”  

Progesterone is essential for maintaining a healthy pregnancy. A condition known as preeclampsia (or toxemia) is relatively common, occurring in about 5 percent of all pregnancies and, more frequently, in first pregnancies. Symptoms include a sharp rise in blood pressure, protein in the urine, and blood changes, all of which signal the potential for more serious problems for both mother and baby. Administering progesterone to women with these symptoms, significantly reduces the rate of preeclampsia. According to Dr. Alan Beer of the Chicago Medical School, progesterone “is necessary for the safe maintenance of pregnancy and all pregnancies will fail if progesterone production is too low.”  

The children of women who supplement progesterone (not progestin) during pregnancy tend to be advanced. In a study conducted at the City of London Maternity Hospital, the children of mothers who received progesterone during pregnancy stood and walked earlier, were above average in academic subjects such as verbal reasoning and arithmetic, and did better at school overall. In addition, a significantly higher percentage of those children continued to college, when compared to the national average. The children of mothers who received progesterone in the earlier months of pregnancy seemed to benefit the most.  

At Birth  

Another sudden, radical change in progesterone occurs at the birth or delivery of the baby. Dr. Dalton explains that, at birth, “the placenta comes away from the womb, and suddenly, within twenty-four hours, the high level of progesterone in the mother’s blood drops to nearly zero.” 

At this point, the mother’s breasts begin to produce milk, stimulated by another hormone, prolactin, which also delays the menstrual cycle until after breastfeeding has stopped. After the euphoria of pregnancy and finally holding her baby in her arms, many women experience highly emotional days, with unexpected tears of emotion or even bouts of “the blues” as they adjust to their new life. However, about 10% of women experience a condition known as postpartum depression according to Dr. Dalton.  

Typical symptoms include high emotion and tearfulness plus anxiety, irritability, confusion, and possibly even hallucinations, along with an inability to sleep. In severe cases, the mother may even reject or cause harm to the baby. Fortunately, postpartum depression is linked to a progesterone deficit and can be prevented by administering progesterone immediately after delivery, and continuing with supplements, as needed after that including while breastfeeding, according to Dr. Dalton. In fact, she adds, “progesterone enhances lactation, which is an additional bonus.”  


The first menstruation, also known as menarche, is an important milestone in any girls’ life and signals that she is about halfway through puberty. The first period of menstrual bleeding usually lasts about five days but can vary between three and eight days. 

Irregular menstrual patterns are quite common for young girls until they begin to ovulate, which generally occurs about two years after menarche. Initially, ovulation may not occur every month, but about every two or three months, with the cycle becoming more regular over time. Progesterone is only released by the ovaries when ovulation occurs.  

The Reproductive Years  

With the onset of ovulation, painful menstrual cycles with heavy or irregular bleeding may begin.  Sufficient levels of progesterone and estrogen hormones are needed to maintain a healthy, regular bleeding cycle. One of the estrogen hormones, estradiol, reaches its peak during the first half of the menstrual cycle, while progesterone peaks are mid-cycle when ovulation has occurred. The timing of those peaks regulates the menstrual cycle.  

Dr. Lee and others agree that progesterone supplements can be used to re-establish the regularity of the menstrual cycle. Some women who are put on low-dose birth control pills that contain synthetic estrogen and progestin (not progesterone) to help regulate their menstrual cycle or relieve painful symptoms, but progestin does not help and can make the symptoms worse.  

Premenstrual syndrome (PMS) is known to be a hormonal condition primarily related to the timing of the spike of progesterone levels in the menstrual cycle. Dr. Bronson states that during the two weeks prior to menstrual bleeding (the luteal phase) “there is often too much estrogen to be mediated by the body’s available progesterone.” Dr. Lee concurs that PMS symptoms are most often “an individual reaction to estrogen dominance secondary to relative progesterone deficiency.” Both promote that additional progesterone is essential to balance the estrogen excess. 

This relationship is clearly demonstrated by PMS symptoms generally easing during pregnancy when high levels of placental progesterone are present and recur almost immediately after pregnancy when there is a sudden loss of placental progesterone.  

However, maintaining optimum hormone levels also requires the proper functioning of the receptors. Progesterone receptors are sensitive to many factors, including stress, and will not work properly when adrenaline (a stress hormone) is present or if blood sugar levels are low (hypoglycemia). In addition, progesterone receptors can be blocked preventing progesterone from doing its job.  

Some practitioners believe that PMS does not occur in anovulatory cycles (one without menstruation), so they recommend treatment by suppressing ovulation with low-dose birth control pills. However, the progestins in those pills may still cause PMS-like symptoms, which can be as bad or worse than the symptoms the treatment is designed to relieve. Dr. Dalton suggests that it is better to correct the progesterone imbalance.

Polycystic ovary syndrome (PCOS) is the result of a hormone imbalance whereby a woman’s menstrual cycle is dominated by increased estrogen and androgen production. Without adequate progesterone, the ovary does not release the egg, and the follicle could become a cyst. Dr. Lee claims that “If progesterone levels rise each month, as they are supposed to do, this maintains the normal synchronic pattern … PCOS rarely, if ever, occurs.”  

PCOS may start during adolescence but is usually not detected until women are in their late 20s or 30s because it takes a long time for symptoms to develop. It is the most common cause of infertility in women today. 

Progesterone – not progestin – has been proven effective for inducing fertility when there appears to be some sort of ovulatory dysfunction. Evidence indicates that progesterone therapy poses no risk, is likely to benefit those wishing to become pregnant, and may help maintain a pregnancy through the early months. Dr. Alan Beer notes that women who have low levels of progesterone tend to suffer from infertility or miscarriages. He suggests that these women “require progesterone supplementation to bring them into the safe levels.”  

Progesterone has been heralded in the field of in vitro fertilization, where it is essential for successful implantation, and where progestin cannot be used. The progesterone used has the same molecular structure as the progesterone produced by the body’s own placenta and ovaries.

Many healthcare practitioners prescribe only estrogen, with no progesterone, for a woman who has had a hysterectomy, with the mistaken belief that progesterone’s only role is protection against endometrial cancer. While she may no longer need that protection, her body still needs progesterone after a hysterectomy. Dr. Dalton wrote that women with hysterectomy need more progesterone than those with natural menopause.

Dr. Mitchell Fleisher states that women who use estrogen supplementation should also use progesterone, whether or not they have a uterus. Estrogen promotes the proliferation and enlargement of hormone-sensitive cells. Progesterone is essential to slow this proliferation and promote normal cell development.

Estrogen and progesterone work in harmony throughout a woman’s life (not just during the reproductive years) to foster and protect both emotional well-being and physical health. Maintaining the proper balance between estrogen and progesterone in both pre-and postmenopausal women has been shown to provide significant protection against PMS-related and perimenopausal symptoms, breast cancer, osteoporosis, and cardiovascular disease. These hormones, together, also directly affect the neurotransmitters that regulate mood, appetite, sleep, and pain perception.  

After the Reproductive Years  

Irregular menstrual bleeding typically occurs at the beginning or end of a woman’s reproductive phase, when hormones are in a state of flux. During these life phases (i.e., puberty and perimenopause), irregular bleeding is usually caused by insufficient levels of progesterone and sometimes low estrogens resulting in no ovulation. The lack of ovulation means that there is no progesterone production during the second half of the menstrual cycle, resulting in irregular bleeding. Women who do not ovulate tend to have more irregular periods.  

Progesterone (sometimes combined with estrogens, depending on the reason for the abnormal bleeding) helps prevent erratic periods and heavy bleeding. According to research conducted at the Mayo Clinic, progesterone therapy is effective in treating irregular bleeding, especially for women in perimenopause. Dr. Susan Lark concurs that progesterone is “the most effective medical treatment available for women in menopause transition.”  

Dr. Bronson conducted a landmark study on the role of natural, biologically identical progesterone in maintaining “quality of life” in women at mid-life. Dr. Bronson reported that anxiety was “more extreme during the luteal phase, or the latter two weeks of the menstrual cycle. Even though objectively this is when there is a gradual natural increase in progesterone production.” The results indicated that not enough progesterone was available to mediate the estrogen excess. This progesterone deficiency contributed to “mid-life anxiety patterns” and the “changes in serum levels clearly correlated with the qualitative input” provided by the women. 

In other words, when progesterone and estrogen were in balance, perception of quality of life improved and contributed to emotional well-being.  Bronson’s findings were validated by another study conducted by researchers at the Mayo Clinic who examined the quality of life between two subject groups, one of which received a progestin (medroxyprogesterone acetate), and the other received micronized progesterone. The group receiving progesterone reported significant improvements in their perception of their symptoms, including “vasomotor symptoms, somatic complaints, and anxiety and depressive symptoms.” The findings demonstrate significant differences in how progestins and progesterone behave in the body.

Progesterone contributes to a lifetime of overall health and well-being. Progesterone is necessary for balancing or facilitating many other hormones and nutrients and is pivotal to almost all other hormone activity in the body. 

With such far-reaching repercussions, it seems obvious that the need for progesterone spans the entire lifetime, affecting all life stages, and that a chronic deficiency can lead to a wide range of health issues. Fortunately, a progesterone imbalance can be treated. 

Author Bio: Carol Petersen, RPh, CNP, is an accomplished compounding pharmacist with decades of experience helping patients improve their quality of life through bio-identical hormone replacement therapy. She graduated from the University of Wisconsin School of Pharmacy and is a Certified Nutritional Practitioner. Her passion to optimize health and commitment to compounding is evident in her involvement with organizations including the International College of Integrated Medicine and the American College of Apothecaries, the American Pharmacists Association and the Alliance for Pharmacy Compounding. She was also the founder and first chair for the Compounding Special Interest Group with the American Pharmacists Association. She serves as chair for the Integrated Medicine Consortium. She co-hosts a radio program “Take Charge of Your Health” in the greater New York area. She is on the Medical Advisory Board for the Centre for Menstrual Cycle and Ovulation Research ( To contact Carol click here

As with anything you read on the internet, this article should not be construed as medical advice; please talk to your doctor or primary care provider before making any changes to your wellness routine.

Content may be edited for style and length.

Materials provided by:

Once a Month: Understanding and Treating PMS by Katharine Dalton, MD; Hunter House, Inc., Alameda, CA; 1999.  

Natural Progesterone: The Multiple Roles of a Remarkable Hormone by John R. Lee, MD; BLL Publishing, Sebastopol, CA; 1993.  

Progesterone in Orthomolecular Medicine by Ray Peat, Ph.D.; 1993.  

“A Review of Current Research on the Effects of Progesterone” by Diane Boomsma, RPh, FIACP,  

and Jim Paoletti, RPh, FIACP, in the International Journal of Pharmaceutical Compounding, Vol.6,  

No. 4, 2002.  

“Progesterone therapy in women with complex partial and secondary generalized seizures” by Andrew G. Herzog, MD, MSc, in Neurology, Vol.45; 1995.  

Common Sense Guide to a Healthy Heart by John R. Lee, MD; Hormones, Etc., Inc.; 1999.  

“Progesterone Levels During Pregnancy” by Alan E. Beer, MD; Paper published by Finch University 

of Health Science, Chicago Medical School, Chicago, IL; 2001.  

“Prenatal Progesterone and Educational Attainments” by Katharina Dalton; British Journal of  Psychiatry, Vol.129, 1976.  

“Mood Biochemistry of Women at Mid-life” by Phyllis J. Bronson, Ph.D., Journal of Orthomolecular Medicine, Vol.16, No.3; 2001.  

“Comparison of Regimens Containing Oral Micronized Progesterone or Medroxyprogesterone  Acetate on Quality of Life in Postmenopausal Women: A Cross-Sectional Survey” by Lorraine A.  Fitzpatrick, Cindy Pace, BS, and Brinda Witta, Ph.D., in the Journal of Women’s Health & Gender- Based Medicine, Vol.9, No.4; 2000.  

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