HRT-About Progesterone functions, low levels, progestogens in HRT
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About Progesterone

How does progesterone function in the body?
What are the effects of lower progesterone levels?
Progestogens used in HRT and NHRT
 Natural Progesterone or Progestin, some differences

Progesterone refers both to the reproductive hormone made by the ovaries and to micronized progesterone hormone products. Progesterone prepares the uterus for egg implantation, maintains pregnancy, and prevents further ovulation during pregnancy.

    A word of clarification: The terms "progesterone" and "progestin" are often used interchangeably. Many medical practitioners and scientists do not differentiate between progesterone and progestin, both of which fall into the category of progestogens. However, there are differences both in chemical structure and effect. For clarity and accuracy, ProjectAWARE feels it’s important to distinguish these differences. Therefore, throughout this site, "progesterone" means the endogenous hormone produced in the ovaries; "natural progesterone" refers to bio-identical hormone products known as micronized progesterone or natural micronized progesterone; and "progestin" refers to any of the synthetic progestogens with altered chemical structures that have progesterone-like actions in the uterus.  

An umbrella term for progesterone and the related progestins is progestogens, because all have progestational effects in the uterus.

As long as a woman is ovulating, there is progesterone produced in the ovaries. Progesterone levels naturally rise and fall during the monthly cycle. Progesterone production starts just before ovulation and increases rapidly after ovulation, during the latter two weeks of the menstrual cycle. Progesterone is vital to the survival of the embryo and fetus throughout gestation (pregnancy). In fact, a woman's progesterone levels are very high during pregnancy, along with estrogens, especially estriol.

When a woman fails to ovulate, her ovaries do not produce progesterone. This is called an anovulatory cycle. Women can begin to skip ovulations as early as the mid 30s, with the missed ovulations becoming more frequent as perimenopause approaches. While a woman's estrogen may eventually drop 40-60% at menopause, her progesterone level can drop much lower, upsetting the natural balance (although some is still being produced by the adrenal glands). By postmenopause a woman's progesterone will drop to nearly zero.

How does progesterone function in the body?

Progesterone is produced in the corpus luteum of the ovaries of menstruating women through the conversion of pregnenolone to progesterone. It is also synthesized by the placenta, is found in the adrenals and is stored in fat tissue. Whether from your own ovaries or from an external source, progesterone works in the body by traveling in the blood to tissues where there are progesterone receptors. Progesterone molecules attach to these receptors and begin their actions in the body. While the role of progesterone in opposing the cancer-promoting effects of estrogen on the endometrium is best known, and is the primary reason that progesterone/progestins are included as part of HRT in women who have not had a hysterectomy, progesterone has many other functions in the body. It counters the effects of estrogen in various parts of the body by "downregulating" estrogen receptors. It also

  • reduces anxiety and increases sleepiness
  • helps to build and maintain bone
  • slows the digestive process
  • promotes appetite and fat storage (important in pregnancy)
  • helps to mature breast tissue and prepare breasts to produce milk

Potentially negative effects of progesterone, particularly if there is too much progesterone in relation to estrogen, may include raising insulin levels, decreasing insulin sensitivity, promoting weight gain, reducing libido, and causing depressed mood.

What are the effects of low progesterone levels?

Not as much is known about the effects of low levels of progesterone as about low estrogen levels. However, low progesterone levels due to anovulatory menstrual cycles, when no progesterone is produced by the ovaries, can result in hormone imbalance, with too much estrogen in relation to progesterone. This can lead to:

  • irregular menstrual cycles
  • heavy menstrual bleeding
  • endometriosis and uterine fibroids
  • tender breasts
  • irritability and mood swings

A drop in progesterone can also cause a decline in corticosteroid production. Progesterone is a major precursor of aldosterone and cortisol, hormones which are made only in the adrenal cortex. When progesterone is no longer produced by the ovaries, the adrenal cortex and brain should take over that function, but the adrenal glands of many Western women are so depleted that they cannot produce enough progesterone to produce the corticosteroids.

Progestogens used in HRT and NHRT

In HRT, the main purpose of taking a progestogen (progesterone or a progestin) along with estrogen is to oppose the effect of estrogen on the endometrium and prevent endometrial cancer. There are two types that can be used:

  • Natural micronized progesterone: manufactured from plant sources to be bio-identical to the progesterone made by the ovaries. Available as micronized progesterone USP.
  • Progestin: any of a group of hormone products that are formulated in a laboratory from progesterone or testosterone molecules and that have progesterone-like effects on the uterus

Natural micronized progesterone is manufactured in a laboratory from plants (Mexican wild yams and soy). It is called "natural" because its molecular structure is identical to the progesterone made by the ovaries. Natural progesterone is available for use in HRT, in infertility treatment, and to treat progesterone deficiency, including dysfunctional uterine bleeding (heavy periods), in premenopausal women. There is considerable evidence that natural micronized progesterone is effective for these uses and is relatively free of side effects. The principal side effects known are due to the effects of progesterone on the brain, and include sleepiness and fatigue. Excessive progesterone in relation to estrogen can reduce some beneficial estrogen effects by downregulating estrogen receptors.

Compounding pharmacies can supply micronized progesterone in sublingual tablets, oil caps, or transdermal (skin) creams.

Progestins have progesterone-like effects on the uterus, but their chemical structure differs from naturally occurring progesterone. Progestins are also manufactured in a laboratory and are derived either from progesterone or from testosterone. The testosterone-derived progestins have more androgenic properties than the progestins derived from progesterone. Progestins are much more powerful than micronized progesterone and are used in much smaller doses. They also have a longer half-life and remain in the body longer. Different progestins have somewhat different effects, although all of them are effective in opposing the effects of estrogen on the endometrium. Progestins are used in hormonal birth control products as well as to oppose estrogen in HRT. The most commonly used progestin in HRT in the U.S. is medroxyprogesterone acetate (MPA), the progestin used in Prempro.

Examples of Progestogen Products
Natural Micronized Progesterone:
Prometrium, oil capsule
Crinone, vaginal gel
Medroxyprogesterone acetate (MPA):
PremPro, Provera and Cycrin
Norethindrone acetate (NETA):
FemHRT, Activella and CombiPatch
See a more complete list here

Natural Progesterone or Progestin, some differences

Micronized progesterone may have more benefit than progestins for lipid profile enhancement, osteoporosis prevention, and the treatment of menopausal symptoms and endometriosis. Some studies suggest that natural progesterone may be effective to treat PMS (premenstrual syndrome), but a recent review of studies using progesterone to treat PMS-related mood disorders found a lack of strong evidence to support using it for this purpose. Many of these studies used vaginal or rectal progesterone suppositories; a few used oral progesterone. There is also a lack of evidence that progesterone supplementation is helpful in treating postpartum depression; however, there is evidence that certain progestins should NOT be used to treat postpartum depression as they may worsen the condition. More research is definitely needed.

There is substantial proof that micronized progesterone is superior to progestins for use in HRT because of its relatively minor side effects compared to progestins.

To read more about the differences between progestins and natural micronized progesterone, visit these pages:


Please read on...

  What Is Hormone Replacement Therapy (HRT) and Why Would I Need It?
   What Hormones Are Used in HRT? and How Is HRT Taken?
  About Estrogen
  About Progesterone
Benefits, Risks and Side Effects of ERT, HRT, and NHRT
  HRT and Breast Cancer
  Androgens, SERMs and Other Drugs for Menopause
  What Are Some Alternatives to Standard HRT?
  Resources and References


Page uploaded September 2002




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Updated 09/29/2010