It is difficult to consider progesterone without also considering estrogen, since they complement each other to keep the body in homeostasis. We’ll focus, however, on progesterone, and we’ll address estrogen more specifically later.

Progesterone is one of the steroid hormones, which means that it is made from cholesterol, just as are estrogens, testosterone, cortisol, aldosterone, DHEA, vitamin D, and pregnenolone. Progesterone prepares the lining of the uterus to receive a fertilized egg cell so that pregnancy can begin and succeed. As the pregnancy progresses, it helps to keep the cervix closed so that the baby remains inside the uterus for the proper duration of the pregnancy.

The synthesis of progesterone varies depending upon the phase of the menstrual cycle in a premenopausal woman. During the first half, or follicular phase, most of the progesterone is synthesized by the adrenal glands, and is present in the serum at a level of about 1-2mg/dl. Once an ovarian follicle breaks open, releasing an egg around cycle day 14, the ruptured follicle turns into a progesterone-producing factory called the corpus luteum. This structure produces 20-40mg per day of progesterone in the second half, or luteal phase, of the cycle, giving a serum level of 10-25mg/dl.

Although progesterone has a very specific action on the uterus, there are also progesterone receptors in tissues throughout the body, and progesterone is therefore critical for the proper functioning of many tissues and organs, especially the brain, the heart and blood vessels, muscles, bone, and the breasts. Symptoms of progesterone deficiency include:

  • muscle tension
  • irritability and nervous tension
  • difficulty falling and staying asleep
  • anxiety, anger, even with outbursts of panic or rage
  • increased sensitivity to pain – joints will be more achy when progesterone is low
  • tender and swollen breasts
  • puffiness and fluid retention (progesterone is a diuretic)
  • swollen and bloated belly
  • excessive menstrual bleeding
  • reddish or swollen face
  • uterine fibroids
  • breast cysts
  • elevation of blood pressure
  • constipation
  • increased abdominal fat
  • male pattern baldness and excessive b0dy hair (too much DHT because of low progesterone)

Progesterone is best replaced orally or sublingually, as its metabolites when given orally bind to the GABA receptors in the brain to promote calming and good sleep quality. Progesterone is not well absorbed through the skin, and may not be protective of the breasts if given by that route. In a woman who is still menstruating, it is best to replace in the physiologic pattern through the month, meaning that during the first 2 weeks of the cycle the level of replacement will be lower than during the second 2 weeks of the cycle. In a menopausal woman who no longer has a cycle, it is helpful to give the progesterone at a generous dose throughout the month consistently to a target serum level of at least 10-20ng/ml.