ABOUT THIS MONOGRAPH
This very brief “paper” on progesterone is a condensation of a lot of information, especially regarding the activities and functions of progesterone in the human body.
It is intended to provide “lay” persons with the basic information they need to understand the hormone, cooperate with their functional medicine practitioner and make more confident decisions about their own healthcare.
If you need more information, or a deeper understanding of hormonal imbalances, check the other titles in this website, or see “you and your hormones”, at https://www.yourhormones.info/hormones/.
The site is an amazingly detailed, in-depth, all–encompassing review of all the human hormones, great for a scientific “take” on the subject.
It’s too complicated for the casual reader, but it’s useful if you need it.
PROGESTERONE GENERATES ALLOPREGNANOLONE
The hormonal action of progesterone was discovered in 1929, following the discovery of estrogen in 1923. It was named thus: PRO – (meaning for, or supportive of) – GEST (short for “gestation”, meaning “pregnancy”) – ERONE (hormone).
So progesterone is the pregnancy hormone, but it’s much, much more than that.
In the brain, Progesterone generates Allopregnanolone, which is why Progesterone puts you to sleep, helps keep brain cells healthy and gives you that happy, satisfied feeling……… but more on that, later!
Progesterone must not be confused with “progestins”.
Progestins are synthetic pharmaceutical chemicals, which possess properties similar to those of progesterone but which are known for their propensity to promote breast and uterine cancers, large vein blood clots, heart attacks and strokes.
Do check the link above, to have a look at the Wikipedia page on Progestins: the interesting thing about this Wiki page is that it avoids making a clear statement regarding the reasons why doctors don’t want to deal with “hormones” (see “NON-HUMAN PROGESTERONE”, below)..
Several pages down the article, you will find these two interesting statements:
[1] “the risk of coronary heart disease was greater with the combination of estrogen plus a progestin (specifically, Equine (horse) Oestrogen, plus medroxyprogesterone acetate) than with estrogen alone” …….and …….. “strong evidence that the treatment of post-menopausal women with (synthetic) hormone therapy for cardiovascular disease had little if any effect (on the heart), but increased the risk of stroke and venous thromboembolic events.“
[2] “With 20 years of use, breast cancer incidence is about 1.5-fold higher with estrogen alone and about 2.5-fold higher with estrogen plus progestogen therapy.”[151] The increase in breast cancer risk was shown to be due to the horse- estrogen plus synthetic progestogen therapy (conjugated horse estrogens plus medroxyprogesterone acetate) in the Women’s Health Initiative randomized controlled trials “
In the human body, progesterone is produced from pregnenolone, which is made from cholesterol.
The progesterone then generates Allopregnanolone, the “king of the brain hormones”.
This human hormone, progesterone, produced in very large quantity by the ovaries, the placenta and the brain, is often under-produced: The menstrual disorders so often seen in teenage girls usually result from progesterone deficiency.
However bioidentical progesterone, precisely identical to human progesterone in chemical structure, can be very inexpensively produced from diosgenin (diosgenin is a chemical found in wild yam which can also be processed into the entire sequence of human “neurosteroid” hormones).
PROGESTERONE IS INDISPENSABLE IN HUMAN BODY SYSTEMS
Progesterone is in many ways the body’s most interesting hormone.
Certainly, it is the most surprising hormone.
Progesterone normalizes the menstrual cycle and is necessary for pregnancy, so we have always thought of it as the pregnancy hormone, but:
It’s great for sleep.
It improves memory.
It supports kidney function.
It acts to prevent breast cancer.
It opposes weight gain, which oestrogens produce, so it is also prescribed to improve the progesterone/oestrogen balance, for weight loss.
In the brain Progesterone generates Allopregnanolone, so the effect of taking it is immediate improvement of all the functions of that amazing, indispensable king of the hormone family. (Allopregnanolone promotes normal sleep patterns, does brain maintenance, repairs demyelinated nerves, helps to control pain, enhances self-image, and improves cognition and memory. It is antianxiety, prosocial and antidepressant, thereby cancelling the effects of stress and preventing high blood pressure and its problems.
Males produce little progesterone, which perhaps is the reason for women’s advantage in the memory department.
Importantly, neither men nor women make enough progesterone after menopause/andropause.
PROGESTERONE DEFICIENCY
Progesterone deficiency can start at any age, even in the teenage years, in both females and males.
Progesterone deficiency causes menstrual irregularity, PMS and infertility in women, and in both sexes it is a cause of insomnia, poor self-image and loss of “tranquility”.
Especially when combined with other deficiencies, progesterone deficiency is a cause of anxiety, depression, fuzzy thinking, memory loss, confusion and possibly, MS and Alzheimer’s disease.
THERAPY FOR PROGESTERONE DEFICIENCY
A nightly dose of progesterone, taken with melatonin*, maintains enough progesterone and Allopregnanolone in the brain, for brain maintenance and repair.**
Some practitioners believe, as I do, that maintaining progesterone at adequate levels will prevent, or retard, development of Alzheimer’s and other neurological diseases.
* Melatonin is hypnotic, chronobiotic, antidepressant, pro-cognitive, anxiolytic and analgesic. It neutralises reactive oxygen and nitrogen species and increases antioxidant defenses.
In this way, it clears brain inflammation and helps Allopregnanolone to work.
** Progesterone, if administered quickly after a stroke, concussion or brain/spinal-cord injury, minimises nerve cell damage (this, again, is a function of the combination: Progesterone/Allopregnanolone/Melatonin, the “three musketeers” of the brain) ***.
*** The three musketeers need help from DHEA, Testosterone, Oestrogen, T3, Vitamin D and the essential vitamins and minerals, but the title sounds great, doesn’t it?
PROGESTERONE IN THE MENSTRUAL CYCLE AND IN PREGNANCY
A relatively small amount of Progesterone is made in the adrenals and ovaries.
The ovary makes a lot of progesterone, starting on the 13th-14th day of the menstrual cycle, to prepare the lining of the uterus (the endometrium) for implantation of a fertilised egg.
The progesterone level peaks on the 21st day and if no egg has been implanted in the uterus by then, the egg cyst shrinks and the blood progesterone level falls to baseline by the 28th day.
Without Progesterone, the endometrium can’t keep going and menstruation begins.
If an egg is produced, fertilised and implanted, it produces “HCG” (see below), which causes the cyst to mature into a progesterone factory, called the corpus luteum.
The corpus Luteum continues to make large amounts of progesterone, to keep the endometrium fertile until the baby’s placenta takes over hormone production, at about 8-12 weeks of pregnancy.
Figure 2: graph of Progesterone levels in the menstrual cycle.
NORMAL PROGESTERONE LEVELS
In men, and in women during the first 7 to 10 days of the menstrual cycle, the progesterone level is low (< 6 ng/ml) *.
In women of childbearing age, progesterone production begins to rise at day 14 of the menstrual cycle and after ovulation it rises rapidly to 30–50 ng/mL
If a pregnancy starts, a hormone called human chorionic gonadotropin (“HCG”) is released by the fertilised egg.
HCG converts the egg sac in the ovary into a “corpus luteum”, which produces enough progesterone to maintain the pregnancy until the placenta begins to produce its own supply, at 8–12 weeks.
The placenta keeps producing large amounts of progesterone (enough to keep the blood level up to 100–200 ng/ml) until a day or two before the baby is born. **
Then the blood progesterone level falls to its baseline level *** and stays down while the mother is breastfeeding.
* It has been suggested that women have better memories than men do because they make more progesterone. I agree; my memory improved when I started taking it.
** The sudden drop in Progesterone availability is the trigger for “parturition” (birth).
*** If the progesterone goes low enough to cause Allopregnanolone deficiency, serious postpartum depression may ensue, needing treatment with Allopregnanolone
(trade name “Zulresso), or progesterone.
Caveat: Zulresso (approved in 2019) is very expensive and Progesterone is not.
A new, oral form of Zulresso, “Zuranolone”, has been approved (2023), but the least expensive supplement for Allopregnanolone is PEA (Palmitoylethanolamine), which is available in health food stores.
PROGESTERONE DEFICIENCY
Progesterone deficiency does not normally begin until menopause or andropause.
However it can start at any age, perhaps as a sequel to childhood PTSD.
Any woman who suffers from PMS, menstrual irregularity, oligomenorrhoea (abnormally light menstruation) or menorrhagia (abnormally heavy menstruation) may be deficient and should check her “peak” blood progesterone levels.
The best time to check is between the 20th and 22nd day of her cycle (see Fig.2).
If low progesterone is confirmed, supplementation with progesterone pills,* or cream, can be very helpful.
* Some Progesterone-deficient women do well with 100mg of Progesterone each night, but many need 200 or 300mg. …… Doctors often suggest that young women should take their Progesterone supplement from the 15th to the 25th day of the menstrual cycle, so as to mimic the normal progesterone production.
However postmenopausal people with insomnia do better by taking it every night.
PROGESTERONE PREPARATIONS
Progesterone can be prepared as a cream, sublingual tablets or troches.
Some practitioners prefer creams, but usually it is prescribed as capsules.
Capsules are more convenient to take, are guaranteed to be of uniform dosage and are not liable to transfer to a partner, as a skin cream is.
The usual dose is 100–300 mg for women and 50–100 mg for men.
The dose of cream is usually only 1/3 of the oral dose, because progesterone absorbed transdermally (through the skin) enters the blood immediately.
If it is taken by mouth and absorbed from the bowel, it passes through the liver, which destroys about 60 % of the dose.
Progesterone should be taken an hour before bedtime, with 3–10 mg of Melatonin.
Of the two, Progesterone is better for sleep because it generates Allopregnanolone.
Allopregnanolone is what puts you to sleep.
Melatonin is prescribed for its multiple functions, which include assisting Allopregnanolone with brain maintenance.
PROGESTERONE (PILLS) SIDE EFFECTS
BIOIDENTICAL PROGESTERONE: supposedly, progesterone side effects include nightmares, stomach upset, changes in appetite, weight gain, fluid retention and swelling (edema), fatigue, acne, drowsiness or insomnia, allergic skin rashes, hives, fever, headache, depression, breast discomfort or enlargement, premenstrual syndrome (PMS)-like symptoms, altered menstrual cycles, irregular bleeding, and other side effects.
However in my practice, 100mg–300 mg of progesterone every night for menopausal women and 50–100 mg nightly for men did not produce ANY of these side effects.
Having said that, note that the improved memory includes remembering dreams!
So the nightmares are not generated by the progesterone: They would have occurred anyway. They would have been forgotten, but are remembered because of the memory improvement by progesterone. .
Occasionally some sensitive person complains of feeling groggy in the morning, but that difficulty goes away if the dose is taken earlier, or if the dosage is reduced.
NON-HUMAN PROGESTERONE: There are many synthetic and animal-derived “progestins”, which were prescribed in the twentieth century.* As noted above, they were combined with synthetic Estrogens, or “CEE” (Conjugated Equine Estrogen).
The combination of CEE and progestins produced a range of lethal and sublethal side effects, including cancers, blood clots, strokes and heart attacks.
Because of these side effects, hormones replacement fell into such disrepute that doctors didn’t want anyone to even say, “HORMONE” !
Nowadays our doctors are beginning to recover.
They are beginning to realise that apart from the question of hormone-dependent tumours, human hormones don’t present a problem.
However the guilt response of the medical profession as a whole was overwhelming and the improvement in attitude is slow…….. very slow.
Even now, thirty years later, doctors are still afraid to accept hormone therapy.
To this day, many MDs still get so upset by the mention of hormone therapy that they refuse even to discuss the subject.
So getting a regular MD to prescribe hormone restoration is almost impossible.
* Some progestins are still supplied, as birth-control pills.
The following link is to a listing of currently available progestins.
PROGESTERONE (CREAM) SIDE EFFECTS
Skin irritation: Rare. it occurs when the cream is repeatedly applied to the same area.
Skin-to-skin transfer to an intimate partner or to a baby: this is possible, but the probability of side-effects is tiny.
The Bottom Line:
Progesterone generates Allopregnanolone and is essential to living well, sleeping well, staying slim and maintaining the nervous system.
Ask your doctor about taking it, combined with Estrogen replacement therapy (Bi-Est is best).
Don’t take estrogen by itself.
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