PROGESTERONE in WOMEN HEALTH

Progesterone is one of steroid hormones which is secreted by the corpus luteum of the ovary and by the placenta, that acts to prepare the uterus for implantation of the fertilized ovum, to maintain pregnancy, and to promote development of the mammary glands. Progesterone  produced by the corpus luteum during the second half of a woman's cycle (after ovulation). It thickens the lining of the uterus to prepare it to accept  implantation of a fertilized egg. It is released in pulses, so the amount in the bloodstream is not constant. Progesterone belongs to a class of hormones called progestagens, and is the only naturally occurring human progestagen. Progesterone should not be confused with progestins, which are synthetically produced progestagens.

Progesterone production is high during the luteal phase (second part) of the menstrual cycle and low during the follicular phase (first part). The progesterone level is low also before puberty and after menopause. Supplemental sources of progesterone are available in oral and cream forms, as well as lozenges, suppositories, and injectable forms.

Progesterone induces the cyclic changes in the endometrium that allow implantation of the fertilized ovum. Progesterone is also responsible for maintenance of the uterus during pregnancy, suppression of uterine contractions until just prior to parturition and preparation of the breasts for lactation.

After menopause, some progesterone’s made in adrenal glands. As we age, we lose our hormones, and progesterone is one of the first to go. In women, progesterone declines first, then estrogen. You could suffer from progesterone loss for 15 years before you lose your period.

In our 40′s, we usually start to experience progesterone decline. Symptoms of decreased progesterone include anxiety, depression, irritability, mood swings, insomnia, pain and inflammation, osteoporosis, decreased HDL, weight gain, and excessive menstruation. Why do we gain weight with low progesterone? Estrogen is a building up hormone, and if you do not have enough progesterone to balance the estrogen you have, then you will gain weight. Estrogen without progesterone equals gaining about 10 pounds.

Progesterone Functions

Progesterone play a crucial role in:

• menstrual cycle,
• pregnancy,
• embryogenesis,
• treatment of several hormonal dysfunction,
• treatment during pregnancy,
• hormonal support in IVF. 

Progesterone and Pregnancy

After the first trimester, the placenta begins to produce its own estrogen and progesterone. This means that even if you have a normally low progesterone level, pregnancy will typically cause a dramatic increase.

Progesterone during pregnancy should increase dramatically, usually with a desired level of 10 to 16 ng/ml. This is especially important in the early stages of pregnancy. If the progesterone level in pregnancy is low, many doctors will recommend supplements to help raise them in the first trimester - creams, suppositories, or injections, but rarely oral progesterone.

A high progesterone level is desired because of the many functions it serves throughout the pregnancy. It helps build a strong endometrial wall and placenta, prepares the pelvis for birth, helps with the development of breast tissues, and restricts early lactation and contractions. However, high levels of progesterone also help cause some of the less pleasant aspects of pregnancy, such as constipation, stomach problems, and headaches.

Although it is a vital component of a healthy pregnancy, most doctors believe it is unlikely that a miscarriage can be caused by low progesterone levels. Usually, an abnormal decline in progesterone is a symptom of another factor causing a miscarriage. Still, progesterone levels can fluctuate widely, even during pregnancy, so a drop in progesterone one day may be followed by an increase the next. Also, it is very rare to have two consecutive miscarriages, so having a low progesterone level during a pregnancy that miscarried does not indicate the level of the progesterone during the next.

Progesterone subscriptions

If it is needed, doctor will subscribe progesterone/progestines which can be used as pills, shot, vaginal suppository or cream. The method of administration is best determined by availability, convenience of use and price. Absorption and duration of action will vary by the form of progesterone used.

Important to know:

	Pills - peak absorption is about 1-4 hours and is cleared by 24 hours. Taking the pills with food enhances absorption.
	Shots - usually given in the form of progesterone in oil, doses peak at about 12 hours after administration and take at least 48 hours or more to clear. There are depot forms of medroxyprogesterone acetate (Depo-Provera®) that last at least 12 weeks which gives it its contraceptive effect.
	Vaginal suppositories, cream - absorbed to peak in 4 hours and cleared by 24 hours. Sometimes mixed in cocoa butter or propylene glycol as the carrying agent. A cream is also commercially available (Crinone®).
	Skin creams - creams tend not to absorb through the skin very well but alcohol-based gels are effective with a once a day application. A 10% alcohol and propylene glycol base also seems to be quite effective and clears by 24 hours.

Reduced and Increased level of Progesterone

Progesterone acts to stabilize the tissue lining of the uterus (endometrium) so if it is absent, such as with ovarian anovulation, irregular and heavy menstrual bleeding often occurs after a period without any menstrual bleeding. Thus progesterone is used to prevent this irregularity of bleeding if it is given continuously. If, on the other hand, a onetime bolus of progesterone is given such as with a shot or with only 5 days of oral pills, then the falling progesterone levels will actually cause an estrogen-primed endometrium to slough and therefore start a menses.

Too much progesterone often causes tiredness and even sedation. This side effect can be beneficial in women with epilepsy or even uterine irritability causing preterm labor because progesterone in high doses can decrease seizure activity and uterine contractions.

Progesterone tends to promote vaginal dryness by counteracting the effect on lubrication of estrogens and it can also decrease the amount of menstruation or block it entirely by reversing estrogen effect on the growth of the uterine lining. If a woman has stopped having menses on a birth control pill, the progestogen component needs to be decreased if menstrual bleeding is desirable.

Progesterone and mood changes

The brain has both estrogen and progesterone receptors. In women who have epilepsy, seizures are known to occur more frequently during times of high estrogen (late follicular phase and ovulation) and they are decreased when progesterone is high. In this sense, progesterone acts as brain anesthetic to some degree. High doses of progesterone can be very sedating.

Women who have depression - have lower brain levels of serotonin, thus the success of medications that block the body's degradation of serotonin and allow brain levels to remain higher. Estrogens are known to block one of the enzymes (monoamine oxidase - MAO) which degrades serotonin with the result of elevating mood. Progestogens, probably more so than natural progesterone, increase MAO concentration thus producing depression and irritability. Pure progestogen treatment without estrogen, such as DepoProvera® is known to worsen depression in women who already have a tendency toward or clinical signs of depression. The combination of estrogen plus progestogens such as used in birth control pills and menopausal hormonal replacement therapy does not tend to worsen mood because the compounds are neutralizing each other. There are some women who are more sensitive to certain hormones so their doses may need to be adjusted.