Dr. Jerilynn C. Prior answers FAQ's from Perimenopausal Women
1. My doctor has prescribed Clonidine 50mg and Prometrium 100mg daily to treat my hot flushes. Should I start both?
In general, it is important to do 'one at a time' when trying out medications or any intervention for a symptom or a problem. If you decide to take both drugs, I would try one for at least a month before adding the other.
To date, there is no study showing that clonidine controls perimenopausal hot flushes although it may be effective for menopausal ones. Keep in mind that clonidine has side effects of dry mouth and decreasing your blood pressure.
In a previous study conducted at CeMCOR, we found that Prometrium 300mg at bedtime daily was effective in reducing number and severity of hot flushes and night sweats for menopausal women. We are currently conducting the same study to see if this dose of Prometrium is effective for perimenopausal hot flushes and night sweats in perimenopausal women.
2. Does progesterone cause hair loss?
First, we must make a distinction between progestin (synthetic progesterone which is derived from chemicals) and progesterone (natural progesterone which is derived from plant sources and is the same as the progesterone produced by a woman's ovaries.) Progestins are often built from male hormones and thus are androgenic (have male hormone actions). Some may cause hair loss, especially if a woman has a family history (father, grandfather, brother) of balding. Progesterone does not act at all through androgen receptors; in fact, it is really an androgen blocker. Therefore, progesterone does not cause hair loss.
This question is often raised because of the results from the randomized controlled trial conducted by the Women's Health Initiative with 16,000 menopausal women (1 year past last flow) on hormones versus placebo for over five years. The results showed that estrogen with medroxyprogesterone (synthetic progesterone, progestin) increased risk of breast cancer in menopausal women.
We must first make the distinction between synthetic progesterone (also known as medroxyprogesterone or progestin) and natural progesterone (also known as Prometrium®.) Synthetic progesterone (medroxyprogesterone, progestin) increases cell proliferation (and potentially breast cancer) by acting through the cortisol rather than through the progesterone receptor. Natural progesterone acts to decrease the proliferation of breast cells and to make them more mature by acting through the progesterone receptor – this should be an anti-cancer action.
A large observational study (E3N Study) conducted in France, with 80,000 menopausal women over 8 years showed that treatment with estrogen alone increased breast cancer risk by 29%, treatment with estrogen and synthetic progestins increased breast cancer risk by 69% but that treatment with estrogen and natural progesterone (Prometrium®) was associated with no increased risk in breast cancer. This was not a randomized controlled trial but the results fit with results from controlled trials of breast cells in women thus these are strong data.
4. I have not had a period in several months. Will starting progesterone bring my periods back?
Good question! Whether or not progesterone will 'cause' flow in perimenopause is totally dependent on whether estrogen has been present to stimulate the lining of the uterus to thicken or proliferate. Therefore, it is possible that taking progesterone may bring back flow, however, it can be expected that flow will be lighter. Keep in mind that having this flow has the positive aspect of preventing endometrial hyperplasia (thickening of the lining of the uterus) which can be a precursor to cancer.
Nausea is caused by high estrogen levels that are often present in perimenopause. For some women, for reasons that are not entirely clear, nausea is worse in the first few days after starting progesterone. This subsides within a week or so. I don't believe it is the progesterone that is causing the nausea but rather some cross-talk with our own high estrogen levels.
6. Does progesterone suppress the levels and actions of estrogen?
In usual doses and timing, progesterone doesn't suppress estrogen. That is especially true in perimenopause when estrogen is in "overdrive."
Estrogen and progesterone work together throughout our bodies. They are both part of a system with many complex interactions. Estrogen and progesterone both work in our heart, bones, brain, breasts, uterus and vagina. Progesterone's 'job,' wherever it is acting, is to counterbalance or to complement the actions of estrogen.
Progesterone's actions are in some ways dependent on also having normal estrogen levels. For one thing, estrogen increase the presence of progesterone receptors (through which progesterone "talks" to cells.) Also, in the normal menstrual cycle, progesterone cannot be made unless estrogen has first reached its high midcycle peak. This high estrogen peak stimulates the peak of luteinizing hormone that triggers ovulation (release of an egg) and the high progesterone levels during the second phase of the menstrual cycle (luteal phase).
Estrogen levels, in turn, can be suppressed by high, non-physiological doses and timing of progesterone. For example, progesterone given early in the menstrual cycle can prevent the brain from producing the luteinizing hormone peak described above. All hormonal contraceptives work to suppress both estrogen and progesterone. For example, DepoProvera® (synthetic progesterone called medroxyprogesterone), is given as an injection that will usually suppress estrogen and progesterone for three months. So, yes, this synthetic progesterone (progestin, medroxyprogesterone) in big doses lowers our own estrogen levels.
Also, in many tissues, progesterone increases the metabolism (inactivation) or excretion (elimination) of estrogen. Natural progesterone (Prometrium®) taken as treatment for hot flushes and night sweats, in a dose of 300mg at bedtime, keeps the progesterone blood level at or above the luteal phase level. This dose of progesterone will not suppress estrogen levels in menopausal women because their levels are already low. Also, this dose will likely partially suppress estrogen in the normal menstrual cycle (pre-menopause) but would not suppress it in perimenopause when the normal feedback systems are no longer working.
Estrogen is a very powerful growth stimulator of cells and thus is important for the health of both men and women. In addition, it indirectly holds bone resorption (removal of old bone) in check to prevent excess bone loss. Estrogen plays positive roles in most tissues but if its growth stimulation is not held in check, it can promote cells to transform into cancer and also stimulate cancer growth.
Progesterone (pro=for, gest=pregnancy) is absolutely essential for becoming pregnant and for maintaining that pregnancy to full term. Progesterone also acts in the breasts, brain, bones, skin and every organ and tissues of women's bodies. Progesterone, like estrogen, stimulates cells to grow and multiply but only for about three days – longer durations of progesterone cause cells to become more mature. Progesterone then stops cell overgrowth thus it would decrease cancer risk. For example, for bone health in menstruating women, menstrual cycles need to be of normal length (about 3 – 5 weeks apart) and regular to make enough estrogen, allow ovulation and make enough progesterone for at least 10 – 12 days. Estrogen stops excess bone loss and progesterone promotes formation of new bone (by stimulating bone forming cells called osteoblasts.)
High levels of both estrogen and progesterone are normally only made by the ovary or by the placenta during pregnancy. However, steroid hormones (as are both progesterone and estrogen) are also normally made in the adrenal glands. Progesterone is high on the steroid pathway just after cholesterol but estradiol (estrogen) is much farther down and can be made directly by ovaries or by conversion from testosterone or other male hormone like steroids (such as DHEA or androstenedione). Although many tissues (fat, muscles, ovaries and adrenals) make an enzyme that can convert male hormones into estrogen, there is no known direct conversion of progesterone into estrogen.
9. Does progesterone cause weight gain and increased facial hair?
Progesterone does not cause weight gain. Progesterone does not increase facial hair. Both weight gain and increased facial hair are things that may occur when taking synthetic progesterone-like drugs that are properly called "progestins" but are sometimes mistakenly called "progesterone" even in medical publications and by doctors.
About weight gain
If anything, natural progesterone will help with weight loss. Why do I say that? First because progesterone makes us burn about 300 more calories (kCal) a day because it raises our core temperature about 0.2 degrees C. and that requires energy. (Professor Susan Barr and I showed this in a diet diary study because premenopausal women, who didn't change weight across one cycle, who ovulated and made progesterone ate 300 calories more than those women who didn't ovulate.) Also, we recently completed a randomized placebo-controlled study in healthy menopausal women and the women on progesterone didn't change weight any differently than the women on placebo. They also didn't change in waist circumference. So progesterone will not make you gain weight, and it may even help you lose weight.
About increasing facial hair
Most of the progestins (ones that are used with estrogen in the birth control pill and in progestin-only pills) except medroxyprogesterone (also called Provera) are created from a testosterone chemical base! That's why there is a real concern about them and male hormone side effects like making more facial hair.
I have not formally tested facial hair and progesterone but I have lots of personal (I needed progesterone for intense perimenopausal and menopausal hot flushes and took it myself for seven years) and clinical experience with it. In addition, I have studied how it decreases facial hair because I used it to treat women with anovulatory androgen excess (AAE, also called PCOS) for whom increased facial and male pattern body hair are a big problem. I know it decreases facial hair from that experience—here's how it works: 1) It suppresses the pituitary hormone called luteinizing hormone (LH) that stimulates the theca (outer coat of the ovary) that normally makes male hormones during the menstrual cycle; and 2) it directly inhibits the production of dihydrotestosterone, the hormone that stimulates male-type hair growth by competing for the enzyme that converts it from testosterone. Therefore I'm sure that progesterone will not cause you to have increased facial hair.
10. Are there any withdrawal symptoms when you stop taking bio-identical progesterone?
The short answer is 'no.' When you stop progesterone your hot flushes and night sweats will slowly return to their previous levels. One time, when stopping progesterone, you will find that they have gone away! Hot flushes and night sweats do eventually end.
The most common 'side effect' is increase in soundness of sleep, although not all women experience this. If a woman takes progesterone and goes to sleep and for some reason (like a full bladder) awakens her within four hours, she may feel dizzy or groggy.
There are basically no other expected side effects from bio-identical progesterone.
