In conversations about perimenopause, we talk about estrogen a lot. We tend to mention progesterone as an afterthought — as in, “If you have a uterus, you will also need progesterone.” But in the chatter about perimenopause online, there are a lot of claims about the important role of progesterone in hormone replacement.
This dichotomy of mainstream physicians only using progesterone to protect the uterine lining for fertility and online experts touting the critical role progesterone plays in managing perimenopausal symptoms, leaves you, the reader, with questions.
What is progesterone anyway? And what does the data say about the benefits of progesterone for perimenopausal symptoms (including improving bone health, mood, and sleep)? If you don’t need progesterone because you have had a hysterectomy, should you take it anyway? Is one way of getting progesterone (IUD, through the skin, in a pill) better than another?
I’m here to help you sift through those questions and arrive at your doctor’s appointment better prepared.
What is progesterone?
Progesterone is very much what its name implies. It is a hormone that promotes gestation. During our reproductive years, progesterone stabilizes the uterine lining after ovulation so that the uterus is ready to support a developing fetus.
Progesterone is made in the corpus luteum — the temporary mass of cells left behind in the ovary after ovulation — during the second half of the menstrual cycle. After about 14 days, if an embryo doesn’t implant in the uterus, the corpus luteum involutes, and progesterone levels fall. This allows the uterine lining to shed and another menstrual cycle to begin.
If an embryo implants in the uterus, progesterone continues to be produced in the corpus luteum until the placenta can take over. During most of pregnancy, the placenta pumps out progesterone at a prodigious rate. Progesterone levels rise to about 10 times their usual level.
Because progesterone is only made after ovulation, progesterone levels are quite low in the first half of the menstrual cycle, prior to ovulation. During perimenopause, as periods space out and become irregular, so too does the ovary’s production of progesterone. And after the last menstrual period, our ovaries will no longer produce progesterone.
Progesterone at high levels is responsible for some of our least favorite symptoms both leading up to our periods and during pregnancy. It acts in the gut to slow the rate at which food moves through our gut. This can lead to heartburn and constipation. Progesterone along with estrogen contributes to breast tenderness. Premenstrual symptoms like water retention, fatigue, and mood changes are all caused at least in part by progesterone.
Why, then, would we want to add progesterone to a hormone replacement regimen?
Does progesterone help with symptoms of perimenopause?
The primary reason we add progesterone to estrogen to treat menopause symptoms is to reduce the risk of cancer of the uterine lining. Estrogen leads to a buildup of the uterine lining that if left unchecked can result in changes in the cells of the uterine lining that could progress to cancer. Progesterone prevents that buildup, thus mitigating the risk of endometrial cancer. As a result, it is recommended that any woman who is taking estrogen for symptoms of perimenopause and has not had a hysterectomy, take progesterone as well.
There are a whole host of other symptoms for which women take progesterone. They include heavy periods, sleep disruption, hot flushes, night sweats, mood changes, and bone health. But what does the data tell us about the efficacy of progesterone for those symptoms?
Heavy or abnormal bleeding
There is a great deal of data supporting the use of progesterone in the treatment of heavy or abnormal bleeding in perimenopause. Progestins — synthetic progesterone-like compounds — in birth control pills (both combined with estrogen and alone), in the form of a progestin-eluting IUD such as Mirena, and progesterone capsules have all been shown to help reduce uterine bleeding.
This makes sense because we know that progesterone prevents the overgrowth of the uterine lining. If less lining is built up, there is less lining to shed. Progesterone also stabilizes the uterine lining. This can prevent mid-cycle bleeding that some women experience.
Sleep disruption
Sleep disruption is commonly reported by women in perimenopause. In fact, the National Institutes of Health estimates that 39% to 47% of women experience sleep disturbance during perimenopause. Micronized progesterone (a form of progesterone taken in capsules by mouth) has been well-studied. In a meta-analysis of nine randomized controlled trials including data from more than 600 participants, the authors found that micronized progesterone improved total sleep time and reduced the time it took participants to fall asleep. There was a trend toward reducing sleep efficiency, but it was not statistically significant. Women who were postmenopausal seemed to benefit the most.
Hot flushes and night sweats
Collectively called “vasomotor symptoms” in the medical literature, hot flushes and night sweats are among the most common perimenopausal symptoms. Upwards of 80% of women will experience vasomotor symptoms at some point during the menopausal transition. We know that estrogen is effective in treating vasomotor symptoms, but what about progesterone?
In a recent randomized controlled trial participants were randomized to receive 300 mg of micronized progesterone at bedtime — about three times the dose typically prescribed with hormone replacement therapy — or placebo. The women who received the progesterone had about half as many vasomotor symptoms after three months compared with the start of the trial. However, there was a strong placebo effect. In fact, the women who received the placebo also had about half as many vasomotor symptoms at three months compared to baseline. A large dose of micronized progesterone was not superior to placebo for the treatment of vasomotor symptoms. However, the women who received progesterone did have more frequent side effects including nausea, muscle and joint pain, water retention, and headaches.
Mood
While using progesterone and progestins in combination with estrogen for the management of perimenopausal mood changes is studied, the use of progesterone alone is not. There is no evidence that progesterone alone improves mood symptoms, though we know there are progesterone receptors throughout the brain. Progesterone may be playing a role in the management of mood symptoms when given with estrogen. However, we need studies of progesterone alone to know for sure.
Bone health
In recent years, there has been an increased understanding of the role of progesterone in bone metabolism. Progesterone acts in the bone at the cellular level to increase new bone building, However, there are no randomized studies looking at progesterone alone in the maintenance of bone density or prevention of osteoporosis.
Is one type of progesterone better than another?
Progesterone and progestins come in a number of formulations delivered via a few different methods. What formulation you choose will likely be determined by your treatment goals. If you are taking progesterone with estrogen just to prevent overgrowth of the uterine lining, all of the available formulations will work, including progestin-eluting IUDs, transdermal progestins like those in the CombiPatch, and oral progesterone. This is also true for heavy periods, although for some women, concentrations of transdermal progestins in hormone replacement formulations may not be high enough to provide relief.
If you are looking to improve your disrupted sleep, oral micronized progesterone taken at bedtime is the formulation studied in the literature. Though other oral formulations may be effective, I would not expect the locally acting progestin in an IUD to have much effect on sleep one way or the other.
The bottom line
- Progesterone’s main role is to support a developing fetus, and it is made in the ovary after ovulation and in the placenta during pregnancy. After the last menstrual period, the body no longer makes any progesterone.
- Progesterone is a key component of hormone replacement therapy for women who have not had a hysterectomy. It prevents overgrowth of the uterine lining that can predispose women to endometrial cancer.
- Progesterone has been shown to be effective in managing heavy uterine bleeding and in improving sleep disturbance, particularly in postmenopausal women.
Progesterone alone has not been shown to reduce hot flushes and night sweats, improve mood, or reduce bone loss.
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