What does progesterone help with?

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You and Your Hormones

What is progesterone?

Progesterone belongs to a group of steroid hormones called progestogens. It is mainly secreted by the corpus luteum in the ovary during the second half of the menstrual cycle. It plays important roles in the menstrual cycle and in maintaining the early stages of pregnancy.

During the menstrual cycle, when an egg is released from the ovary at ovulation (approximately day 14), the remnants of the ovarian follicle that enclosed the developing egg form a structure called the corpus luteum. This releases progesterone and, to a lesser extent, oestradiol. The progesterone prepares the body for pregnancy in the event that the released egg is fertilised. If the egg is not fertilised, the corpus luteum breaks down, the production of progesterone falls and a new menstrual cycle begins.

If the egg is fertilised, progesterone stimulates the growth of blood vessels that supply the lining of the womb (endometrium) and stimulates glands in the endometrium to secrete nutrients that nourish the early embryo. Progesterone then prepares the tissue lining of the uterus to allow the fertilised egg to implant and helps to maintain the endometrium throughout pregnancy. During the early stages of pregnancy, progesterone is still produced by the corpus luteum and is essential for supporting the pregnancy and establishing the placenta. Once the placenta is established, it then takes over progesterone production at around week 8-12 of pregnancy. During pregnancy, progesterone plays an important role in the development of the foetus; stimulates the growth of maternal breast tissue; prevents lactation; and strengthens the pelvic wall muscles in preparation for labour. The level of progesterone in the body steadily rises throughout pregnancy until labour occurs and the baby is born.

Although the corpus luteum in the ovaries is the major site of progesterone production in humans, progesterone is also produced in smaller quantities by the ovaries themselves, the adrenal glands and, during pregnancy, the placenta.

How is progesterone controlled?

The formation of the corpus luteum (which produces the majority of progesterone) is triggered by a surge in luteinising hormone production by the anterior pituitary gland. This normally occurs at approximately day 14 of the menstrual cycle and it stimulates the release of an egg from the ovary and the formation of the corpus luteum. The corpus luteum then releases progesterone, which prepares the body for pregnancy. If the egg is not fertilised and no embryo is conceived, the corpus luteum breaks down and the production of progesterone decreases. As the lining of the womb is no longer maintained by progesterone from the corpus luteum, it breaks away and menstrual bleeding occurs, marking the start of a new menstrual cycle.

However, if the ovulated egg is fertilised and gives rise to an embryo, the cells that surround this early embryo (which are destined to form the placenta) will secrete human chorionic gonadotrophin. This hormone has a very similar chemical structure to luteinising hormone. This means it can bind to and activate the same receptors as luteinising hormone, meaning that the corpus luteum does not break down and instead keeps producing progesterone until the placenta is established.

What happens if I have too much progesterone?

There are no known serious medical consequences of having too much progesterone. Levels of progesterone do increase naturally in pregnancy as mentioned above.

High levels of progesterone are associated with the condition congenital adrenal hyperplasia. However, the high progesterone levels are a consequence of and not a cause of this condition. Also, high levels of progesterone are associated with an increased risk for developing breast cancer.

Progesterone, either alone or in combination with oestrogen, is taken by women as an oral contraceptive (‘the pill’). ‘The pill’ works by preventing ovulation, making it nearly 100% effective in preventing pregnancy.

Progesterone is used in hormone replacement therapy to relieve symptoms of the menopause in women. There are many recognised pros and cons to hormone replacement therapy – see the article on menopause for more information.

What happens if I have too little progesterone?

If progesterone is absent or levels are too low, irregular and heavy menstrual bleeding can occur. A drop in progesterone during pregnancy can result in a miscarriage and early labour. Mothers at risk of giving birth too soon can be given a synthetic form of progesterone to delay the onset of labour.

Lack of progesterone in the bloodstream can mean the ovary has failed to release an egg at ovulation, as can occur in women with polycystic ovary syndrome.

Last reviewed: Feb 2018

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What Does Progesterone Do? The Top 8 Impacts.

Poor progesterone—it doesn’t get nearly as much attention as estrogen. Everyone knows estrogen as the “female” hormone but hardly anyone talks about estrogen’s partner in crime, progesterone. And it’s too bad, because progesterone is a super hormone with the power to help women sleep better, grow stronger, and feel more relaxed.

To increase your hormone IQ, read about the top eight impacts of progesterone.

Sustains the uterine lining

High levels of progesterone after ovulation help thicken and maintain the uterine lining. A short luteal phase (under 10 days) can indicate low levels of progesterone, which can make it harder to get pregnant.

Builds strong bones

The process of maintaining strong bones involves the removal of old bone (accomplished by cells called osteoclasts) and replacing it with new bone (created by osteoblasts). While estrogen is involved in maintaining existing bone, only progesterone can help build new bone by stimulating osteoblast activity. Both irregular cycles and short luteal phases are risk factors for bone loss.

Boosts metabolism

You know how your basal body temperature rises by a half a degree after ovulation? That’s because of rising levels of progesterone. Progesterone increases your metabolic rate, causing your body temperature to rise, increasing your appetite and energy levels.

Helps you quit bad habits

A recent study from the University of Pennsylvania showed that during the luteal phase, when progesterone was high, there was a stronger active connection between a part of the brain responsible for cravings and rewards, and a part responsible for decision making. The researchers hypothesize that the change may enhance cognitive control, making it easier to quit bad habits like smoking and drinking.

Aids sleep

Progesterone is known to help women fall asleep faster, have less disturbed deep sleep, and stay asleep longer.

Protects against breast and endometrial cancer

Progesterone counteracts estrogen’s stimulating effect on breast and uterine tissue.

It makes you constipated

It’s a muscle relaxant, so it can have a dampening effect on the normal bowel contractions that help you stay regular. High progesterone is the reason why so many pregnant women complain of constipation, and it’s also the reason why some women get constipated after ovulation.

Protects against coronary artery disease

Researchers have long pointed to estrogen as the reason why women have heart attacks when they are 10 years older, on average, than men. However, a large randomized controlled trial found no support for the idea that estrogen therapy prevented heart disease. Recent research indicates that during the 30 – 40 years of a woman’s reproductive life, normal levels of both estrogen and progesterone are needed to prevent or delay heart disease in women.

By Lindsay Meisel | May 16, 2017 Tags: luteal phase, progesterone

Lindsay Meisel

What Is Progesterone?

Sometimes called the “pregnancy hormone,” progesterone plays an important role in fertility and pregnancy.

Produced by the ovaries, progesterone is referred to as the “pregnancy hormone” because it helps a woman’s body achieve and maintain pregnancy. Dorling Kindersley/Getty Images

Progesterone is a natural hormone produced by a woman’s ovaries after she ovulates (the moment when an egg is released into the fallopian tube).

The corpus luteum, a temporary endocrine gland, secretes progesterone. (1)

Progesterone: The Pregnancy Hormone

Progesterone is sometimes called the “pregnancy hormone” because of the role it plays in getting pregnant and maintaining a pregnancy. Progesterone gets the uterus ready to accept and maintain a fertilized egg.

When a woman has her menstrual period, her progesterone level is usually low during the first few days.

But once she ovulates, her progesterone level goes up for about five days, then comes back down.

Progesterone Levels, Fertility, and Pregnancy

Progesterone is necessary for pregnancy because it gets the uterus ready to accept, implant, and maintain a fertilized egg. The hormone prevents muscle contractions from happening in the uterus that would cause a woman’s body to reject an egg.

If you become pregnant, the hormone helps create an environment that nurtures the developing baby.

Your progesterone level will slowly increase between your 9th and 32nd weeks of pregnancy. (2)

The Role of the Placenta in Progesterone Production

The placenta (the structure inside the uterus that provides oxygen and nutrients to a developing baby) will begin to produce progesterone after 8 to 10 weeks of pregnancy to help maintain a healthy environment for the baby. At this point, the placenta increases progesterone production to a higher rate than your ovaries were producing. These high levels of progesterone throughout your pregnancy cause the body to stop producing more eggs, as well as prepare your breasts to produce milk. (3)

Fertility Problems and Progesterone Tests

If you’re having a hard time getting pregnant, your doctor may recommend a blood test for progesterone to see if you’re ovulating or if your ovaries are healthy.

If your progesterone level is low but you are pregnant, your doctor may recommend a blood test to check whether your pregnancy is at risk for complications, such as miscarriage or preterm delivery. (2)

Signs and symptoms that indicate you may have a low progesterone level include the following: (1)

  • Uterine bleeding
  • Missing your periods or having abnormal periods
  • Spotting and pain while pregnant
  • Repeated miscarriages

Not having enough progesterone can also cause you to have too much estrogen. A high level of estrogen can decrease your sexual desire, cause weight gain, and affect your gallbladder.

Progesterone as a Medication and Treatment

Progesterone is part of a class of medications called progestins.

If you’re having trouble getting pregnant, or if you’re undergoing fertility treatments, your doctor may recommend that you take progesterone hormone therapy. (4)

This can be done for any of the following reasons:

  • To bring on menstruation
  • Because your ovaries don’t produce enough progesterone
  • Because medications you take are lowering your progesterone level
  • To replace progesterone that’s removed from your ovaries by certain procedures

There are several different forms of progesterone available, so talk to your doctor about which form is best for you.

Progesterone Treatment Delivery Systems

Progesterone treatments come in the following forms:

  • Vaginal gel that’s usually used once per day
  • Vaginal suppository, which can be compounded at specialty pharmacies but is not approved by the Food and Drug Administration (FDA)
  • Vaginal inserts, which the FDA has approved for progesterone supplementation, not replacement
  • Oral capsule that’s inserted vaginally (not approved by the FDA)
  • Injection, the most commonly used method, which requires daily injections in the butt

Progesterone and Hormone Therapy or Hormone Replacement Therapy

Progesterone is also sometimes taken as part of hormone replacement therapy (HRT) in women who have gone through menopause but who haven’t had a hysterectomy (surgical removal of the uterus). (4)

Hormone therapy (HT) usually includes taking estrogen to treat menopausal symptoms and reduce the risk of developing certain diseases.

Note that taking progesterone can cause side effects, including the following:

  • Headaches
  • Breast tenderness or pain
  • Vomiting
  • Diarrhea
  • Constipation
  • Tiredness
  • Mood swings
  • Irritability
  • Sneezing
  • Coughing
  • Vaginal discharge

Taking progesterone can also cause more serious side effects, such as the following:

  • Breast lumps
  • Migraines
  • Dizziness and faintness
  • Impaired speech
  • Seizures
  • Numbness in the arms or legs
  • Swelling or pain in the legs
  • Balance issues
  • Difficulty breathing
  • Accelerated heartbeat
  • Chest pain
  • Vision issues
  • Uncontrollable shaking in the hands
  • Stomachaches
  • Itchy skin or rash
  • Vaginal bleeding
  • Depression

If you experience any of these serious side effects, call your doctor.

Controversy Around Hormone Therapy

In the early 2000s, people began worrying about the risks of hormone therapy. At the time, a Women’s Health Initiative (WHI) study showed that there was a link between combined estrogen and progestin therapy and an increased risk of breast cancer and cardiovascular disease. The study also appeared to show that hormone therapy was more harmful to postmenopausal women than it was helpful, stating that estrogen alone appeared to be related to an increased risk of stroke, as well as not helpful for coronary artery disease. (5, 6)

The WHI published the results of the study in JAMA, announcing that, despite following participants for a mean of five years, study investigators had ceased the estrogen-plus-progestin portion of the study before its original stop date. The reason for the sudden end was that it was deemed unethical to continue the study because the WHI had discovered an excess risk of breast cancer in women taking the drugs. (6,7)

Then two years after the announcement, the WHI also ended the estrogen-only study before it was complete, stating that it found an increased risk of blood clots in women taking the medication. However, these women didn’t face a significant increase in breast cancer risk. (6,7)

With that said, more current analyses do not show these risks to be apparent with hormone therapy. Consider a follow-up study published in September 2017 in JAMA, which reported that neither estrogen plus progestin taken for a median of 5.6 years nor estrogen alone taken for a median of 7.2 years were associated with an increased risk of death due to all causes, cardiovascular issues, or cancer during a cumulative follow-up of 18 years. (8)

While there are different thoughts on hormone therapy, your doctor can help determine if it is an appropriate treatment for you.

Progesterone for Birth Control and Contraception

Progesterone can also help you avoid getting pregnant.

A form of progesterone, called progestin, is used in combination with estrogen in hormonal contraception such as birth control pills, vaginal rings, and the skin patch.

Progesterone is also used as birth control by itself in pill and injection form. Other types of progestin-only birth control include the birth control implant and hormonal intrauterine device (IUD). (9)

These forms of birth control protect women against pregnancy due to the following actions: (9)

  • Causing the mucus in the cervix to thicken, which makes it hard for sperm to reach the uterus and fertilize an egg
  • Stopping ovulation
  • Thinning the lining of the uterus

Talk with your doctor about which method is best for you.

Progestin-Only Birth Control Pills

Also called “mini-pills,” these may cause the following side effects:

  • Headaches
  • Nausea
  • Breast tenderness
  • Inconsistent bleeding, such as not bleeding at all, short cycles of bleeding, spotting, or heavy bleeding

Women with lupus or those who have a personal history of breast cancer should not take this form of birth control.

Vaginal Rings

Sold as NuvaRing, and coming to market as Annovera, this small ring is inserted into your vagina. NuvaRing contains estrogen and progestin. (10) Annovera is lined with segesterone acetate, a new form of progestin, and ethinyl estradiol, or estrogen.

The ring needs to be replaced every month, and if you go without it inside your vagina for more than 48 hours during the weeks you should be wearing it, you’re not fully protected from getting pregnant.

If you take any of the following, NuvaRing may not be as effective:

  • Antibiotics such as Rifadin (rifampin)
  • Grifulvin (griseofulvin), an antifungal
  • Some HIV medications
  • Some antiseizure and mental health medications
  • Saint-John’s-wort

Possible side effects of NuvaRing may include these conditions:

  • Back and jaw pain
  • Stomach pain
  • Nausea, sweating, and breathing difficulties
  • Chest pain or discomfort
  • Intense headaches
  • Vision problems, such as seeing flashes
  • Yellowing of the skin or eyes

Progesterone Patches

The birth control skin patch works like other forms of hormonal birth control in that it contains estrogen and progestin.

The patch is worn on your belly, upper arm, butt, or back, and it is replaced every week for three weeks. Then you don’t wear the patch for a week and repeat the cycle. (11)

If you take any of the medication or supplements listed as potentially problematic with a vaginal ring, the patch may be less effective as well.

Additionally, using the patch can cause the same side effects as NuvaRing.

Progesterone Shots or Injections

The birth control injection (also known as the birth control shot) is available as the brand Depo-Provera. It consists of depot medroxyprogesterone acetate and prevents pregnancy for three months.

A healthcare provider has to give you the injection. When you get your first shot, you can be anywhere in your menstrual cycle. After that time, you need to get an injection every 13 weeks, with 15 weeks being the latest you can receive it for it to be effective. If you get the injection more than 15 weeks from the last one, use other methods to avoid getting pregnant for the next seven days, such as abstaining from sexual intercourse or using condoms. (12)

Bonus Benefits From the Birth Control Shot

In addition to birth control, the injection may provide the following health benefits:

  • Cause your period to stop
  • Reduce the risk of uterine cancer
  • Protect against pelvic inflammatory disease
  • Relieve pain from endometriosis
  • Help relieve symptoms of sickle cell disease and seizure disorders
  • Reduce bleeding associated with uterine fibroids

The injection can also cause the following side effects:

  • Irregular bleeding
  • Weight gain (less than 5 pounds)
  • Delay in getting pregnant after you stop the injection (takes an average of 10 months)
  • Bone loss (some of the bone loss is regained when you stop the injections)

Call your doctor if you experience any of these side effects.

Also, if you are at risk for cardiovascular disease or have a history of stroke, vascular disease, or uncontrolled high blood pressure, talk with your doctor about whether the injection is a safe choice for you. Taking the injection can increase the risk of cardiovascular disease during and after you stop taking it. (12)

Contraceptive Implants

These arm implants provide long-term birth control via a small flexible plastic rod that is placed under the skin of your upper arm. The rod releases progestin. (13)

Having any of the following may not make you a good candidate for an implant:

  • Allergies to the materials in the implant
  • History of blood clots, heart attack, or stroke
  • Liver tumors or liver disease
  • History of breast cancer
  • Undiagnosed abnormal genital bleeding

Hormonal IUD

This type of birth control contains hormones that work in the same way as other forms of birth control. However, the IUD is a small flexible plastic frame that’s inserted into your uterus. IUDs that incorporate progestin are known by the brand names Mirena, Kyleena, Liletta, and Skyla. These IUDs can be inserted for three to six years. They can also make your period lighter or disappear altogether. (14)

Possible side effects of hormonal IUDs include the following:

  • The device may slip out of your uterus or out of place.
  • You may get an infection if bacteria reaches the uterus when it’s inserted.
  • The device may push through the wall of the uterus, requiring it to be surgically removed (this is rare)

Another kind of IUD that doesn’t release hormones is called a copper IUD or Paragard.

5 Reasons why Progesterone is critical to Conception and Pregnancy

As the name suggests, progest-erone – as in “pro-gestation” – is critical to conception and pregnancy. But we don’t hear much about this super hormone that not only indicates ovulation is occurring properly, but also prepares the uterus to receive a fertilized embryo for implantation. So why is progesterone so important when trying to conceive? Let’s find out.

Progesterone confirms ovulation. At the beginning of each menstrual cycle, progesterone levels are relatively low. First, Follicle Stimulating Hormone, or FSH, stimulates an ovarian follicle to develop, which causes an egg to mature and increases estrogen production. Then, as estrogen levels rise, FSH production declines and Luteinizing Hormone, or LH, production increases. A spike in LH levels indicates that ovulation, or an egg being released from the ovary, is about to occur. Many ovulation predictor kits measure LH, as the presence of this hormone is “predictive” of ovulation. After ovulation comes the luteal phase, where the corpus luteum produces progesterone. The corpus luteum is the empty follicle from which the egg was released. The presence of progesterone indicates that ovulation has, in fact, occurred, because if no egg is released, there is no empty follicle, or corpus luteum, to produce it!

Progesterone stabilizes the uterine lining. Each month, estrogen is released before ovulation and stimulates the uterine lining to build up. After ovulation, progesterone acts to stabilize the uterine lining so it is at the optimal thickness to support implantation. Progesterone’s role is to prepare the uterine lining for a pregnancy, allowing it to become receptive to the fertilized egg so that it can attach, implant, and thrive for the duration of the pregnancy.

Progesterone enables a fertilized embryo to implant. Since progesterone is involved in stabilizing the uterine lining, high levels of progesterone are needed for the embryo to attach in the womb. Implantation typically occurs 7-10 days after ovulation. Up until about the 8th week of pregnancy, the corpus luteum produces progesterone to support the pregnancy. After about the 8th week of pregnancy, progesterone production is taken over by the placenta and continues to nourish the fetus for the duration of the pregnancy.

Progesterone is needed to maintain pregnancy. Whether generated from the corpus luteum or the placenta, progesterone levels remain elevated during pregnancy to support a healthy uterine environment for the growing fetus. It has some side benefits too. That “pregnancy glow”? That’s mighty progesterone at work making the skin appear firmer and brighter!

Tracking progesterone shows the full picture. While traditional ovulation predictor kits are great for determining the best time for intercourse when trying to conceive, they fail to show the full picture. The menstrual cycle has 2 distinct phases. The first is the follicular phase, which is comprised of menstruation and the fertile window. This is the time leading up to ovulation. The second is the luteal phase, which is the time after ovulation and is critical for enabling conception and implantation. Progesterone is the dominant hormone present during the luteal phase. By using ovulation predictor kits to track hormones during the follicular phase and tracking progesterone during the luteal phase, women can understand both halves of their cycle and therefore, the full menstrual picture!

Up until now, progesterone testing required a blood sample, either at the doctor’s office or via mail-in kit. Proov rapid response progesterone test strips enable women to track progesterone at home, in 5 minutes, using urine instead of blood. Just collect a first morning urine sample, dip the strip, wait 5 minutes and read results! One line is positive, and two lines are negative. Proov test strips empower women to know more about their bodies and understand if their hormone levels are adequate to enable proper ovulation and conception by tracking levels of the critical female hormone: progesterone.

Progesterone could increase births in women with early pregnancy bleeding and previous miscarriage

The PRISM trial, funded by the National Institute for Health Research (NIHR) and co-ordinated by Birmingham Clinical Trials Unit in collaboration with Tommy’s National Centre for Miscarriage Research, is the largest ever trial of its kind and involved 4,153 pregnant women who presented with early pregnancy bleeding.

The women, being treated at 48 hospitals across the UK and with the average age of 31, were randomly assigned by computer into one of two groups — one group of 2,079 women were given progesterone, while the other group of 2,074 women were given a placebo.

Dr Adam Devall, Senior Clinical Trial Fellow at the University of Birmingham and Manager of Tommy’s National Centre for Miscarriage Research, explained: “Miscarriage is a common complication of pregnancy, affecting one in five women, and vaginal bleeding in early pregnancy is associated with a one in three risk of miscarriage.

“Several small studies have suggested that administering progesterone, a hormone essential for maintaining a pregnancy, may reduce the risk of miscarriage in women presenting with early pregnancy bleeding.

“The PRISM trial was undertaken to answer a very important research question; whether progesterone given to pregnant women with threatened miscarriage would increase the number of babies born after at least 34 weeks of gestation when compared with a placebo.”

While the research did not show statistically strong enough evidence to suggest that progesterone could help all women who are suffering early pregnancy bleeding to go on to have a baby, importantly the results did show the hormone benefitted those who had early pregnancy bleeding and had previously suffered a miscarriage.

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The researchers found that there was a 4% increase in the number of babies born to the women in the study who were given progesterone and had previously had one or two miscarriages compared to those given a placebo. (Of the 777 women given progesterone who had previously had one or two miscarriages, 591 (76%) went on to have a live birth, compared with 534 women out of 738 in the placebo group (72%).)

The benefit was even greater for the women who had previous ‘recurrent miscarriages’ (i.e., three or more miscarriages) — with a 15% increase in the live birth rate in the progesterone group compared to the placebo group. (Of the 137 women taking part in the trial who had previously had three or more miscarriages, 98 (72%) went on to have a live birth, compared to 57% (85 out of 148) women in the placebo group who went on to have a baby).

The ground-breaking research was published today in the New England Journal of Medicine.

Arri Coomarasamy, Professor of Gynaecology at the University of Birmingham and Director of Tommy’s National Centre for Miscarriage Research, said: “The role of progesterone in women with early pregnancy bleeding has been studied and debated for about 60 years, however what we have previously lacked is high quality evidence.

“The largest study before the PRISM trial had less than 200 participants; whereas our study had more than 4,000 participants and was of very high quality, which means we can be confident in our findings.

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“Our finding that women who are at risk of a miscarriage because of current pregnancy bleeding and a history of a previous miscarriage could benefit from progesterone treatment has huge implications for practice. This treatment could save thousands of babies who may have otherwise been lost to a miscarriage.

“We hope that this evidence will be considered by the National Institute for Health and Care Excellence (NICE) and that it will be used to update national guidelines for women at risk of miscarriage.”

Jane Brewin, Chief Executive of Tommy’s, said: “The results from this study are important for parents who have experienced miscarriage; they now have a robust and effective treatment option which will save many lives and prevent much heartache.

“It gives us confidence to believe that further research will yield more treatments and ultimately make many more miscarriages preventable.”

Tracking your period in Clue can help you know whether your cycles are irregular.

Hormones are so much more interesting than what we’re taught in health class. So we’ve created a guide to aaaall of the hormones. Here’s everything you need to know about estrogen, progesterone, androgens, progestins, synthetic estrogen, and sex hormone binding globulin (SHBG).

What is progesterone? How is progesterone produced?

Progesterone is the major hormone in a class of hormones called progestogens. Progestogens are sex hormones (like estrogens and androgens), meaning that they impact sexual development during puberty and are involved in reproduction.

Learning the importance of progesterone and how it affects your body through different life stages could allow you make sense of symptoms associated with your menstrual cycle, know when something is wrong, help you have a healthy pregnancy, or choose the best type of birth control for you. This understanding can help you advocate for yourself with your healthcare provider and make the best choices for your health.

Hormones are small molecules that are produced by glands and travel throughout the bloodstream, until they reach an organ whose cells have the particular receptors for that hormone. Progesterone targets and affects the uterus, vagina, cervix, breasts, and testes, as well as the brain, blood vessels, and bones (1,2).

Your body uses cholesterol as the building block to make progesterone. Progesterone is produced mainly in the ovaries by the corpus luteum (3), which is the area that develops after ovulation occurs and the follicle around the egg collapses. Some progesterone is also produced by the adrenal glands, which sit on top of the kidneys. During pregnancy the placenta produces progesterone (4).

What does progesterone do to the body?

  • Stops the build-up of the endometrium caused by estrogen

  • Reduces cervical mucus production

  • Inhibits ovulation when at high levels

  • Prepares the endometrium for the possible implantation of a fertilized egg

  • Supports early pregnancy and helps maintain a continued pregnancy

  • Develops the mammary glands during pregnancy in preparation for lactation

  • Decreases uterine contraction to prevent contractions during pregnancy

  • Decreases activity in the intestines, possibly causing constipation (1,2,4-6)

How does progesterone change during the menstrual cycle?

Prior to ovulation = lower progesterone

At the start of the menstrual cycle (during the period), progesterone levels are low and they remain low throughout the follicular phase (4,7).

After ovulation = higher progesterone

Progesterone is the dominant hormone after ovulation (the luteal phase). Progesterone is produced by the corpus luteum, which is the area on the ovary created by the collapsed follicle that contained the ovulated egg. Progesterone levels peak in the middle of the luteal phase (8,9). If conception does not occur, the corpus luteum starts to break down 9 to 10 days after ovulation, causing progesterone levels to fall and the period to start (1,4).

How do I know if my progesterone levels are normal?

If your levels of progesterone aren’t normal, there are some signs and symptoms you may notice.

Low progesterone

Progesterone may be low if ovulation is not occurring regularly (or at all), or if your body can not build enough progesterone.

Some signs and symptoms of low progesterone include:

  • Long or heavy periods

  • Spotting before your period

  • Irregular menstrual cycles

  • Short menstrual cycles due to a short luteal phase (4,10)

Some conditions, such as elevated prolactin (a hormone that induces milk production), hypothyroidism, or polycystic ovary syndrome (PCOS), can cause infrequent or absent ovulation, which would lead to low progesterone levels (11). In these cases, the cause of the low progesterone should be diagnosed and treated.

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Luteal phase defect

The term luteal phase defect is used to describe a condition that occurs when the body does not produce enough natural progesterone to maintain the normal function of the endometrium and support the implantation and growth of an early pregnancy (12). You may also see it called luteal phase insufficiency. Diagnosing a luteal phase defect can be difficult and there’s no single agreed upon test for it. When there is no known cause for low progesterone, there are no clear guidelines about how and when to treat it. In general there is little available information about people who have low progesterone and are not trying to become pregnant.

Low progesterone and miscarriage

Knowing the importance of progesterone in maintaining early pregnancy (13), it makes sense that low progesterone might be a cause for infertility or miscarriage. However, it is a subject of debate among researchers and healthcare providers whether or not luteal phase defect is a cause of infertility, along with how best to diagnose and treat it (12).

Low progesterone during the luteal phase does not appear to be associated with an increased risk for miscarriage. A study of 191 people showed that progesterone levels during the luteal phase were similar for people who had early miscarriages compared to those who didn’t (14). Another study that included 197 people who had experienced at least two consecutive miscarriages showed that a low progesterone level during the luteal phase did not predict who would go on to have another miscarriage (15).

Low progesterone in early pregnancy may be a symptom of a pregnancy that isn’t viable versus a cause of miscarriage. One study showed that people who experienced bleeding during early pregnancy had lower progesterone and were more likely to have a miscarriage than people who didn’t have bleeding in the first trimester (16). For people who have had multiple miscarriages where the cause is unknown, treatment with a progestogen may help prevent miscarriage—particularly in people who have had three or more pregnancy losses—but more studies are needed (17).

High progesterone

Elevated progesterone is uncommon, but it can be a sign of certain disorders such as:

  • Congenital adrenal hyperplasia (CAH)

  • A type of abnormal pregnancy called a hydatidiform mole

  • Some ovarian cysts

  • Certain ovarian tumors (18)

What are “normal” levels of progesterone during different life stages?

Progesterone levels can vary from person-to-person, but also for the same person from cycle-to-cycle. Differences in laboratory procedures, population served by the laboratory, and testing technique can also impact results—so lab results should always be interpreted using the laboratory’s reference values (7).

But here’s an idea of how levels of progesterone compare across different life stages (18). You might want to bring this with you to any appointments to compare with your healthcare provider.

What is progestin?

Progestins are synthetic hormones created from progesterone or testosterone that have progesterone-like effects (19). Progestins are used in all hormonal contraception (either alone or in combination with an estrogen) and some menopausal hormone therapy.

Because their chemical structure is slightly different from the body’s own progesterone, they’re not a perfect fit for progesterone receptors. Progestins may attach to more than just progesterone receptors in the body. They may also bind to receptors for androgens and estrogens, causing side effects associated with these hormones depending on whether the progestin activates or blocks the receptor (2).

For example, progestins that activate androgen receptors may lead to side effects like acne or hirsutism (excess hair) in some people, especially when birth control has low or no estrogen (10). Hormonal birth control (usually the pill) can also be used to treat acne and hirsutism (20,21). Not everyone’s response will be the same, but for some people the specific formulation and type of progestin will matter.

Sometimes the dose of progestin isn’t high enough or the attachment between the progestin and the progesterone receptors isn’t strong enough, causing bleeding or spotting while still taking active (hormone-containing) birth control pills or causing heavier periods (10). Sometimes a simple change in dose or type of birth control can improve these side effects. It may not always be the progestin causing the problem. In combined hormonal contraceptives, the estrogen dose may also play a role in certain side effects.

If you are having unwanted side effects that you think may be connected to your birth control, talk to your healthcare provider. Using Clue to track your cycle can help you see if there are patterns to what you’re experiencing and could help lead to a solution.

How does hormonal birth control affect the progesterone in my body?

Progesterone levels while taking hormonal birth control will depend on whether your method inhibits ovulation.

If you are not ovulating, then your progesterone levels will be low and flat (no peak).

Combined hormonal contraception and progesterone

Combined hormonal contraceptives—which include both a form of estrogen and a progestin— primarily prevent pregnancy by stopping ovulation. They also work by thickening cervical mucus (22).

The pill and progesterone

Progesterone is suppressed in people taking a variety of combined oral contraceptives (COCs) (various doses, progestin types, and regimens), indicating that ovulation does not typically occur with this method (23,24).

The patch and progesterone

In one study, progesterone levels for people using the birth control patch were lower than they were before starting the patch (25). The patch prevented ovulation in almost all cycles that it was used correctly.

The ring and progesterone

In a study of 21 contraceptive ring users, progesterone levels were consistently low (on average <0.63 ng/mL) because no ovulations occurred over the course of two months of use (24).

Progestin-only contraception and progesterone

Ovulation may still occur on some progestin-only birth control methods. This means that progesterone levels will still rise and fall in the pattern that is typical of people not on hormonal birth control. Ovulation rates among this group vary because even though they all contain a progestin, they have different types, have different dosages, and enter the body through different routes (2). This affects the amount of progestin that actually makes it into the bloodstream and up to the brain to stop ovulation.

Just because ovulation may occur on these methods doesn’t mean that the birth control isn’t working. Progestin-only methods also work in other ways, such as thickening cervical mucus so that sperm are blocked from reaching the egg (22).

The implant and progesterone

The majority of etonogestrel contraceptive implant users do not ovulate. Among 16 etonogestrel implant users who were followed for up to three years, there was no ovulation detected until after 30 months of use, when two study participants showed increased progesterone levels indicative of ovulation (26). Ovulation may occur in a minority of people after long-term use of the implant as the levels of the medication in the body decrease over time (27).

Hormonal IUDs and progesterone

Ovulation is common among people using the hormonal IUDs. In a small study of 10 people using the 52 mg levonorgestrel IUD, almost half of the cycles studied during the first year of use were ovulatory (28), but this number increases over time.

In a study of 14 people using the 52 mg levonorgestrel IUD for 6 years, ovulation occurred in 79% of the cycles even though nine of the study participants were not having regular periods (29). Regardless of whether they were having a period, the progesterone levels for these 14 people followed normal patterns of progesterone through the menstrual cycle, peaking on days 20-25, with max values in the typical range (29,18).

For people using the lower-dose hormonal IUDs (19.5 mg and 13.5 mg types), ovulation occurs in almost all cycles (22).

The shot and progesterone

The contraceptive injection or shot—which is a medication known as the depot medroxyprogesterone acetate (DMPA) injection—inhibits ovulation (22) and therefore suppresses ovarian progesterone production.

The average progesterone level for someone using the contraceptive injection is 0.40 ng/mL, (30). This level is similar to someone who is not on any form of hormonal contraception and is in the follicular (pre-ovulatory) phase of their cycle (18).

Progestin-only pill (“mini-pill”) and progesterone

In a study of 43 people taking the mini-pill containing the progestin norethindrone, 60% had low progesterone levels without the typical peak, demonstrating either no ovulation or low progesterone production from the corpus luteum (31). The remaining 40% of people likely ovulated since they had a progesterone peak of at least 5 ng/mL for a minimum of 5 days, like people not on hormonal birth control (31). The likelihood of ovulation in this group was the same at 2 months and 6 months of use (32).

What else should I know about progesterone?

Progesterone and fertility awareness based methods

Basal body temperature (BBT) is one indicator people may track when using a fertility awareness based method (FAM) for contraception. Progesterone causes an increase in BBT of about 0.5ºF/0.3ºC to 1.0°F/0.6ºC (33,34). A sustained increase in BBT is a sign that ovulation has occurred.

Progesterone and the abortion pill

The “abortion pill” (mifepristone) is an anti-progesterone medication, meaning that it binds to the progesterone receptor, but doesn’t activate it (35). This keeps progesterone from being able to exert its normal effect, which in the case of early pregnancy is to promote and support implantation of the embryo and to keep the uterus from contracting.

Mifepristone is used along with another medication called misoprostol to induce elective abortions in the first trimester (35), but also to treat early miscarriages (36).

PMC

Human chorionic gonadotropin

The most widely studied trophoblast hormone product is hCG. In pregnancy this glycoprotein is critical since it rescues the corpus luteum from involution, and this maintains progesterone secretion by the ovarian granulosa cells. Its usefulness as a diagnostic marker of pregnancy stems from the fact that it may be one of the earliest secreted products of the conceptus. In pregnancy, placental production of hCG is at its peak between the eighth to the tenth week of gestation, and tends to plateau at a lower level for the remainder of pregnancy.

The only definitely known function for hCG is support of the corpus luteum (CL), taking over for LH on about the eighth day after ovulation, 1 day after implantation, when b-hCG first can be detected in maternal blood. At 8 cell stage, hCG has been detected in the embryo using molecular biology techniques.

Implantation occurs 5-6 days after ovulation and hCG must appear by 10 days of ovulation (4 days after ovulation) to rescue corpus luteum. Hence, Blastocyst should implant in a narrow window of time. The hCG stimulation of CL has a daily secretion of 25 mg of P and 0.5 mg of E2. hCG gene expression is present in both cytotrophoblast and syncytiotrophoblast, but it is synthesized mainly in the syncytiotrophoblast. The maternal circulating hCG concentration is approximately 100 IU/L at the time of the expected but missed menses. A maximal level of about 100,000 IU/L in the maternal circulation is reached at 8-10 weeks of gestation. There are two clinical conditions in which blood hCG titers are especially helpful: Trophoblastic disease and ectopic pregnancies. Trophoblastic disease is distinguished by very high b-hCG levels (3-100 times higher than normal pregnancy). Ectopic production of a-and b-hCG by non-trophoblastic tumours is rare, but does occur.

The Human placental lactogen (hPL) is secreted primarily into the maternal circulation, most of its functions occur at sites of action in maternal tissues. Human placental lactogen is thought to be responsible for the marked rise in maternal plasma insulin-like growth factor-1 (IGF-1) concentrations as the pregnancy approaches term. Human placental lactogen exerts metabolic effects during pregnancy, via IGF-I. It is associated with insulin resistance, enhances insulin secretion which stimulates lipolysis, increases circulating free fatty acids, and inhibits gluconeogenesis; in effect, it antagonizes insulin action, induces glucose intolerance, as well as lipolysis and proteolysis in the maternal system. Hence the role of universal screening for abnormal blood sugar in the beginning of the third trimester is emphasized in clinical practice.

In the fetus calcium concentrations, are regulated by the movement of calcium, across the placenta, from the maternal compartment. In order to maintain fetal bone growth, the maternal compartment undergoes adjustments that provide a net transfer of sufficient calcium to the fetus. Maternal compartment changes that permit calcium accumulation include increases in maternal dietary intake, increases in maternal D3 levels, and increases in parathyroid hormone levels.

Progesterone supplement in pregnancy: An immunologic therapy

There are several studies to understand the maintenance of pregnancy by progesterone. Progesterone has been shown to increase the cytokines produced by Th2 cells which predominate over those produced by Th1 cells, resulting in the maintenance of pregnancy. Th2 cells are dominant within the decidua in early pregnancy in humans. The Th2-derived cytokines, IL-4 and IL-6, induce the release of hCG from trophoblasts and the hCG stimulates progesterone production from corpus luteum in pregnancy. Progesterone has been shown to stimulate the secretion of Th2 and reduces the secretion of Th1 cytokines. Thus, maintenance of pregnancy has been attributed to Th2 type cytokine. This role in controlling the immune and endocrine system which promotes the function of the trophoblasts at the implantation site seems interesting.4 Use of progestogen in threatened abortion is controversial.5

Progesterone for recurrent miscarriage

Progestogen has been used for several years even before there was knowledge of the immunomodulatory properties of progesterone. Since that time, studies of differing quality have been carried out to prove the benefits of progestogen supplementation in affected women. A study on 146 women who presented with mild or moderate vaginal bleeding during the first trimester of pregnancy was randomized to receive oral dydrogesterone (10 mg b.i.d.) (n=86) or no treatment (n=60). Dydrogesterone was continued until 1 week after the bleeding had stopped. The incidence of miscarriage was significantly lower in the dydrogesterone group than in the untreated group (17.5% vs. 25%; P<0.05).6 The majority of cited clinical trials revealed a trend to improved pregnancies and increased live birth rates in the progestogen treatment group, but unfortunately, many studies had poor designs and methodical weaknesses.7 Several studies have shown that supportive care in early pregnancy is associated with a significant beneficial effect on pregnancy outcome. Women with otherwise unexplained recurrent pregnancy loss should be counselled regarding the potential for successful pregnancy without any treatment except supportive therapy such as folic acid or vitamin supplementation.7,8 The route of Progestogen administration are in various formulations, but it is generally recommend the exclusive use of progestogen without any (anti-) androgenic or (anti-) oestrogenic effect. Progestogen supplementation is available as vaginal suppositories (0.4 g/day, preferably in the evening because natural progesterone can cause tiredness), intramuscular injection (250 mg hydroxyprogesterone weekly) or oral intake (e.g. 10 mg dydrogesterone, the stereo-isomer of natural progesterone.9

Progesterone supplementation following assisted reproductive technology

The use of the progesterone supplementation in ART cycles has better clarity.10 The duration of progesterone supplementation following reproductive technology (ART) has been studied in a retrospective cohort study. One group had progesterone supplementation through the first trimester of pregnancy (first trimester protocol) till 12 weeks and the second group had the progesterone discontinued after a positive beta hCG test 2 weeks after retrieval (luteal protocol). A similar rate of clinical pregnancies occurred at 7 weeks (81.8% luteal protocol vs. 85.8% first trimester protocol) and for live birth rates (76.8% luteal protocol vs. 75.0% first trimester protocol). There was a trend toward a higher rate of pregnancy loss after 7 weeks in the first trimester protocol group occurred (15.5% vs. 4.4%), indicating that first trimester progesterone supplementation may support early pregnancy through 7 weeks by delaying miscarriage but does not improve live birth rates. There are randomized trials supporting the routine use of luteal support in ART cycles using GnRH agonists or antagonists. Fifty-nine studies were included in a review to evaluate the luteal phase support with hCG compared to placebo or no treatment, in terms of increased ongoing pregnancy rates. Luteal phase support with hCG or progesterone after assisted reproduction results in an increased pregnancy rate. HCG does not provide better results than progesterone, and is associated with a greater risk of OHSS when used with GnRHa. The optimal route of progesterone administration has not yet been established.11 A review showed a significant effect in favour of progesterone for luteal phase support, favouring synthetic progesterone over micronized progesterone.12

Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate

Preterm delivery should be anticipated and prevented to decrease perinatal morbidity and mortality. Those women who have had a spontaneous preterm delivery earlier are at greatly increased risk for preterm delivery in subsequent pregnancies. The results of several small trials have suggested that 17 alpha-hydroxyprogesterone caproate (17P) may reduce the risk of preterm delivery. A double-blind, placebo-controlled trial involving pregnant women with a documented history of spontaneous preterm delivery was done.13 A total of 19 clinical centers were taken for the study and pregnant women at 16 to 20 weeks of gestation were included and were randomly assigned by a central data center, in a 2:1 ratio, to receive either weekly injections of 250 mg of 17P or weekly injections of an inert oil placebo; injections were continued until delivery or to 36 weeks of gestation. Treatment with 17P significantly reduced the risk of delivery at less than 37 weeks of gestation which was 36.3 percent in the progesterone group vs. 54.9 percent in the placebo group; relative risk, delivery at less than 35 weeks of gestation was 20.6 percent vs. 30.7 percent; and delivery at less than 32 weeks of gestation was 11.4 percent vs. 19.6 percent. The incidence of necrotizing enterocolitis, intraventricular hemorrhage in infants of women treated with 17P had significantly lower rates of and need for supplemental oxygen. Hence, the study concluded that weekly injections of 17P resulted in a substantial reduction in the rate of recurrent preterm delivery among women who were at particularly high risk for preterm delivery and reduced the likelihood of several complications in their infants. One double blind randomized placebo controlled trials reported lower preterm birth rate with the use of either intramuscular 17 alpha-hydroxyprogesterone caproate (17P) or intravaginal micronized progesterone suppositories in women at risk for preterm delivery.14 The half-life of 17P was estimated to be approximately 7.8 days. The route of administration plays an important role in the drug’s safety and efficacy profile. Oral progesterone has not been used for prevention of preterm labor because of its first-pass hepatic metabolism, and there is a lack of data on efficacy, high side-effect profile, and because of extreme variability in plasma concentrations. Vaginal administration of progesterone avoids first-pass hepatic metabolism and is associated with rapid absorption, high bioavailability, and local endometrial effects.15 Vaginal route offers no local pain and few side effects, it is associated with variable blood concentrations.16 To study the efficacy of progesterone for maintenance tocolytic therapy after threatened preterm labor was done in a randomized controlled trial.17 The study was on 70 women who presented with symptoms of threatened preterm labor, who after arrest of uterine activity were then randomized to progesterone therapy or no treatment and the purpose of this study was to determine whether supplementation of vaginal progesterone after inhibition of preterm labor is associated with an increased latency period and a decreased recurrent of preterm labor. Treatment group received progesterone suppository (400 mg) daily until delivery and control group received no treatment. The study concluded that the use of vaginal progesterone suppository after successful parenteral tocolysis associated with a longer latency preceding delivery but failed to reduce the incidence of readmission for preterm labor. Dydrogesterone supplementation in women with threatened had preterm delivery the impact on cytokine profile, hormone profile, and progesterone-induced blocking factor.18

A study on eighty-three women with symptoms of threatened preterm birth were either randomized to study groups receiving tocolytic treatment combined with intravaginal micronized natural progesterone (200 mg daily) or to a control group receiving only tocolysis. Micronized natural progesterone treatment resulted in a prolonged latency period of 32.1±17.8 versus 21.2±16.3 days in the control group and heavier birth weights of 2,982.8±697.8 g versus 2,585.3±746.6 g.19

Estradiol supplementation during the luteal phase of in vitro fertilization cycles

A prospective randomized study was done to find the optimal dosage of estradiol (E2) for luteal phase support through the addition of different doses of E2 to progesterone (P) luteal phase support in patients undergoing long GnRH agonist in vitro fertilization (IVF) treatments.20 Two hundred and eighty-five women undergoing IVF treatment with a long GnRH agonist protocol were prospectively randomized into three groups. Group 1 (n=95) received P and 2 mg E2, group 2 (n=95) received P and 4 mg E2 and group 3 (n=95) received P and 6 mg E2 as luteal phase support. The primary outcome was the clinical pregnancy rate (PR). The secondary variables of interest were the implantation rate (IR), miscarriage rate and multiple PR. The clinical PR was 31.6%, 40% and 32% respectively in groups 1, 2 and 3 and the differences between groups were not statistically significant. However, the miscarriage rate was significantly lower in group 2 (2.6%) than in group 1 (20%) but was not significantly lower than in group 3 (9.6%). The study concluded that the in luteal phase adding 2, 4 or 6 mg of oral E2 to P creates no statistical difference in terms of pregnancy rates. However, a significantly higher miscarriage rate was found when 2 mg E2 was used. Therefore, in the luteal phase support, 4 mg of oral estradiol in addition to progesterone can be considered to reduce the miscarriage rate. More research is still required on identification of at risk group, the optimal gestational age at initiation, mode of administration, dose of progesterone and long-term safety.

Thyroid disorders

This has a great impact on fertility. Sex hormone-binding globulin (SHBG) is altered with hyperthyroidism and hypothyroidism. It also changes prolactin, gonadotropin-releasing hormone, and sex steroid serum levels. It may also have a direct effect on oocytes, because it is known that specific binding sites for thyroxin are found on mouse and human oocytes. There is also an association between thyroid dysfunction in women and morbidity and outcome in pregnancy. In males, hyperthyroidism causes a reduction in sperm motility. The numbers of morphologically abnormal sperm are increased by hypothyroidism. It has been found that when euthyroidism is restored, both abnormalities improve or normalize. In women, the alterations in fertility caused by thyroid disorders are more complex. Hyper- and hypothyroidism are the main thyroid diseases that have an adverse effect on female reproduction and cause menstrual disturbances-mainly hypomenorrhea and polymenorrhea in hyperthyroidism, and oligomenorrhea in hypothyroidism. All factors may be connected to the alterations in the metabolic pathway. Adequate levels of circulating thyroid hormones are of primary importance for normal reproductive function.21

Controlled ovarian hyperstimulation leads to increases in estradiol, which in turn may have an adverse effect on thyroid hormones and TSH. Ovarian hyperstimulation may become severe when autoimmune thyroid disease is present, depending on preexisting thyroid abnormalities. Autoimmune thyroid disease is present in 5-20% of unselected pregnant women. Isolated hypothyroxinemia has been described in approximately 2% of pregnancies, without serum TSH elevation and in the absence of thyroid auto antibodies. There is an association of increased rates of spontaneous abortion, premature delivery and/or low birth weight, fetal distress in labor, and perhaps gestation-induced hypertension and placental abruption in overt hypothyroidism. All antithyroid drugs cross the placenta and may potentially affect fetal thyroid function.22

Thyroid disorders are common in women during pregnancy. If left untreated, both hypothyroidism and hyperthyroidism are associated with adverse effects on pregnancy and fetal outcomes. It is important to correctly identify these disorders and treat them appropriately to prevent pregnancy-related complications. Indicated treatment is Levothyroxine for hypothyroidism, and thioamides are the treatment of choice for hyperthyroidism; thyroidectomy may be indicated in select cases.23,24 Cochrane review of three RCTs involving 314 women showed in one trial of 115 women, levothyroxine therapy to treat pregnant euthyroid women with thyroid peroxidase antibodies was not shown to reduce pre-eclampsia but did significantly reduce preterm birth by 72%. One trial of 30 hypothyroid women compared levothyroxine doses, but only reported biochemical outcomes. A trial of 169 women compared the trace element selenomethionine (selenium) with placebo and no significant differences were seen for either pre-eclampsia or preterm birth. None of the three trials reported on childhood neurodevelopmental delay.25

Medical treatment for menorrhagia may only delay hysterectomy

Dear Editor:

In response to Dr. Ellen Grant’s excellent comments about natural
progesterone cream, I want to warn others about this popular, so-called
“safe” product.

My initial suffering from fatigue, weight gain, and depression were
brought on by the Pill, which I took during the first year I was married.

Oral contraceptives also caused my thyroid to malfunction, and I
developed hypothyroidism.

What I didn’t know until much later was that often the ill-effects of
the
Pill on brain chemistry and metabolism ~ not to mention a myriad of
other bodily systems ~ can be chronic even after ceasing usage. I knew
something dramatic had changed, because I had not had health
problems earlier in life.

I had been constantly researching, trying to find ways of returning
to
real wellness. Unfortunately, I ran across the wrong book…Dr. John
Lee’s ‘What Your Doctor May Not Tell You About Pre-Menopause.’ The
consequences of his advice were devastating.

On his recommendations, I used natural progesterone cream. Dr. Lee
claimed that it is impossible to overdose on the transdermal cream, and
that there are no significant side effects. At first, I believed him.

Following the manufacturer’s information and instructions, the amount

of progesterone I used per day was between 20-30mg, split between
morning and evening doses. When I first took the cream, beginning in
May 2003, I felt great. In fact, I had more energy and ability to lose
weight than I had in about five years. I didn’t need near as much sleep,
and found that I no longer struggled with depression.

However…

Within about two months of starting the cream, I developed sharp pain

in my legs, and then a lump of swelling, bruising, and localized soreness
in my calf which just got worse. That ended up being the first of two
episodes with venous blood clots in the six months I was on the cream.
Little did I know that progesterone is heavily implicated in clotting
disorders, much as the Pill is. Not one of my doctors ever made the
connection between my blood clots and the progesterone.

We also noticed that my “resting” heart rate was going through the
roof.
One day when I had been on the cream about two months, we stopped
at a blood pressure machine, and my heart rate (while wandering
aimlessly around a store) was over 120! There were several times when
my heart felt like it was pounding out of my chest. I kept putting this
down to thyroid trouble. As a doctor in LA told me later, “Yes, no
wonder you were losing weight…at the expense of your heart!”

Something else that got my attention was that I started to become
emotional in a way that I had never been in my life. Even though I wasn’t

feeling overtly depressed (that I was aware of), I would burst out crying
at the strangest times, and a lot more frequently than ever before. I
started feeling overwhelmed and annoyed by things that used to be no
big deal. My temper got shorter with the kids and with my husband.
This feeling crept up on me a little at a time, but it began to get worse
and worse. I now realize, from extensive reading about the actions of
progesterone, that this is typical for a large segment of those using
hormones.

By August 2003, I knew something was really “wrong,” but I couldn’t
put
my finger on it. I had this feeling of unease that was growing and
growing. A pattern started where, during the week before my period
and often the week of, I would become extremely nauseous. For several
months, we were sure I was pregnant. I never was.

At the beginning of October 2003, something in my body “snapped” and
the nausea took hold in a frightening way. If I had known then that it
would last ~ without relief, for months straight ~ I don’t know if I could

have borne it.

When I couldn’t stop throwing up and couldn’t eat and it had been
three
weeks – that was when I ran across the first doctor who said, “Well, if
there’s one thing I know that makes pregnant women sick as dogs, it’s
progesterone. I’d look there first, if you want to know why you can’t
stop vomiting.” I quit the cream on October 26, 2003.

The bad news, which I got soon after, was that progesterone cream
builds up in the tissues and takes anywhere from three to six months to
be cleared by the body. This timeline ended up being almost exactly
true for me. I was sick, sick, sick until about two weeks ago.

The symptoms during those six months of illness as I rebounded from
the cream are almost too many to list, but they include: severe nausea
and vomiting, gastro-intestinal problems (marked heartburn, bouts of
diarrhea, and bouts of constipation), uncontrollable shaking, acne and
extremely oily skin, hirtuism, depression, anxiety, tingling/burning
sensations on the back of my arms, neck, and head, insomnia, hyper-
sensitivity to medications and foods, hot flashes, and serious withdrawal
symptoms. To my great relief, most all of these issues have finally,
completely resolved. Today, only the insomnia remains.

It turns out that *lots* of people are having trouble with natural
progesterone cream. A hormone researcher confirmed that my
symptoms were quite consistent with excess progesterone.

On his web site, Dr. Mark Rhodes writes:

“Many people overdose from prolonged use of progesterone cream. It is

promoted so heavily, so easily available, so inexpensive, and so readily
absorbed. The real problem is several-fold in my opinion. It is difficult
to
get an exact individual dose. Because it does relieve a number of
symptoms of estrogen dominance, I am sure that some use more than
they should. But the most insidious problem comes from long-term use.
Many women who use a topical progesterone product end up having it
accumulate in their tissues. It then can release into the blood stream at
very high levels . And we see this high-level release occur for months
after the patient quits application…”

Information about other doctors experiencing problems in
patients taking progesterone cream available at:

http://www.mercola.com/article/progesterone/cream.htm

Neither blood serum nor saliva tests are accurately revealing the
high
levels of progesterone that the creams can cause. Many women – and
I’m one of them – show up in these tests as having LOW progesterone
levels even when their bodies have become toxic due to overdose! This
really threw my doctors off the trail. They wanted to put me back
ON progesterone, but thankfully I was never willing.

Lots of researchers seem to be catching on to the fact that natural
progesterone can be anything but harmless. The following information
was released last week by the American Society of Clinical
Pharmacologists:

http://ascpt.org/press/2004/2004NewResearch.htm

I realize this letter is long, but if one woman is spared the misery
I
endured, it will be worth sharing what happened. I hope that more and
more people will seriously reconsider their advocacy and use of
hormones, whether “natural” or not.

Cathy Groves

Competing interests:
“Natural” Progesterone
Cream nearly killed
me!

Fertility and menstruation are largely controlled by hormones, and one of these hormones is progesterone. Progesterone is a steroid hormone belonging to a class of hormones called progestogens. It is secreted by the corpus luteum, a temporary endocrine gland that the female body produces after ovulation during the second half of the menstrual cycle.

Synthetic steroid hormones with progesterone-like properties are called progestins. Progestin is often combined with estrogen, another hormone, to develop contraceptives such as birth control pills and skin patches. Progestin is also useful in treating common menopausal symptoms. Understanding progesterone and progestins will help women make informed choices about their reproductive health.

What Does Progesterone Do?

Progesterone prepares the endometrium for the potential of pregnancy after ovulation. It triggers the lining to thicken to accept a fertilized egg. It also prohibits the muscle contractions in the uterus that would cause the body to reject an egg. While the body is producing high levels of progesterone, the body will not ovulate.

If the woman does not become pregnant, the corpus luteum breaks down, lowering the progesterone levels in the body. This change sparks menstruation. If the body does conceive, progesterone continues to stimulate the body to provide the blood vessels in the endometrium that will feed the growing fetus. The hormone also prepares the limit of the uterus further so it can accept the fertilized egg.

Once the placenta develops, it also begins to secrete progesterone, supporting the corpus luteum. This causes the levels to remain elevated throughout the pregnancy, so the body does not produce more eggs. It also helps prepare the breasts for milk production.

What Does Progestin Do?

Progestins were created to bind to progesterone receptors in the body and create similar effects as progesterone. Progestin can change the lining of the uterus and stop the lining from building up. Scientists made progestin because progesterone isn’t absorbed well when taken as a pill.

Progestin can also be used to treat menopause symptoms such as hot flashes and vaginal dryness. Estrogen can be used alone to treat these symptoms, or it can be combined with progestin.For women who are perimenopausal or newly menopausal, healthcare providers may suggest an oral micronized progesterone treatment.

Progestin can also be prescribed to treat amenorrhea, endometriosis, and irregular periods.

Potential Problems with Progesterone Production

Women who have low levels of progesterone will have abnormal menstrual cycles or may struggle to conceive because the progesterone does not trigger the proper environment for a conceived egg to grow. Women who have low progesterone levels and who do succeed in getting pregnant are at higher risk for miscarriage or pre-term delivery, because the hormone helps maintain the pregnancy.

Signs of low progesterone include:

  • Abnormal uterine bleeding
  • Irregular or missed periods
  • Spotting and abdominal pain during pregnancy
  • Frequent miscarriages

In addition, low progesterone levels can cause too-high levels of estrogen, which can decrease sex drive, contribute to weight gain, or cause gallbladder problems.

What Problems Can Occur with Progestin?

Women who have low levels of progesterone will have abnormal menstrual cycles or may struggle to conceive because the progesterone does not trigger the proper environment for a conceived egg to grow. Women who have low progesterone levels and who do succeed in getting pregnant are at higher risk for miscarriage or pre-term delivery, because the hormone helps maintain the pregnancy.

If you are taking progestin to treat menopausal symptoms, for birth control, or to treat other conditions side effects may occur. Side effects may occur due to the dosage of progestin, how progestin interacts with hormone receptors, and your body’s response to progestin.

When taking progestin for menopausal symptoms, side effects may include mood changes, bloating, headaches, and breast tenderness. For newly menopausal women, breakthrough bleeding may occur.

In hormonal birth control, progestin side effects can include withdrawal bleeding and increased cramping. Other side effects may include an increased blood pressure and low blood sugar.

Questions to Ask Your Healthcare Team

For women who are struggling to conceive or carry a pregnancy, the emotional toll of the struggle is high. While you need to pursue every potential cause of this problem, it’s valuable to talk to your doctor about your progesterone levels. If this is the problem, treatment is not difficult, but you should talk to your doctor before starting supplementation. Consider asking these questions:

  • How can I determine if I am suffering from low progesterone levels?
  • What other conditions could be causing my symptoms?
  • How can I treat low progesterone levels?
  • If I take supplemental progesterone, how long should I take it or when should I stop taking it?
  • Am I a candidate for menopausal treatment therapy?
  • Am I at risk for any side effects?
  • Which hormonal birth control method should I use?

Prometrium

SIDE EFFECTS

See BOX WARNING, WARNINGS and PRECAUTIONS.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

In a multicenter, randomized, double-blind, placebo-controlled clinical trial, the effects of PROMETRIUM Capsules on the endometrium was studied in a total of 875 postmenopausal women. Table 6 lists adverse reactions greater than or equal to 2 percent of women who received cyclic PROMETRIUM Capsules 200 mg daily (12 days per calendar month cycle) with 0.625 mg conjugated estrogens or placebo.

TABLE 6. Adverse Reactions (≥ 2%) Reported in an 875 Patient Placebo-Controlled Trial in Postmenopausal Women Over a 3-Year Period

PROMETRIUM Capsules 200 mg with Conjugated Estrogens 0.625 mg Placebo
(n=178) (n=174)
Headache 31 27
Breast T enderness 27 6
Joint Pain 20 29
Depression 19 12
Dizziness 15 9
Abd! minal Bloating 12 5
HogT’lashes 11 35
Urinary Problems 11 9
Abdominal Pain 10 10
Vaginal Discharge 10 3
Nausea / Vomiting 8 7
Worry 8 4
Chest Pain 7 5
Diarrhea 7 4
Night Sweats 7 17
Breast Pain 6 2
Swelling of Hands and Feet 6 9
Vaginal Dryness 6 10
Constipation 3 2
Breast Carcinoma 2 <1
Breast Excisional Biopsy 2 <1
Cholecystectomy 2 <1

Effects On Secondary Amenorrhea

In a multicenter, randomized, double-blind, placebo-controlled clinical trial, the effects of PROMETRIUM Capsules on secondary amenorrhea was studied in 49 estrogen-primed postmenopausal women. Table 7 lists adverse reactions greater than or equal to 5 percent of women who received PROMETRIUM Capsules or placebo.

TABLE 7. Adverse Reactions (≥ 5%) Reported in Patients Using 400 mg/day in a Placebo- Controlled Trial in Estrogen-Primed Postmenopausal Women

Adverse Experience PROMETRIUM Capsules 400 mg Placebo
n=25 n=24
Percentage (%) of Patients
Fatigue 8 4
Headache 16 8
Dizziness 24 4
Abdominal Distention (Bloating) 8 8
Abdominal Pain (Cramping) 20 13
Diarrhea 8 4
Nausea 8 0
Back Pain 8 8
Musculoskeletal Pain 12 4
Irritability 8 4
Breast Pain 16 8
Infection Viral 12 0
Coughing 8 0

In a multicenter, parallel-group, open label postmarketing dosing study consisting of three consecutive 28-day treatment cycles, 220 premenopausal women with secondary amenorrhea were randomized to receive daily conjugated estrogens therapy (0.625 mg conjugated estrogens) and PROMETRIUM Capsules, 300 mg per day (n=113) or PROMETRIUM Capsules, 400 mg per /day (n=107) for 10 days of each treatment cycle. Overall, the most frequently reported treatment-emergent adverse reactions, reported in greater than or equal to 5 percent of subjects, were nausea, fatigue, vaginal mycosis, nasopharyngitis, upper respiratory tract infection, headache, dizziness, breast tenderness, abdominal distension, acne, dysmenorrhea, mood swing, and urinary tract infection.

Postmarketing Experience

The following additional adverse reactions have been reported with PROMETRIUM Capsules. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate the frequency or establish a causal relationship to drug exposure.

Genitourinary System

endometrial carcinoma, hypospadia, intra-uterine death, menorrhagia, menstrual disorder, metrorrhagia, ovarian cyst, spontaneous abortion.

Cardiovascular

circulatory collapse, congenital heart disease (including ventricular septal defect and patent ductus arteriosus), hypertension, hypotension, tachycardia.

Gastrointestinal

acute pancreatitis, cholestasis, cholestatic hepatitis, dysphagia, hepatic failure, hepatic necrosis, hepatitis, increased liver function tests (including alanine aminotransferase increased, aspartate aminotransferase increased, gamma-glutamyl transferase increased), jaundice, swollen tongue.

Skin

alopecia, pruritus, urticaria.

Eyes

blurred vision, diplopia, visual disturbance.

Central Nervous System

aggression, convulsion, depersonalization, depressed consciousness, disorientation, dysarthria, loss of consciousness, paresthesia, sedation, stupor, syncope (with and without hypotension), transient ischemic attack, suicidal ideation.

During initial therapy, a few women have experienced a constellation of many or all of the following symptoms: extreme dizziness and/or drowsiness, blurred vision, slurred speech, difficulty walking, loss of consciousness, vertigo, confusion, disorientation, feeling drunk, and shortness of breath.

Miscellaneous

abnormal gait, anaphylactic reaction, arthralgia, blood glucose increased, choking, cleft lip, cleft palate, difficulty walking, dyspnea, face edema, feeling abnormal, feeling drunk, hypersensitivity, asthma, muscle cramp, throat tightness, tinnitus, vertigo, weight decreased, weight increased.

Read the entire FDA prescribing information for Prometrium (Progesterone)

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