Every pregnancy depends on progesterone. Progesterone is one of the most important conditions in the process that leads to the union of the very small embryo with the uterine wall. Progesterone helps the embryonic egg form the placenta, which will provide nourishment for the fetus for nine months. Natural progesterone, or endogenous progesterone (produced in your own body), is produced in the corpus luteum, the ovary from which the egg sprouts. After about the 4th week of pregnancy, the secretory functions of the ovaries and corpus luteum begin to be replaced by the placenta in order to ensure that the pregnancy proceeds normally. Gradually, the fetal placenta produces sufficient progesterone to take over from the ovaries to ensure that the pregnancy requires progesterone. Theoretically, by the eighth week of pregnancy, the amount of progesterone produced by the placenta has made the role of the ovaries as the hormone-producing organ less important.
Historically, doctors have given pregnant women exogenous progesterone (progesterone that originates outside our bodies) for two reasons.
(1) to avoid “early abortions”;
(2) to maintain a normal growth environment for the implantation of donor eggs, which has only been commonly practiced in recent years. Taking progesterone to avoid miscarriage is now an outdated practice. However, it is customary for doctors to give progesterone to pregnant women receiving egg implants during the first 8 weeks to the first 16 weeks of pregnancy to “help the pregnancy succeed”. Pregnant women who receive eggs are completely dependent on exogenous progesterone in the early stages of pregnancy to ensure a normal environment for the fetus to survive, as these women do not have a corpus luteum to produce this hormone. (It is the egg donor – not the egg recipient – that ovulates and produces the corpus luteum.)
The benefits of using exogenous progesterone in egg recipients are obvious, since the purpose of progesterone in this type of pregnancy is to make the pregnancy successful. But how much progesterone is most appropriate for this type of pregnancy – and for how long can it be used? The doctor’s answer to the second question can be a matter of opinion and wisdom. Some doctors prescribe progesterone for 10 weeks, others for 12 weeks, and still others for 16 weeks.
12 weeks of progesterone therapy is more reasonable (compared to 16 weeks). By that time the placenta is already functioning. You can stop taking progesterone at 8 weeks. Progesterone (as a therapeutic drug) does not do much after week 8. Dr. Alan Killam expresses his opinion based on the normal physiological hormonal changes of pregnancy, that generally after the 8th week of pregnancy, the corpus luteum no longer produces most of the hormones on which the embryo depends.
”After the eighth week, if you remove the ovaries, the fetus grows as usual.” Killam says, “I don’t think it’s necessary to give progesterone after 12 weeks.” According to Killam, progesterone is needed early in pregnancy, but in the second trimester, you will produce enough progesterone that if you take progesterone at that point, you are definitely overdosing.
However, many doctors, to be on the safe side, will recommend that egg recipients take progesterone for 12 to 16 weeks. Their reasoning is understandable: highly technically grown babies are hard to come by (and expensive to build), so doctors will do everything they can to ensure the success of such pregnancies.
The problem is that we have to consider the side effects of the drugs on the fetus, so we have to ask, is this practice really safe? The reason this question is raised as a very important one is that every year we have thousands of pregnant women – women who have ovulatory dysfunction, women who are afraid of miscarriage, and women who have had to go through high tech means to conceive – -are taking this exogenous progesterone.
Because the vast majority of progesterone’s composition conforms to its “natural form,” many doctors consider these hormonal drugs to be safe. Dr. Mark Suhr, who uses progesterone at his Columbia University hospital, believes it has few side effects: “You’re giving them the first 12 to 14 weeks of their pregnancy to supplement their progesterone deficit. Your body produces so much progesterone that it can make the hormone you’re giving ineffective. We use are tiny vaginal gel suppositories that have very few side effects. The progesterone can go directly into the pelvic vessels: it can be absorbed directly.” Gideon Koren, professor of medical genetics and pediatrics and head of the Maternal Risk Program, also believes progesterone is safe because in 20 years he hasn’t encountered a case of progesterone causing abnormal development in a child.
But at the same time, there are those who disagree with this view. Some biologists and toxicologists specialize in studying the effects of progesterone on the “growing tissue” – the fetus. Dr. Lovell Jones, a research scientist in the Medical Division of the Anderson Cancer Institute and chief of the Division of Experimental Gynecology I Endocrinology, is concerned about the safety of the fetus in utero under the influence of exogenous progesterone. In the mid-term, Jones found from experimental studies of the fetal response to the effects of small doses of the drug in mice that progesterone administration to pregnant mice can cause reproductive abnormalities in infant mice. Therefore, Jones felt that further research should be done on this topic before administering progesterone to pregnant women.
Once again, the question comes back to whether progesterone gives a person a benefit or a danger. The benefits of the drug to the egg recipient are obvious; without progesterone there would be no child. But does the use of progesterone also have a positive effect on other conditions – luteal hypofunction and early miscarriage? The disagreement on this question is significant.
While there is solid evidence that progesterone has a nurturing effect on donor egg pregnancies, it is unclear whether progesterone also has a therapeutic effect on hypoplasticity and early miscarriage. Therefore, the effectiveness of using progesterone for both conditions remains controversial.
A prospective double-blind randomized trial (the most reliable clinical trial method) conducted in the 1970s showed that progesterone did not prevent miscarriage, a conclusion made by Alan Killam. In the 1960s, it was widely believed that progesterone had a role in preventing miscarriages. The results of the study were promising – until the trial allowed the use of a placebo. When placebos were used in randomized double-blind experimental studies, it was shown that progesterone did not have this effect. By the 1970s, progesterone was banned for the treatment of miscarriages.
According to Dr. Murray Engin and his co-authors, “Guidelines for the Care of Pregnancy and Childbirth” (2nd edition), several randomized studies of progesterone in early pregnancy have shown no evidence that progesterone reduces the risk of miscarriage, stillbirth, or neonatal death in women with vaginal bleeding or habitual abortion. However, these studies have not gone so far as to rule out one of the two effects (increased or decreased miscarriage).
Some doctors also believe that progesterone can prevent miscarriages and so continue to prescribe this medication to pregnant women. As for how to treat luteal hypofunction, Killam says, “The medical community is divided.” Fifty percent of obstetricians don’t even acknowledge the existence of hypolipidemia, arguing that even if it exists, it is nothing more than an exaggerated claim.
Other physicians disagreed with this view. They argue that most cases of miscarriage indicate that this is a natural way to eliminate a genetically defective fetus, so progesterone should not be used to stop it. high rates of miscarriage in women over 35 are due to congenital genetic defects in the egg or fertilized egg – conditions that progesterone therapy cannot address.
Ellen Killam believes progesterone may occasionally have a placebo effect. A placebo works when the patient feels “better” (in this case, stays pregnant) after taking the drug, when there is no relationship between the drug she is taking and the drug that actually cures her condition. The placebo (a “sugar pill” with no real drug component) improved the condition partly because the patient had confidence in the doctor, and partly because the patient had the psychological implication that she was being treated. Dr. Killam hypothesized that the efficacy of progesterone in preventing miscarriage may be achieved by reducing stress levels and increasing maternal confidence.
Ironically, some pregnancy medications cause luteal hypofunction (manifested by lower progesterone levels) and as a result, embryos have difficulty implanting in the uterus, thus reducing the chances of pregnancy. “Hypo-luteal disease can occur with the use of in vitro fertilization (IVF) drugs.” Dr. Mark Suhr said. He explains the awkward situation faced by women undergoing fertility treatment: the drugs used to treat infertility cause you to ovulate, but the expelled eggs are stunted and do not automatically produce progesterone, so you need the drugs to help you replenish it. In this way, your doctor may prescribe you progesterone in order to “treat” the pregnancy symptoms caused by the pregnancy medication. The scientific debate – is there a long-term threat to the fetus?
Is the benefit we receive worth the possible long-term risk?
The types of progesterone drugs currently in use and their dosages are safe for pregnant women. They believe that the progesterone given is intended to help the fetus get the “natural amount of hormone” that it needs, which is present during pregnancy and is consistent with the physiological levels of hormones that a pregnant woman should have under normal circumstances.
The progesterone given to the fetus before birth is natural, yet exogenous. Whether this causes long-term adverse side effects is not known at this time, as it is unethical to conduct clinical drug trials on pregnant women. However, many doctors think it is unlikely that progesterone causes long-term side effects because the drug has been used for generations and they have not found any problems.
But on the other hand, many of the developmental biologists and oncology researchers interviewed for this book say that we have not studied the drug extensively enough to know if it is not harmful to a growing fetus. These scientists cite the results of animal studies as an example. They say that natural forms of progesterone given exogenously to pregnant animals during pregnancy can cause abnormalities; that because the hormone drug is “natural,” it is considered harmless is debatable.
According to Dr. Lovell, Jones, the fact that progesterone is not harmful to adults does not mean that it is safe for the fragile, growing fetus. We talk about drugs or compounds that have no side effects on people, but we must always remember that the fetus is not a small adult. Drugs that are safe for adults to take may not be safe for fetuses to be exposed to. Jones wants pregnant women to learn this for themselves and to learn to choose their pregnancy medications wisely.
What we know should make us more cautious. Data from animal tests tell us that if you are pregnant, there is a risk of harmful effects of use on the next generation. This danger is hidden. Of course this opinion is not conclusive, but the possibility is there. It’s your choice, and it should be a sober one.
Researchers like Dr. Howard Born, Dr. Lovell Jones and Dr. Richard Hajack are particularly concerned about fetal exposure to therapeutic progesterone during the first 6 to 9 weeks of gestation – the first 3 months of pregnancy. The scientists’ concerns are based on the results of animal studies, as there is no precedent to date for testing on humans, primarily considering the effects of progesterone with the fetus. However, female pups exposed to the drug – the equivalent of a human fetus at the growth stage of 6 to 9 months – were born with abnormal reproductive organ development. According to Dr. Hajjak’s research, the most typical abnormalities in animals include keratinization of the vaginal mucosa and ectopic endometrium to the vagina (an abnormality that also occurs in daughters born to women who have taken hexestrol). o Some researchers are concerned that those fetuses exposed to progesterone may also have abnormalities of the reproductive duct, although these abnormalities are not readily observable until they reach adulthood.
Yet many physicians do not share these concerns because they have never seen a case of a child born to a woman who had used progesterone who developed abnormal reproductive organs during their adolescence or adulthood. Other doctors treat this problem as unsolvable. Dr. Murray Engin and his co-authors in his Guide to Care in Pregnancy and Childbirth (3rd edition) point out that because such experiments have not been performed in humans to date, it is not known whether progesterone (progesterone) is safe for infants or not. Although follow-up studies of women who have used progesterone are mostly uncontrolled and anecdotal, some of the recommendations made in the studies are worth noting: progesterone-affected fetuses have an increased probability of heart, nerve, and neuraxial canal disease, other tissue dysplasia and other conditions, as well as masculinization of the female fetus’ genitalia and a girl who is a “tomboy. “The study also showed that the fetus had a higher risk of heart, neurological, and neuraxial vascular disease. Other studies have not shown these adverse effects, so concluding that the safety of progesterone is as open a topic as the benefits progesterone has been found to have.