Estrogen During Pregnancy: Exploring The Safety Debate

Estrogen and progesterone are critical hormones for the normal development of the endometrial lining of the uterus. They are frequently used in patients undergoing a frozen embryo transfer (FET) or donor-egg IVF. Estrogen thickens the lining and then progesterone causes the lining to mature, ultimately allowing for the embryo's implantation. While these hormones are essential for a healthy pregnancy, there are some concerns about the safety of taking them as supplements.

In the 1950s and 1960s, a synthetic form of estrogen called diethylstilbestrol (DES) was given to women who were threatening to miscarry. Unfortunately, DES interfered with the normal functioning of estrogen receptors in the cells of the developing female reproductive tract in the unborn daughters of mothers who were prescribed the drug. As a result, many of those women were found to have significant reproductive tract abnormalities and were at a higher risk for an unusual form of vaginal cancer called clear cell carcinoma. This led to DES being taken off the market.

A study investigating the use of female sex hormones during pregnancy and their potential link to maternal and childhood cancers and genital malformations found that while there was no increased risk of cancer, there was a higher number of malformations recorded among exposed children. Another study in animals found that high doses of synthetic estrogens led to urogenital malformations in the offspring, although the relevance of these findings to humans is uncertain.

In summary, while estrogen and progesterone are crucial hormones for pregnancy, the use of synthetic forms or supplements should be carefully considered and discussed with a healthcare provider, as there may be potential risks associated with their use.

Estrogen and progesterone are critical hormones for the normal development of the endometrial lining of the uterus

Estrogen and progesterone are both steroid hormones that play a critical role in the menstrual cycle and the development of the endometrial lining of the uterus. Estrogen is responsible for the proliferation of the endometrial lining, while progesterone causes the lining to mature, ultimately allowing for the embryo's implantation. Estrogen is produced by the ovaries and the placenta during pregnancy, while progesterone is produced by the ovaries, the placenta, and the adrenal glands.

Estrogen can be prescribed to prevent miscarriage

Estrogen and progesterone are hormones that play a critical role in maintaining pregnancy. They prepare the uterine lining for the implantation of a fertilized egg, and progesterone also prevents muscle contractions in the uterus that could cause the body to reject an implanted egg.

Historically, both hormones were used to prevent threatened pregnancies. In the 1940s, it was believed that combining them would be more effective, leading to the use of estrogen and progesterone to prevent miscarriage. However, there is insufficient evidence to determine the efficacy of this treatment.

A review of randomised controlled trials found only two trials that met the inclusion criteria, and these involved small numbers of women. The first trial, involving 161 women with diabetes, showed no significant difference in the rate of miscarriage between the group that took oral estrogen and progesterone and the group that took a placebo. The second trial, involving 120 women who had undergone in-vitro fertilisation, also showed no difference in the rate of miscarriage between the group that took estrogen and progesterone and the group that received no treatment.

While these trials did not show that estrogen and progesterone can prevent miscarriage, it is important to note that they involved small sample sizes, and further research is needed to reach a definitive conclusion.

It is worth mentioning that estrogen was previously prescribed to prevent miscarriage in the 1940s to 1970s in the form of a synthetic estrogen called diethylstilbestrol (DES). However, this practice was discontinued after it was linked to an increased risk of reproductive tract abnormalities and a rare form of vaginal cancer in the daughters of women who took DES during pregnancy.

Animal studies have shown that high doses of estrogen can cause urogenital malformations in offspring

In a study of 2,052 hormone-exposed mothers, 2,038 control mothers, and their 4,130 infants, there was a significantly increased risk of cryptorchidism but not hypospadias in sons of women working in gardening. The total number of malformations recorded, as well as malformations of the genitals in male infants, were higher among exposed children.

In another study, pregnant mice were exposed to varying doses of either E2 or the synthetic estrogen diethylstilbestrol, and the prostates of adult male mice were analysed. The results revealed that small elevations in E2 exposure in utero led to an increase in the enlargement and in the expression of the androgen receptor in the prostate. Interestingly, higher doses of E2 in utero did not lead to an increased exacerbation of these phenotypes in adult male mice, thus generating a nonmonotonic dose–response curve, such that low doses of E2 were stimulatory, and high doses were inhibitory.

In a separate study, the effects of low-dose estrogen on gene expression in fetal mouse prostate mesenchyme in primary culture were examined. The concentration of estradiol chosen was 100 nM, and that of BPA was 10-fold higher (1000 nM), since BPA is less potent than estradiol. The results obtained for cells treated with estradiol were consistent with the microarray expression profiles. The data obtained for cells treated with BPA mostly showed similarities, but not in every case. Whereas AR, Esr1, Cyp7b1 and Sfrp4 were similarly up-regulated and Capn6 was similarly down-regulated by estradiol and BPA, Thbs2 activity was not induced and Bmp4 expression was not inhibited by BPA treatment.

Estrogen supplements come in the form of patches and pills

Estrogen supplements are available in a few different forms, including patches and pills. Intramuscular injections of estrogen can also be prescribed, but this is much less common.

If you are given patches, make sure you understand how many patches to apply and how often you should change them. Generally, patches can be applied anywhere you are comfortable, although some sources suggest applying them to the lower stomach area, below the waistline. Check with your healthcare provider to see if they prefer a particular site for the patch to be applied.

If you are taking pills, follow your doctor's instructions for dosing. Most estrogen pills are taken once a day without food. Some have more complicated dosing schedules.

The pros of taking estrogen pills are that they can reduce or resolve menopause symptoms and lower the risk of osteoporosis. They are also the best-studied type of estrogen therapy. However, the risks of this type of therapy have been well-publicized. On its own, estrogen causes a slight increase in the risk of strokes, blood clots, and other problems. When combined with the hormone progestin, the risks of breast cancer and heart attack may rise as well. Oral estrogen can also be hard on the liver, so people with liver damage should not take it.

The pros of taking estrogen patches are that they offer the same benefits as oral therapy, plus additional advantages. For example, the patch is more convenient than taking a pill each day. Patches are also safer for people with liver problems because the estrogen bypasses the liver and goes directly into the blood. According to studies, women who used oral estrogen therapy were 58% more likely to develop a blood clot within 90 days than those who did not. Women who used estrogen patches did not have an increased risk of blood clots. However, it's important to note that estrogen patches pose most of the same risks as pills, including a very small increase in the risk of serious problems like cancer and stroke. They also have similar side effects, including painful and swollen breasts, vaginal discharge, headaches, and nausea.

Hormone supplements are safe to take in early pregnancy when prescribed by a healthcare provider experienced in treating women with hormonal problems

It is important to note that, in general, dietary and herbal supplements are not recommended during pregnancy. Unlike prescription drugs, dietary supplements are not reviewed by the U.S. Food and Drug Administration (FDA) for safety and effectiveness. As such, they may contain contaminants like metals, pesticides, chemicals, or bacteria, which may be risky for pregnant women.

However, hormone supplements, such as estrogen and progesterone, are safe to take in early pregnancy when prescribed by a healthcare provider experienced in treating women with hormonal problems. These hormones are typically prescribed to prevent miscarriage in women with certain conditions, such as recurrent miscarriages. They are also commonly used in infertility treatments, including in vitro fertilization, frozen embryo transfers, and donor egg cycles.

Estrogen and progesterone are critical for the normal development of the endometrial lining of the uterus. Estrogen helps thicken the uterine lining, while progesterone causes it to mature, allowing for the embryo's implantation. These hormones are also essential for fetal growth and development.

If you are prescribed hormone supplements during early pregnancy, be sure to follow your healthcare provider's instructions for dosage and administration. Additionally, it is important to monitor the use of these supplements with a specialist to ensure the health and safety of both mother and baby.

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