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Progesterone vs Progestins: What's the Difference and Why It Matters

Progesterone is an essential hormone that plays a critical role in a woman's reproductive health. It is commonly used in hormone replacement therapy (HRT) to help alleviate symptoms of menopause, including hot flashes, mood changes, and sleep disturbances. However, not all forms of progesterone are created equal. In this blog post, we'll discuss the differences between oral micronized progesterone and synthetic progestins and their respective benefits and risks.


What is progesterone anyway?

Progesterone is a hormone that plays a critical role in women's health and I like to think of it as a 'feel good' hormone. In perimenopausal years it's mainly produced by the ovaries, but the adrenal glands and placenta also produce some progesterone. During the menstrual cycle, progesterone levels rise after ovulation, which is when an egg is released from the ovary. This increase in progesterone helps prepare the uterus for pregnancy by thickening the lining and making it more receptive to a fertilized egg. If pregnancy doesn't occur, progesterone levels drop, leading to the shedding of the uterine lining during menstruation.


Progesterone is also essential for a healthy pregnancy. It helps to maintain the lining of the uterus, preventing contractions that could cause a miscarriage. Progesterone also promotes the growth of blood vessels in the uterus, providing nutrients and oxygen to the developing fetus.


Progesterone can also impact mood and emotional well-being. Allopregnenolone, a metabolite of progesterone, has calming effect and may help to reduce anxiety and irritability due to its interaction with GABA receptors in the brain. Some studies have also shown that progesterone may play a role in maintaining healthy bones by stimulating the activity of cells that build and maintain bone tissue.


Progesterone is commonly used in hormone replacement therapy (HRT) to help alleviate symptoms of menopause, including hot flashes, mood changes, and sleep disturbances. Unfortunately, there is a massive misunderstanding regarding the differences between natural progesterone and synthetic progestins.


The Difference Between Oral Micronized Progesterone and Synthetic Progestins

Oral micronized progesterone is a natural, bioidentical hormone that is identical in structure to the progesterone produced by the ovaries. It is made from plant sources and is processed to mimic the body's natural progesterone. Synthetic progestins, on the other hand, are chemically modified versions of progesterone that are not identical to the body's natural hormone. They are often used in birth control pills, hormonal IUDs and some forms of HRT. It is important to know the difference here because these two compounds have drastically different risk and benefit profiles.


Risks of Synthetic Progestins

While synthetic progestins can be effective in controlling the menstrual cycle and alleviating symptoms of menopause, they come with some risks. Several studies have shown

that synthetic progestins can increase the risk of breast cancer in women. One study published in the New England Journal of Medicine found that the use of synthetic

progestins increased the risk of breast cancer by up to 69%. This is a significant concern for women who are considering HRT and want to minimize their risk of breast cancer.


One study followed 1.8 million women for an average of 10.9 years, during which 11,517 cases of breast cancer occurred. Compared to women who had never used hormonal contraception, all current and recent users of hormonal contraception had a relative risk of breast cancer at 1.20. The risk increased from 1.09 with less than 1 year of use to 1.38 with more than 10 years of use. Even after discontinuation of hormonal contraception, the risk of breast cancer remained higher for women who used it for 5 or more years. The absolute increase in breast cancers among current and recent hormonal contraceptive users was approximately 13 per 100,000 person-years, or about 1 extra breast cancer for every 7690 women using hormonal contraception for 1 year.


Something to note is that there is a small amount of progestin contained in hormonal IUDs. Because the amount is so low and very localized to the uterus, there is less risk associated with this form of birth control. I tend to favor this method with patients due to the safety profile and efficacy.


Benefits of Oral Micronized Progesterone

Oral micronized progesterone (OMP) offers several benefits over synthetic progestins, particularly with regard to breast protection when using estradiol hormone replacement therapy. Several studies have shown that oral micronized progesterone may reduce the risk of breast cancer in women who are using HRT. Oral micronized progesterone also provides excellent endometrial protection for women who have a uterus.


In addition to breast protection, oral micronized progesterone has also been shown to improve mood and sleep in women. A study published in the Journal of Women's Health found that women who took oral micronized progesterone reported significant improvements in sleep quality, mood, and anxiety compared to those who took a placebo.


According to a meta-analysis of 3 studies that included 86,881 postmenopausal women, the use of natural progesterone was linked to a significantly reduced risk of breast cancer in comparison to synthetic progestins. Meanwhile, in premenopausal women, anovulation and low levels of serum progesterone were linked to an increased risk of breast cancer. On the other hand, using progesterone has been associated with a lower incidence of uterine and colon cancers, and it may also be helpful in treating other types of cancer, including ovarian, melanoma, mesothelioma, and prostate cancer. In addition, progesterone may have benefits in preventing cardiovascular disease and treating neurodegenerative conditions such as stroke and traumatic brain injury.




Okay, now what?

So, what do we do with this information? The evidence is clear that natural progesterone or OMP provides many benefits without the risks associated with progestins. Unfortunately, in scientific literature and everyday conversations these two very different compounds are conflated, leading to confusion and landing progesterone with a bad rap. Now that you know the facts you can make an informed decision about which you may or may not want to use and spread the word to women you love!


In health,

Dr. J



References:

Lieberman A, Curtis L. In Defense of Progesterone: A Review of the Literature. Altern Ther Health Med. 2017;23(6):24-32.

Mørch LS, Skovlund CW, Hannaford PC, Iversen L, Fielding S, Lidegaard Ø. Contemporary Hormonal Contraception and the Risk of Breast Cancer. N Engl J Med. 2017;377(23):2228-2239. doi:10.1056/NEJMoa1700732

Olsson HL, Ingvar C, Bladström A. Hormone replacement therapy containing progestins and given continuously increases breast carcinoma risk in Sweden. Cancer. 2003;97(6):1387-1392. doi:10.1002/cncr.11205

White E, Malone KE, Weiss NS, Daling JR. Breast cancer among young U.S. women in relation to oral contraceptive use. J Natl Cancer Inst. 1994;86(7):505-514. doi:10.1093/jnci/86.7.505


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