All About Progesterone
Progesterone: A balancing act
Often referred to as the calming or balancing hormone, progesterone acts to maintain hormonal equilibrium within our bodies.
As a menopause specialist, I often see patients who feel overwhelmed by the range of hormone therapy (HT) options available. With the amount of noise out there, I get it—it’s confusing, so let’s break it all down.
Progesterone plays a vital role in managing menopausal symptoms, especially for women using estrogen. It’s crucial for preventing estrogen-induced complications, such as endometrial hyperplasia (an abnormal growth of the tissue that lines our uterus), and improving overall quality of life.
Role of Progesterone in the Body
Progesterone is a hormone primarily produced by the ovaries after ovulation during the luteal phase of the menstrual cycle. It plays a critical role in regulating the menstrual cycle, supporting pregnancy, and maintaining the uterine lining. Beyond reproductive health, progesterone has widespread effects on the brain, bones, and cardiovascular system.
Uterine Health: Progesterone prepares the endometrium (the lining of the uterus) for potential implantation of a fertilized egg and prevents overgrowth caused by estrogen.
Brain Function: Progesterone is converted into allopregnanolone, a neurosteroid that has calming effects, helps regulate mood, and promotes better sleep.
Bone and Cardiovascular Health: Progesterone contributes to bone density and supports vascular function.
Changes During Perimenopause and Menopause
During perimenopause, ovulation becomes irregular, leading to fluctuations and eventual declines in progesterone levels. By menopause, ovarian production of progesterone ceases entirely.
The drop in progesterone contributes to symptoms such as irregular periods (heavier, lighter, less often, more often), mood changes, anxiety, interrupted sleep, hot flashes, and night sweats.
Why Progesterone Therapy Helps
Adding progesterone as part of HT can:
Alleviate Symptoms: Progesterone’s calming effects via allopregnanolone can reduce anxiety, promote restful sleep, and stabilize mood.
Stabilize and Protect the Endometrium: Progesterone counteracts estrogen’s stimulatory effects on the uterine lining, preventing abnormal tissue growth and subsequent irregular or abnormal bleeding patterns.
Enhance Neuroprotection: Allopregnanolone’s influence on the brain supports cognitive function and may lower the risk of neurodegenerative conditions.
Choosing a progesterone
When it comes to selecting the right type of progesterone for hormone therapy, you have quite a few options. Progesterone is not one-size-fits-all; its effects on the body depend on the form, dosage, and delivery method. From oral micronized progesterone to vaginal applications, progestin-releasing IUDs, and even innovative nasal options, each choice offers distinct advantages.
Here are a couple of KEY POINTS to consider:
Only synthetic progestins like those found in oral contraceptives or long-acting contraceptives (i.e., IUDs) offer contraceptive benefits, and during perimenopause, this is especially important as you can still conceive a pregnancy up until you have gone ONE FULL YEAR without a menstrual cycle.
Bioidentical micronized progesterone is best for sleep and anxiety relief as it converts to a secondary hormone known to stimulate the calming pathways in our central nervous system.
All women, even those who do not have their uterus anymore, can benefit from micronized progesterone, although it is important to note that approximately one in ten women will have a sensitivity to natural progesterone.
Micronized Progesterone vs. Synthetic Progestins
Micronized/Bioidentical Progesterone: Derived from plant sources, micronized progesterone is chemically identical to the hormone produced by the body. It is well-tolerated, effective for perimenopausal and menopausal symptom relief, and supports endometrial protection.
Synthetic Progestins: These laboratory-made compounds mimic progesterone’s effects but are not identical in structure. They often have stronger side effects, including mood disturbances, bloating, and an increased risk of certain health conditions, such as blood clots. But unlike micronized progesterone, offer contraceptive benefits and cycle regulation.
Oral Progesterone: The Gold Standard
Micronized oral progesterone is widely regarded as the safest and most effective option for endometrial protection:
Standard Dosing: A regimen of 200 mg/day for 12–14 days per month prevents endometrial hyperplasia effectively, even with long-term use. However, progesterone can be dosed anywhere from 100 mg/day to 400 mg/day depending on individual patient needs, preferences and degree of symptom relief with a particular dose.
Continuous vs. Cyclical Use: Patients on continuous combined HT (100 mg/day) benefit from consistent symptom relief and protection.
High-Dose Estrogen Adjustment: Women on higher doses of estrogen (≥0.075 mg transdermal patch or 1.5 mg oral) may require 200 mg/day continuously or 300 mg/day for 12–14 days per month to maintain adequate endometrial protection.
Systemic Benefits: In addition to endometrial protection, oral progesterone supports better sleep quality, improves temperature dysregulation (hot flashes/night sweats), decreases anxiety, and improves mood changes but may cause drowsiness, gastric reflux or bloating in some users.
Progesterone Intolerance: Some individuals may be particularly sensitive to progesterone, and 1% of women have a true intolerance to the medication, often resulting in a rash when administered. These individuals require a different progestogen formulation for their hormone therapy regimen.
Alternatives to Oral Micronized Progesterone (OMP)
Vaginal Progesterone: Targeted Relief
For localized action with minimal systemic side effects, vaginal progesterone is an excellent choice:
Regimen Options: Studies support the use of 100 mg daily or 4% gel (45 mg/day) for 10 days per month.
Patient-Friendly Profile: Vaginal administration bypasses first-pass liver metabolism, reducing risks of side effects like mood changes or fatigue/drowsiness and gastroesophageal reflux exacerbation.
MAKE SURE TO DISCUSS THIS WITH A HEALTHCARE PROFESSIONAL PRIOR TO CONVERTING OMP TO VAGINAL ROUTE TO ENSURE PROPER DOSING
Progestin-Releasing IUDs
For women seeking a non-oral option for endometrial protection during HRT, a progestin-releasing intrauterine device (IUD) is an effective choice. The IUD provides:
Localized Protection: It delivers progestin directly to the uterine lining, providing exceptional uterine lining protection against the stimulatory effects of estrogen and cycle regulation and contraception.
Ease of Use: Once inserted, the IUD can remain effective for up to 8 years, offering a long-term solution for endometrial protection.
Synthetic Oral Progestins
Synthetic progestins, often used in menopausal hormone therapy (MHT) and oral contraceptive pills are laboratory-made compounds designed to mimic some effects of natural progesterone.
Unlike bioidentical progesterone, synthetic progestins are chemically altered, allowing them to have a longer half-life and increased potency. These modifications can make them effective at preventing endometrial hyperplasia. They offer superior cycle regulation to OMP and contraceptive benefits and, frankly, just work better than OMP for some women.
Forms such as norethindrone acetate, drospirenone, and levonorgestrel are all excellent options for individuals who require an alternative to OMP.
Transdermal Progesterone: A Mixed Bag
Transdermal progesterone creams are often marketed as a natural solution, but they come with limitations:
Endometrial Protection with Estrogen: Research demonstrates that transdermal progesterone (e.g., 16–64 mg/day) does not consistently induce the secretory changes required to protect the endometrium when combined with estrogen. This limits its use for women on combined HRT.
Standalone Benefits: Transdermal progesterone can alleviate mild menopausal symptoms such as mood changes and sleep disturbances when used alone. However, it should not be relied upon for endometrial protection in the absence of a hysterectomy.
Dosing Challenges: Serum and saliva levels of transdermal progesterone vary widely, complicating dose titration and making reliable monitoring difficult.
Nasal Progesterone: An Emerging Option
Nasal progesterone is a promising alternative and something to pay attention to for the future:
Efficacy: Preliminary studies show that 34 mg/day induces secretory changes in the endometrium, suggesting reliable endometrial protection.
Advantages: This method avoids first-pass metabolism, offers rapid absorption, and mimics natural hormone fluctuations. However, further research is necessary to establish long-term safety and refine dosing guidelines.
Making an Informed Decision
When considering progesterone options, it’s essential to tailor the therapy to your individual needs. Here are some practical recommendations:
For Combined HT:
Use oral micronized progesterone (at least 100–200 mg/day).
Adjust dosing for higher estrogen regimens as needed.
Consider a progestin-releasing IUD for localized endometrial protection alone or in addition to OMP use.
For Localized Therapy:
Vaginal progesterone (100-400 mg daily) is ideal for women seeking minimal systemic exposure. Monitoring the thickness of the uterine lining may be required to ensure adequate protection.
For Natural Alternatives:
Transdermal progesterone may be suitable for mild symptom relief in women not using estrogen but is typically not recommended beyond this application.
References
Wren BG, et al. Sequential transdermal progesterone cream: Endometrial and hormone outcomes. Climacteric, 2000.
Du JY, et al. Progesterone delivery via cream or gel: Cross-over study findings. Menopause, 2013.
Leonetti HB, et al. Topical progesterone cream and vasomotor symptom relief. Fertility and Sterility, 2003.
Stute P, et al. Micronized progesterone for menopause: A systematic review. Climacteric, 2016.
Hemoda H, Panay N, Pedder H, et al. The British Menopause Society & Women’s Health Concern 2020 recommendations on HRT. Post Reproductive Health, 2020.
Pelissier C, et al. Clinical outcomes of vaginal progesterone use. European Journal of Obstetrics & Gynecology, 2002.
Cicinelli E, et al. Nasal progesterone: Hormone levels and endometrial effects. Fertility and Sterility, 1993.
Prior JC. Progesterone for hot flushes: Evidence-based guidelines. Journal of Obstetrics and Gynaecology Canada, 2018.
Pinkerton JV, et al. Micronized progesterone: Clinical applications in menopause management. Menopause, 2021.
