From the Guidelines
Micronized progesterone is generally considered a safer option compared to synthetic progestogens, such as medroxyprogesterone acetate (MPA) and norethisterone acetate (NA), due to its more favorable profile in terms of cardiovascular risk, blood pressure, and thrombotic risk. Micronized progesterone has a molecular structure identical to the body's natural progesterone, which may contribute to its improved safety profile 1. Common synthetic progestogens, including MPA and NA, have been shown to have negative effects on lipid profiles, vasomotion, and carbohydrate metabolism, whereas micronized progesterone has been demonstrated to minimize hormonal-related cardiovascular risks and have a neutral or beneficial effect on blood pressure 1.
Key Points to Consider
- Micronized progesterone is associated with fewer adverse effects on lipid profiles, blood pressure, and glucose metabolism compared to synthetic alternatives 1.
- The European Society for Human Reproduction and Embryology (ESHRE) recommends micronized progesterone as a progestogen in hormone replacement therapy (HRT) in adult women with ovarian insufficiency due to its safer pharmacological profile 1.
- Individual responses to micronized progesterone and synthetic progestogens may vary, and patient preference, cost, and availability should be considered when prescribing HRT 1.
- The dose of micronized progesterone for HRT is typically 100-200 mg daily, often taken at bedtime to minimize side effects like drowsiness.
Synthetic Progestogens
- Medroxyprogesterone acetate (MPA) is a synthetic progestogen that has been shown to have negative effects on cardiovascular risk, lipid profiles, and carbohydrate metabolism 1.
- Norethisterone acetate (NA) is another synthetic progestogen that has been evaluated in women with premature ovarian insufficiency, but its safety profile is not as well-established as micronized progesterone 1.
Clinical Implications
- Clinicians should consider the potential benefits and risks of micronized progesterone and synthetic progestogens when prescribing HRT to women with ovarian insufficiency.
- Patient education and counseling are essential to ensure that women are informed about the available options and can make informed decisions about their HRT regimen 1.
From the Research
Comparison of Micronized Progesterone and Synthetic Progestogens
- Micronized progesterone may be a safer option compared to synthetic progestogens, as it does not increase cell proliferation in breast tissue in postmenopausal women, unlike synthetic medroxyprogesterone acetate (MPA) 2.
- The protective effect of progestogens against hyperplasia and endometrial cancer does not appear to differ with different progestogens, but appears to be affected by the regimen and thus the dose, with continuous combined treatment conferring better protection 2.
- Micronized progesterone is a clinically effective, well-tolerated, and cost-comparable alternative to MPA, with improvements in climacteric symptoms and quality of life 3.
Synthetic Progestogen Options
- Medroxyprogesterone acetate (MPA) is a synthetic progestin that is commonly used in hormone therapy, but it has been shown to have non-specific effects, including glucocorticoid activity, which may contribute to its increased risk of breast cancer 2.
- Norethindrone acetate is another synthetic progestogen that is used in hormone therapy, but its effects on the breast and breast cancer risk are not well understood 4.
Micronized Progesterone Characteristics
- Micronized progesterone is a natural progesterone that is readily absorbed and reaches peak serum concentrations from 1 to 4 hours after administration 3, 5.
- The extent of absorption of micronized progesterone increases with increasing age, and there is considerable intersubject variability in the extent of progesterone absorbed after administration of oral micronized progesterone 5.