Body-Identical vs Synthetic Progesterone: What Women Need to Know
Body-identical and synthetic progestogens work differently and have different side effect profiles. Learn which option may suit your HRT regimen better.
Why Progestogen Type Matters in HRT
When women with a uterus take HRT, a progestogen is always included alongside estrogen to protect the uterine lining from thickening. For many years the progestogen component received less attention than estrogen, but growing evidence suggests that the type of progestogen used makes a significant difference to both the side effect experience and the long-term risk profile of HRT. The main choice is between body-identical progesterone, specifically micronised progesterone, and synthetic progestogens such as norethisterone, levonorgestrel, and medroxyprogesterone acetate. Understanding the differences helps women have a more informed conversation with their prescriber.
What Body-Identical Progesterone Is
Body-identical progesterone, also called micronised progesterone, is a hormone that is chemically identical to the progesterone produced by the human ovaries. It is derived from plant sources (typically wild yam or soy) and then processed to create a molecule that matches human progesterone exactly. In the UK it is most commonly available as Utrogestan capsules. Because the molecule matches the body's own progesterone, it interacts with progesterone receptors in the same way as the hormone your body would naturally produce. This is distinct from synthetic progestogens, which are structurally different and may interact with other hormone receptors beyond the progesterone receptor.
What Synthetic Progestogens Are
Synthetic progestogens, also called progestins, are compounds developed to mimic the uterine-protective effects of progesterone but are structurally different from the natural hormone. Different synthetic progestogens have different receptor binding profiles: some have androgenic (testosterone-like) activity, some have glucocorticoid activity, and some have anti-mineralocorticoid properties. These additional receptor interactions are the main reason synthetic progestogens tend to produce a broader range of side effects than micronised progesterone. Norethisterone, for example, has androgenic activity that can contribute to acne, water retention, and mood changes. Medroxyprogesterone acetate, common in older combined HRT formulations, is associated with a higher risk profile in some breast cancer studies.
Side Effect Differences in Practice
Women who switch from synthetic progestogens to micronised progesterone frequently report improvements in mood stability, sleep quality, and general wellbeing. Micronised progesterone has been found to have some mild sedative and anxiolytic (anxiety-reducing) properties through its conversion to allopregnanolone, a neurosteroid that acts on GABA receptors in the brain. This is why some prescribers recommend taking Utrogestan at night. Synthetic progestogens do not share this profile and can in some cases worsen mood, anxiety, and sleep. For women who have struggled with PMS or PMDD in the past, the progestogen phase of sequential HRT using synthetic progestogens can trigger similar symptoms, whereas micronised progesterone tends to be better tolerated.
Breast Cancer Risk: What the Research Shows
One of the most clinically significant differences between body-identical and synthetic progestogens relates to breast cancer risk. Large observational studies, including data from the E3N cohort study in France, suggest that combined HRT using micronised progesterone is associated with a lower breast cancer risk than combined HRT using synthetic progestogens. The WHI study, which generated significant concern about HRT and breast cancer in the early 2000s, used medroxyprogesterone acetate, a synthetic progestogen, and its findings are not considered directly applicable to regimens using micronised progesterone. This evidence is not definitive and is still being assessed, but many specialist menopause clinicians regard micronised progesterone as the preferred progestogen choice for this reason.
Availability and Practical Considerations
Micronised progesterone is widely available in the UK on NHS prescription, though not all GPs are familiar with prescribing it and some may default to synthetic alternatives. Menopause specialists are generally more likely to offer micronised progesterone as a first-line option. Utrogestan capsules can be taken orally or used vaginally as pessaries for women who experience systemic side effects (such as drowsiness) when taking them orally. The vaginal route reduces systemic absorption and concentrates the progestogen effect on the uterus, which suits some women well. Synthetic progestogens are also available in various forms including combined patches, tablets, and the Mirena IUS (intrauterine system), which delivers levonorgestrel locally to the uterus with minimal systemic absorption and is a practical option for some women.
Choosing the Right Option for You
If you are starting HRT or considering a change to your current regimen, asking your prescriber about micronised progesterone is a reasonable starting point if you have found synthetic progestogens difficult to tolerate, if you have a history of PMS or PMDD, or if you are concerned about minimising breast cancer risk. Keep in mind that individual responses vary and some women do well on synthetic progestogens without significant side effects. The Mirena IUS is worth considering if you prefer not to take oral progesterone or use patches, as it provides effective endometrial protection with very low systemic progesterone levels. Tracking your symptoms carefully across the progestogen phase of your cycle, and noting whether they worsen on synthetic progestogens, gives you concrete evidence to bring to a prescription review. PeriPlan lets you log symptoms and track patterns over time to support exactly these kinds of conversations.
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