Progesterone vs Progestin in HRT: What Is the Difference?
Natural micronised progesterone vs synthetic progestins in HRT explained. Covers breast cancer risk, sleep benefits, mood side effects, NICE guidance, and what to ask.
The Progesterone Question in HRT
If you have a uterus and are taking HRT, you need a progestogen alongside estrogen to protect the uterine lining from overstimulation that could lead to endometrial hyperplasia. The progestogen component is where there is significant variation in what women are prescribed and how those choices affect their experience. The two broad categories are body-identical progesterone (most commonly known by the brand name Utrogestan in the UK) and synthetic progestins (also called progestogens), which include norethisterone, levonorgestrel, medroxyprogesterone acetate, and others. These are not interchangeable, and the differences matter for breast cancer risk, sleep quality, mood, and tolerability.
What Body-Identical Progesterone Is
Micronised progesterone is chemically identical to the progesterone produced by the human body. It is derived from plant sources (wild yam or soy) and processed into a form the body recognises as its own hormone. In the UK, it is available as Utrogestan capsules, which can be taken orally or used vaginally. When taken orally, micronised progesterone is metabolised into neurosteroids, particularly allopregnanolone, which act on GABA receptors in the brain. This is the mechanism behind its sedating and anxiolytic effects, making it particularly beneficial when taken at bedtime. For women who have struggled with poor sleep during perimenopause, this effect is often welcome and significant.
What Synthetic Progestins Are
Synthetic progestins were developed to be taken orally, to be more potent than natural progesterone, and to have a longer duration of action. Norethisterone and levonorgestrel have androgenic activity: they mimic testosterone to varying degrees, which can cause acne, bloating, low mood, and reduced libido in some women. Medroxyprogesterone acetate (MPA), used in the combined oral contraceptive pill and some older HRT formulations, has been associated with the higher breast cancer risk seen in older HRT studies. The key 2002 Women's Health Initiative study, which triggered widespread HRT discontinuation, used MPA rather than body-identical progesterone, and this distinction is now central to contemporary understanding of HRT safety.
Breast Cancer Risk: What the Evidence Shows
Current evidence, including the large UK Million Women Study and data reviewed by NICE, indicates that the type of progestogen used in HRT influences breast cancer risk. Combined HRT containing synthetic progestins is associated with a higher risk than estrogen-only HRT or HRT containing micronised progesterone. The absolute risk increase remains small in the context of everyday risk factors: less than that associated with drinking one to two glasses of wine per day or being overweight. However, for women who want to minimise any additional risk, the shift toward body-identical progesterone is supported by the available evidence. It is important to note that estrogen-only HRT, used by women who have had a hysterectomy, does not carry the same progestogen-related risk.
Mood Side Effects
Mood disruption from the progestogen phase of HRT is a common reason women struggle to stay on treatment. Norethisterone and other androgenic progestins can cause pre-menstrual-style symptoms including irritability, low mood, and anxiety during the days they are taken. Some women find this predictable enough to manage; others find it unacceptable. Micronised progesterone is generally better tolerated from a mood perspective, partly because of its GABAergic calming effect. For women who have had significant PMS or PMDD historically, this difference is especially clinically relevant, and it is worth raising with your prescriber if you are currently on a synthetic progestin and experiencing mood changes.
NICE Guidance and What Prescribers Are Moving Toward
The 2015 and updated NICE guidelines on menopause acknowledge the differences between progestogens and support informed choice. Prescribers increasingly offer body-identical progesterone as a first-line option, though availability and prescribing patterns vary between practices. Some GPs are still more familiar with older synthetic formulations, particularly those integrated into combined patches. If you are not in the UK, availability will depend on local regulatory approvals. Utrogestan is licensed in the UK as an HRT component. If you are curious about switching from a synthetic progestin to micronised progesterone, it is a valid question to raise at your next review and one your GP should be able to address or refer you for.
Asking Your Prescriber the Right Questions
When discussing your HRT regimen, it helps to ask specifically: which progestogen am I taking, and what type is it? If the answer is norethisterone, levonorgestrel, or medroxyprogesterone acetate, you can ask whether body-identical micronised progesterone is an option for you. Mention any mood changes, bloating, or sleep issues you experience during the progestogen phase, as these are clinical signals that the type or dose may need adjustment. If your GP is unfamiliar with these distinctions, a referral to a menopause specialist or clinic is reasonable. Getting this component of your HRT right can make a significant difference to how well you tolerate treatment overall and how consistently you are able to stay on it.
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