One of the areas I have found most challenging in menopause care is choosing the right progestogen. Not because options are lacking — but because there are several, each with subtly different properties, and the differences are often poorly explained in everyday practice.
I realised I was not as clear as I wanted to be on how the commonly used progestogens really differ from one another. So I went back to the evidence. This post is a summary of what I found when I looked more closely at three widely used options in hormone replacement therapy (HRT): micronised progesterone (often prescribed as Utrogestan although other versions are available), dydrogesterone, and drospirenone.
Why the Progestogen Matters
In women with a uterus, progestogens are essential in HRT to protect the endometrium from unopposed oestrogen stimulation. But endometrial protection is only part of the story.
Different progestogens have different effects on:
– mood and sleep
– bleeding patterns
– metabolism and fluid balance
– breast tissue
– cardiovascular and thrombotic risk
Understanding these differences matters — particularly in the perimenopause, where women may be more sensitive to hormonal effects and more likely to stop treatment if side effects are problematic.
Micronised Progesterone: Closest to Physiology
Micronised progesterone is chemically identical to endogenous progesterone. The “micronised” part simply refers to the mechanical process used to improve absorption by reducing the particle size.
What stands out when reviewing the literature is its receptor selectivity. Micronised progesterone acts primarily at progesterone receptors, with minimal off-target effects. This likely explains its relatively favourable profile in relation to mood, lipids and cardiovascular risk.
Orally, it undergoes significant first-pass metabolism, which reduces bioavailability but also produces metabolites such as allopregnanolone. Clinically, this often translates into a sedative effect, which some women find helpful for sleep — particularly when taken at night — while others find it limiting.
When used in evidence-based doses, micronised progesterone provides reliable endometrial protection, although bleeding patterns can be variable and sometimes require adjustment.
Dydrogesterone: Targeted and Well Tolerated
Dydrogesterone is a synthetic progestogen, but one with a structure that closely resembles natural progesterone. It has high oral bioavailability and strong receptor selectivity, meaning effective endometrial protection can be achieved at relatively low doses.
One of the consistent findings across studies is its predictable bleeding profile when used sequentially. Withdrawal bleeds tend to be more regular, with fewer episodes of unscheduled bleeding compared to some other synthetic progestogens.
Importantly, dydrogesterone appears metabolically neutral. It is non-androgenic, does not adversely affect lipid or glucose metabolism, and is generally well tolerated in terms of mood and breast tenderness. Although often used off-label for HRT in the UK, its safety and efficacy data are reassuring.
Drospirenone: Different by Design
Drospirenone is structurally quite different from the other two. It is derived from spironolactone and has anti-mineralocorticoid and anti-androgenic properties.
This gives it a distinct clinical niche. Its ability to counteract sodium and water retention can be particularly helpful for women troubled by bloating, fluid retention or raised blood pressure. Some women also benefit from its anti-androgenic effects on acne or hirsutism.
Drospirenone has demonstrated effective endometrial protection in fixed-dose HRT preparations and is also licensed as a progestogen-only contraceptive (for example, the 4 mg 24/4 regimen). This makes it a useful option in the perimenopause, where contraception may still be required.
However, long-term breast safety data are more limited, and caution is advised in women at risk of hyperkalaemia, particularly those taking other potassium-sparing medications.
Breast and Cardiovascular Safety: What the Evidence Suggests
Breast cancer risk remains one of the most common concerns around HRT. Observational data — particularly from large cohort studies — suggest that micronised progesterone and dydrogesterone are associated with a lower breast cancer risk compared with some older synthetic progestogens.
These data are not from randomised trials and must be interpreted cautiously, but they are broadly reassuring. Thrombotic risk appears to be driven far more by the route of oestrogen administration than by progestogen choice, with transdermal oestrogen consistently favoured.
Evidence around drospirenone and thrombotic risk in HRT is still evolving, but current data do not suggest a clear excess risk.
Practicalities Matter Too
Beyond pharmacology, practical considerations influence real-world prescribing. Cost, licensing, availability, and flexibility of dosing all matter — as does the woman’s own experience of side effects.
It is also important to remember that oral progestogens are not the only option. The levonorgestrel-releasing intrauterine system provides highly effective endometrial protection with minimal systemic exposure and remains an excellent choice for many women, particularly those who want long-acting contraception alongside HRT.
What This Changed for Me
Looking back at the evidence helped me move away from thinking about progestogens as interchangeable. They are not. Each has strengths, limitations and a particular place in practice.
For women with higher concern about breast or cardiovascular risk, micronised progesterone or dydrogesterone are often preferable. For those struggling with fluid retention, acne, or needing contraception, drospirenone may offer advantages. And for many, the “best” choice is the one that balances evidence with lived experience.
Shared decision-making, grounded in up-to-date evidence and individual priorities, is key.
Further Reading
British Menopause Society. Progestogens and Endometrial Protection: Tools for Clinicians
NICE Guideline NG23: Menopause: diagnosis and management
Stevenson JC et al. Progestogens in menopausal hormone therapy. Drugs in Context
Mueck AO et al. Dydrogesterone in HRT. Maturitas
Palacios S et al. Drospirenone in hormone therapy. Maturitas
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