A colleague recently asked me:   "Can I use double-dose Cerazette ® for endometrial protection in someone with progesterone intolerance?"

The short answer is:

Yes

But I don't think that's the most important question.

The better question is:

"Is it the best option for this particular woman?"

RECAP: What do we actually mean by " progesterone intolerance"?

"Progesterone intolerance" is a label that covers many different symptoms.  Some women experience sedation, brain fog or fatigue. Others develop anxiety, low mood or irritability. Some notice bloating, breast tenderness or worsening PMDD.

These symptoms don't necessarily have the same cause, so they won't always have the same solution.

Before changing treatment, I think it's worth asking:

What has she actually tried?

• Is it one progestogen, or several?
• Is it progesterone itself, or the cyclical starting and stopping?
• Is she perimenopausal with significant hormonal fluctuation?
• Is her oestrogen adequately replaced?
• Would ovulation suppression actually improve her symptoms?
• So where does Cerazette® fit?

Cerazette® (desogestrel)  suppresses ovulation in most women, creating much greater hormonal stability.

For some women, the problem isn't progesterone itself - it's the continual rise and fall of hormones during perimenopause.

For others, oral micronised progesterone causes unacceptable sedation, whereas desogestrel is much better tolerated.

Importantly, the 2026 British Menopause Society (BMS) and Australasian Menopause Society (AMS) guidance now recognise double-dose desogestrel (Cerazette, 150 micrograms once daily) as an off-label option for endometrial protection alongside systemic oestrogen. Slinda ® (4mg drospirenone) is also recognised as an off-label alternative in appropriately selected women.

But is doubling Cerazette® always the answer?  Not necessarily.  Sometimes the woman simply needs more oestrogen.  Sometimes suppressing ovulation improves symptoms enough that she can later tolerate micronised progesterone.  Sometimes another progestogen is a better fit because of its pharmacology.  And sometimes she genuinely cannot tolerate multiple progestogens and needs a different strategy altogether.

Progestogens are not just endometrial protectors

One of the biggest shifts in my own practice has been recognising that progestogens do much more than protect the endometrium.

Some suppress ovulation.

Some are anti-androgenic.

Some are more sedating.

Some have anti-mineralocorticoid properties.

Choosing the right progestogen isn't just about asking "Which is safest?"

It's also about asking:

" Which progestogen is most likely to help this woman, at this stage of her life?"

Some decisions are about short-term symptom control and hormonal stability. Others require us to think about longer-term exposure and cumulative risks such as meningioma, cardiovascular disease and breast cancer.

For many women, receiving effective menopausal hormone therapy with a synthetic progestogen is likely to be far more beneficial than receiving no hormone therapy at all because no acceptable alternative was considered.

Evidence and limitations

Both desogestrel and drospirenone remain off-label options for endometrial protection alongside systemic oestrogen.

Although these options are now included within BMS and AMS guidance, there are currently no large randomised controlled trials directly comparing double-dose desogestrel or drospirenone with micronised progesterone or the levonorgestrel intrauterine system for endometrial safety.

The recommendations are based on available clinical studies, pharmacological understanding, observational evidence, clinical experience and expert consensus. As with all off-label prescribing, informed consent, documentation and appropriate follow-up remain essential.