Progesterone Sensitivity: When Your Hormones Own the Mood
What is "Progesterone Sensitivity"?
If you’re one of those women who can feel every hormonal shift, you’re not imagining it.
Progesterone sensitivity—sometimes called progesterone intolerance—is when your body reacts strongly (and not always positively) to progesterone. This can happen with your own naturally produced progesterone (endogenous) or from prescribed hormones (exogenous), like those in HRT or contraceptives.
For many women, progesterone is calming, promoting sleep and emotional balance. But for a sensitive subgroup, it can trigger mood swings, anxiety, insomnia, skin changes, or even allergic-type reactions.
Why It Matters: Mood, Skin, and More
Mood & Mental Health
Research published in Best Practice & Research: Clinical Obstetrics & Gynaecology (2020) highlights that while, generally, exogenous progesterone isn’t linked to negative mood in the broader population, a vulnerable subgroup may experience pronounced effects—particularly if they already struggle with psychiatric conditions. Progesterone’s neuroactive metabolite, allopregnanolone, acts on the GABA_A receptor and typically induces relaxation—but in sensitive individuals, altered receptor responses may instead lead to anxiety, irritability, or cognitive disruption.
Dermatological Reactions
A rare but striking manifestation is progesterone hypersensitivity—cyclical skin eruptions like urticaria, eczema, or even anaphylaxis, occurring in the luteal phase (days 3–10 before menstruation) that resolve after menses. A documented case involved a woman whose skin lesions subsided during pregnancy and postpartum, after a positive intradermal test confirmed sensitivity.
Brain–Hormone Interactions & Underlying Mechanisms
Neuroactive steroid action: Allopregnanolone and other metabolites modulate GABA_A receptors. Instead of calming, hypersensitive individuals may experience mood destabilisation or cognitive disruption.
Genetic and neurochemical vulnerability: Some women—especially those with PMDD—process progesterone differently at a cellular level. Studies report altered GABA-A receptor sensitivity to allopregnanolone and evidence of genetic modulation, contributing to exaggerated mood responses
Do Some Progestins Play Nicer Than Others?
Not all progestins are equal. Here’s a breakdown of how different types compare in women with progesterone sensitivity.Not necessarily. Many women do well once the right type/dose/route is found.
Body-identical progesterone
Micronized progesterone — the “natural” version used in many HRT prescriptions — converts into allopregnanolone, a brain chemical that usually calms things down. But in women with progesterone sensitivity, this metabolite can misfire and cause anxiety or mood dips instead.
Tips that sometimes help: using it vaginally rather than orally (to avoid big peaks) or taking it continuously instead of in cycles.
Dydrogesterone
This one is a close chemical relative of natural progesterone, but with a very clean profile — no androgenic or “testosterone-like” effects. Studies suggest it’s well-tolerated, even when combined with estrogen in HRT. For women who’ve struggled with mood changes on other progestins, dydrogesterone is often a softer landing. This progestin isn’t available as a contraceptive but it is combined with oral estradiol for HRT with the brand name Femoston and is newly available privately as a standalone progesterone for HRT.
Drospirenone
Drospirenone (often paired with a low dose of estrogen in a 24/4 pill) doesn’t just avoid mood problems — it actually has evidence for improving PMDD symptoms. It’s anti-androgenic and anti-bloating, and several trials back up its benefits for women whose worst week of the month feels unbearable. Drosperinone can be found alone as a progesterone only pill with the brand name Slynd, which is a great option for women who can’t take the combined oral contraceptive pill, or combined with ethinylestradiol in low dose as Eloine or normal dose as Lucette/Yacella/Yasmin.
Nomegestrol acetate
This one is paired with “real” estradiol (instead of synthetic ethinyl estradiol) in certain pills. Early studies — and some real-world experiences — suggest good mood stability and tolerability. It doesn’t have the decades of data that others do, but it’s showing promise for sensitive women. Read more about nomegestrol in my blog about Zoely and PMDD.
Levonorgestrel
Levonorgestrel is one of the most widely used progestins. In pill or implant form, it has androgenic activity, which some women find harsh. The coil (IUD) version delivers low systemic levels, but large studies have found a dose-related link between levonorgestrel IUDs and new-onset depression. Not every woman is affected, but if you already have mood sensitivity, it’s something to weigh up carefully. The IUD is available in different strengths, with the Mirena being the standard strength and lasting for 8 years as a contraceptive or 5 years for endometrial protection with HRT. For women who can’t tolerate the dose in the Mirena coil, low dose Kyleena, or super low dose Jaydess, are also available for women who need contraception (sadly at the moment due to a lack of data these lower dose coils can’t be used as endometrial protection with HRT).
Dienogest
Dienogest is widely prescribed for endometriosis because it works well for pain. Most women do fine on it, but a small percentage report depressed mood — occasionally severely. If you’re progesterone-sensitive, it’s not an automatic “no,” but it does mean your mood needs monitoring in the first few months. You can read more information about dienogest in my blog about new treatments for endometriosis.
The older ones: norethisterone, medroxyprogesterone, etc.
Older progestins like norethisterone (NET) and medroxyprogesterone acetate (MPA, found in Depo-Provera) have been around for ages. They tend to have more androgenic or glucocorticoid “side activities,” and for sensitive women, that can sometimes translate to less predictable mood effects. Some do fine — others don’t.
So… which progestin is best if you’re sensitive?
Here’s a simple way to think about it:
Need contraception + PMDD help? A drospirenone pill (24/4 schedule) is the most evidence-backed.
Need HRT endometrial protection? Dydrogesterone is often the most gentle; vaginal micronized progesterone can work with careful scheduling.
Need endometriosis treatment? Dienogest is effective — just keep an eye on mood.
Thinking IUD? Levonorgestrel is convenient, but go in with eyes open about possible mood links.
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Not directly—diagnosis is based on symptoms, timing, and trial of alternatives.
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Not necessarily. Many women do well once the right type/dose/route is found.
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Yes. Stress management, sleep hygiene, and limiting alcohol/caffeine can all reduce symptom intensity.
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They overlap. PMDD is cycle-related mood sensitivity to normal hormonal changes, while progesterone sensitivity also includes reactions to prescribed hormones.