Progesterone is often described as a calming hormone. In many women, it promotes sleep, relaxation, and emotional steadiness.
So why do some women experience intense anxiety, irritability, depression, or emotional volatility when progesterone rises?
The answer lies not in progesterone itself — but in how the brain responds to its metabolite: allopregnanolone (ALLO).
Understanding ALLO helps explain PMDD, perimenopausal mood changes, and why symptoms can occur even when hormone levels are completely normal.
Allopregnanolone (ALLO) is a neurosteroid made when the body metabolizes progesterone.
ALLO acts directly on GABA-A receptors, the brain’s primary inhibitory (calming) system — the same system targeted by medications like benzodiazepines.
In theory:
For many women, this pathway works beautifully.
But for others, it doesn’t.
Landmark research from the NIH has shown that women with PMDD have normal estrogen and progesterone levels.
What’s different is how their brains respond to hormonal change.
In experimental studies, when ovarian hormones were completely suppressed, PMDD symptoms disappeared.
When estrogen and progesterone were added back — at normal physiologic levels — symptoms returned rapidly.
This proves the issue is not too much or too little hormone.
It’s neurobiological sensitivity to fluctuation.
In hormone-sensitive brains, rapid changes in ALLO can destabilize GABA-A receptors instead of calming them.
This can result in:
Rather than soothing the nervous system, ALLO’s rise and fall becomes activating.
This is why PMDD symptoms often:
This same mechanism helps explain perimenopausal mood changes.
During perimenopause:
Some cycles have:
These “loop cycles” cause repeated ALLO rises and crashes — reactivating the same brain circuitry seen in PMDD.
This is why many women say:
“I haven’t felt this way since my worst PMS — but now it lasts all month.”
ALLO is:
A blood test can show:
…and still completely miss what the brain is experiencing.
This is why symptom patterns matter more than lab values when assessing hormonally driven mood changes.
SSRIs are uniquely effective in PMDD — often at:
Why?
Because SSRIs:
They don’t just treat mood — they help stabilize the brain’s response to hormonal change.
Effective treatment focuses on reducing hormonal volatility and supporting neurochemical stability.
This may include:
The goal isn’t to eliminate hormonal changes— it’s to help the brain stop overreacting to them.
If your mood shifts feel sudden, intense, and hormonally timed — your experience is real, biological, and treatable.
Listening to symptoms with curiosity — not dismissal — is often the first step toward real relief.
Conscious Psychiatry is a specialized mental health practice that takes a holistic, evidence-based approach to women's mental wellness throughout all life stages. Founded by Jordan Gough, a Psychiatric Nurse Practitioner with extensive experience in critical care, our practice combines traditional and alternative treatment options to provide comprehensive, personalized care.
Our Philosophy: We believe that every individual deserves to be heard, supported, and empowered on their journey to better mental health. Our approach is rooted in empathy, empowerment, and evidence-based practices, ensuring that you feel validated and understood throughout your treatment.
Specialized Services:
Our Approach: We treat the whole person, not just symptoms. By integrating mental health support, hormone therapy when appropriate, and lifestyle medicine, we help women navigate life's transitions with confidence and optimal well-being.
Insurance and Accessibility: We accept insurance for psychiatric evaluations and follow-ups, making mental health care accessible. Our hormone therapy services are offered on a transparent, self-pay basis to ensure the comprehensive time and attention this specialized care requires.
Located in Denver, Colorado, Conscious Psychiatry serves women throughout the region who are seeking compassionate, expert care during perimenopause, menopause, and beyond. We're here to help you reclaim your mental wellness and thrive through life's changes.
Contact us today to learn how we can support your journey to optimal mental and hormonal health.
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Address: 950 S Cherry St Suite 1675, Denver, CO 80246
