When I turned 35 last year, something shifted.
I started waking up at 2 or 3 AM for no reason, my energy dipped, my skin looked tired.
Nothing in my regimen had changed: I was working out consistently and eating reasonably well.
Because I often work with women in perimenopause and menopause, I started suspecting that the former was knocking at my door. It felt early, but age 35 is when it can begin.
I asked my doctor for a full hormone panel and the results were “within normal range.”
Women unfortunately hear this all the time, along with a slew of other dismissals like “It’s a natural part of aging” or “Let’s get you on Xanax or an SSRI so these symptoms bother you less.”
Medical gaslighting is real, and it’s the reason why I always tell my clients to find a practitioner who is certified by the Menopause Society, and to get more than one opinion.
These changes we feel in our disposition significantly affect our quality of life, and have everything to do with desire and libido.
They also impact our partners who are left scratching their heads, trying to understand what’s going on and how to best support us during this unstable period.
That’s why I invited Jackie Giannelli to the podcast. Jackie is a board-certified family nurse practitioner specializing in women’s health, longevity, and sexual medicine. She has a private practice serving women in New York and Connecticut, and is also a clinical strategist for the new Carolyn Rowan Center at Mount Sinai. She is one of the most rigorous, nuanced, and genuinely funny people I’ve talked to on this subject.
This episode is essentially a masterclass in what’s actually happening inside your body in your late 30s, 40s, and beyond — and what you can do about it. We cover everything from hormone replacement therapy to GLP-1 to peptides.
You can tune in on Youtube, Spotify and anywhere you listen to podcasts.
Here are the highlights:
“Normal” and “optimal” lab results are not the same thing
When your doctor tells you you’re “within normal range,” they’re telling you that you don’t have a diagnosable condition. There is no clinical billing code for brain fog. There is no standard of care built around “I feel flat.”
And because conventional medicine is structured around diagnosis and treatment rather than optimization, millions of women are told to just live with symptoms that are actually addressable.
That’s why Jackie uses a symptom-first approach, asking where you are in your cycle, what’s changing, what’s getting worse. Hormonal lab tests are the third guardrail to her practice.
If you want to find out the essential lab markers every woman ages 35+ should know, I found Jackie’s free guide to be very helpful.
Your ovaries age twice as fast as your biological age
By age 35, women have lost 90% of their ovarian hormonal reserve and function. Ovaries are the primary production site for testosterone, estrogen and progesterone.
More specifically, ovaries produce testosterone, and much of that testosterone is then converted into estradiol, which is the most biologically active form of estrogen.
Progesterone is what helps you sleep through the night, keeps your PMS in check, and supports mood stability. So as it starts to decline, those 2 or 3 AM night wakes I started having begin to make a lot more sense.
The Women’s Health Initiative study did a lot of damage
You may have heard that hormone replacement therapy causes breast cancer. This is one of the most consequential pieces of medical misinformation of the last few decades, and it’s still shaping how women are treated today.
Here’s what actually happened:
In the 1990s, the Women’s Health Initiative (WHI) studied whether estrogen could protect women from heart disease. They enrolled women in their 60s and 70s—many hadn’t taken estrogen for 20+ years since menopause—and put them on it. The study ended early after finding small increased risks of stroke, blood clots, and breast cancer.
The media panicked. Headlines screamed that estrogen was dangerous. Seventy percent of prescriptions were dropped overnight. Doctors stopped learning how to prescribe it, pushing women into cash-based hormone clinics with riskier compounded treatments.
But what the study actually showed was timing matters. Estrogen is heart protective—it helps prevent plaque buildup in arteries, which is one theory for why women get heart disease later than men. But once estrogen disappears and plaque accumulates, reintroducing it can destabilize existing plaques, causing the strokes seen in the WHI.
The breast cancer findings were equally misleading. The study wasn’t properly randomized for cancer risk, and some participants had previously been on estrogen. Women who developed breast cancer while on hormone therapy actually lived longer than breast cancer patients not on hormones. Breast cancer is common regardless of hormone use.
Here’s what we now know:
Estrogen when taken early protects against heart disease, anxiety, depression, breast cancer, colon cancer, cognitive decline, insulin resistance, and osteoporosis. It increases longevity—women on hormone therapy live on average three years longer than those who don’t.
What about GLP-1s?
GLP-1s blunt reward-seeking pathways, which includes food and even libido. So if you’re taking it and you’ve noticed a drop in desire or difficulty reaching orgasm, this may be why.
Jackie takes a microdosing approach in her female patients for this reason.
It’s great to manage inflammation and metabolic changes we tend to experience after age 35, but you should also closely monitor other side effects: libido, hair loss and muscle loss.
That’s why Jackie suggests pairing GLP-1 with testosterone therapy, thoughtful nutrition, strength training, and close monitoring.
Peptides: the next frontier (and the wild west)
Peptides are small chains of amino acids that act as signaling molecules. They tell your body to do something it already knows how to do, just more efficiently.
Unlike hormones, which travel everywhere and affect the whole body, peptides tend to work locally and clear quickly, which is why many are injected directly.
Two worth knowing:
GHK, a.k.a the “beauty peptide,” supports collagen production, hair follicle health, and skin. Jackie loves it compounded into a topical cream for scalp and face for microbiome optimization, hair regrowth and follicle health.
And PT-141, which we cover below under FDA-approved options, works on arousal pathways in the brain.
The catch with peptides right now is regulatory: many exist in a gray market, technically classified as research-use only, which means purity and safety testing vary wildly.
Jackie’s rule of thumb: only work with a compounding pharmacy that will hand you a certificate of analysis. If they won’t, walk away.
FDA-approved medications you may not know exist for desire and pleasure
I’ve spoken to enough women who haven’t heard of these, so I’m leaving them here, and why they matter:
Vaginal (or vulvar) estrogen: Arguably the most underused treatment in women’s health. It can prevent dryness, pain, recurrent UTIs, and even reverse the disappearance of the labia minora that happens with genitourinary syndrome of menopause. Jackie prefers a combination of estrogen and testosterone applied to the vulva, because the vulva is rich in androgen receptors. It can be used proactively, not just reactively. And it carries no breast cancer risk.
Jackie’s closing thought on this: “It’s one of the few treatments we have for anything that I can almost explicitly say is risk free. I mean, think of Tylenol. Tylenol is not risk free, right?”
PT-141 (bremelanotide / Vyleesi): Works on melanocortin receptors throughout the body and brain, improving arousal and dopamine production. Jackie describes it as more of an arousal medication than a desire one, and notes it pairs well with SSRIs (which famously suppress orgasm) and GLP-1s.
Addyi (flibanserin): Approved for premenopausal and postmenopausal women, it works directly in the brain, modulating serotonin and dopamine. It’s for women whose desire just won’t “turn on” despite being in situations where they want it to.
A note on designing for desire
Jackie is undergoing a home renovation and designing around her sexual wellness and connection to her husband. Lighting and mirrors in the walk-in closet, removing the TV from the bedroom, installing a whole-home sound system.
She even collaborated with a DJ who is also a therapist to build a 22-minute playlist calibrated to help women move from mental load to physical presence. (She got the idea from Barilla, who made pasta playlists timed to the exact minutes their pasta takes to cook. Genius.)
The underlying principle is that for women, arousal requires a transition. You can’t go from scheduling school pickups to feeling sexy without some kind of bridge. What does your bridge look like?
If you want to learn more about Jackie, follow her on Instagram and work with her here.
While we’re on the topic of perimenopause and menopause:
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In case you missed it, tune in to last week’s episode or read the highlights here:
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