The Science of Menopause with Dr. Mary Jane Minkin

“Any idiot can take care of menopause. It’s perimenopause that’s tricky.”

That’s how Dr. Mary Jane Minkin, clinical professor of obstetrics, gynecology, and reproductive sciences at Yale School of Medicine, kicks off our conversation. And she’s not wrong.

Menopause affects half the population, yet it remains one of the most misunderstood and under-discussed phases of women’s health. Confusing symptoms, fluctuating hormones, cultural myths, and decades-old controversies (hello, WHI study panic) have left many women unsure of what’s happening in their bodies—and where to turn for answers.

That’s why Dr. Catherine Isaac, Thrive Wellness Physician, and Dr. Mary Jane Minkin sat down to unpack what’s really going on during menopause and perimenopause—from shifting hormones and symptom variability to the truth about hormone therapy.

The Perimenopause Puzzle & Symptoms Unpacked

When it comes to menopause, the word timing can feel slippery. Ask ten women when perimenopause started for them, and you’ll likely hear ten different answers. According to Dr. Minkin, that’s exactly the point.

“Perimenopause is the trickiest part. It’s hard to define, and it’s even harder to pin down exactly when these changes are occurring,” she explains. “One day your ovaries might not be working at all, the next they’re working double-time. A single blood test isn’t enough to capture that rollercoaster.”

This hormonal unpredictability means that perimenopause isn’t a single moment, it’s a transition. And it’s why women can feel so different, even when they’re the same age or technically at the same stage of life.

When Dr. Isaac asks about symptoms, Dr. Minkin is quick to point out that menopause is far more than the stereotypical hot flash. “Hot flashes are the classic complaint here in the U.S., but symptoms can vary by populations,” she notes. For example:

• In the U.S., hot flashes and sleep disturbances top the list.
• In the Philippines, achiness is the leading complaint.
• The SWAN study (Study of Women’s Health Across the Nation) shows that hot flashes can last an average of 7.4 years—but closer to 10 years for African American women, and just under 5 years for Asian women.

Beyond hot flashes, women often report:

• Vaginal dryness and irritation
• Urinary symptoms or recurrent infections
• Decreased libido (sometimes from discomfort, sometimes unrelated)
• Achiness or joint pain
• Mood changes, brain fog, and forgetfulness
• Sleep disruption (with or without hot flashes)

And then there’s the brain. “Yes dear, it is in my head,” Dr. Minkin quips, recalling a favorite line she coaches patients to say to dismissive partners. “Right in my hypothalamus here, which is right behind the bridge of my nose.” That's where all of these chemical changes are occurring, which are reflecting the sudden drop in estrogen levels.

In other words: menopause doesn’t look the same for every woman. And that’s exactly why recognizing the wide spectrum of symptoms matters for patients and for the providers who may be overlooking them.

Hormones, Heart, Bones & Brain: What’s Really Happening

When menopause begins, estrogen levels don’t slowly fade—they fall fast. “The average age of menopause is 51,” Dr. Minkin explains. “You can go through menopause at 35, you can go through it at 60, but on average it’s 51. Estrogen production goes down precipitously.”

Testosterone changes, however, are more gradual. “Our ovaries make testosterone too,” she says. “That decline is more gradual. On average, it goes on for another 10 or 12 years after menopause, so even five or six years after your last period, your ovaries are usually still making some degree of testosterone, albeit less than they made five or six years ago in general.” She also notes that the adrenal glands continue to make DHEA, which can convert to estrogen or testosterone, making the picture more complex.

🫀 The Cardiovascular Shift

Falling estrogen affects more than just hot flashes. “Our HDL, the good cholesterol, goes down. The bad cholesterol, LDL, goes up, and triglycerides usually go up,” Dr. Minkin says. “Estrogen acts as a vasodilator. It helps blood vessel walls relax. When that goes away, blood pressure goes up because the vessels aren’t as compliant as they used to be.”

Some weight gain can happen, too. “If someone comes up to me and says, ‘I hate menopause because I gained 40 pounds,’ that’s probably not all menopause,” she clarifies. “But basal metabolic rate does go down, and people don’t like that.”

🦴 Bones & Brain

Estrogen plays a critical role in bone and brain health. Without it, bone density declines, increasing osteoporosis risk. And for women who go through menopause early—whether naturally or through oophorectomy—the stakes are even higher. “If you have your ovaries removed before 45 and don’t take estrogen therapy, your chance of getting dementia later in life is threefold increased, and your risk of heart disease goes up sevenfold,” she says, referencing Mayo Clinic data.

🧪 The WHI Study: A Turning Point

The conversation inevitably turns to the Women’s Health Initiative (WHI) study and the fallout that reshaped menopause care. The WHI followed the Nurses’ Health Study, which had suggested estrogen therapy might protect the heart. But in July 2002, the estrogen-plus-progestin arm of the WHI was stopped early after a small increase in breast cancer risk was flagged.

“It was a day that will live in infamy,” Dr. Minkin recalls. “The minute they heard something might increase breast cancer risk, women panicked. They flushed their estrogen tablets down the toilet.”

The nuance was lost: the risk increase was very small, and the estrogen-only group actually showed a decreased risk of breast cancer. Still, the media frenzy led to plummeting hormone therapy use and, as Dr. Minkin points out, “medical schools and residency programs basically stopped teaching menopause management.” The ripple effects of that moment are still felt today.

Treatment: Timing, Options & Myths

One of the biggest shifts in menopause care over the last two decades has been around when to start treatment and what kind of treatment to opt for. According to Dr. Minkin, timing matters more than many people realize.

“If there’s a gap between going through menopause and starting hormone therapy—say, 12 or 13 years—you may not get the cardiovascular benefits, and in some cases it might even increase risk,” she explains. “That’s why we talk about the critical timing hypothesis. We want to start closer to menopause, not decades later.”

🩺 Who Shouldn’t Use Hormone Therapy?

Dr. Minkin notes that while estrogen therapy is safe for many, there are some important contraindications:

• A history of blood clots, stroke, or thromboembolic disease
• Migraine with aura
• Gallstones (oral estrogen can aggravate the gallbladder)
• Unexplained vaginal bleeding (which must be evaluated before starting therapy)
• Certain estrogen receptor–positive cancers, particularly active breast cancer

“Estrogen can increase clotting risk,” she says. “Pills do it more than patches or gels, because when you swallow a pill it goes through the liver and stimulates clotting factors. With transdermal forms, the risk is much lower.”

💊 Therapy Options

Dr. Minkin breaks down the main approaches:

• Oral Estrogen: Easy to take and common, but slightly higher clot risk.
• Transdermal Estrogen (patches, gels, or vaginal ring): “Transdermal doesn’t have that same clotting risk,” she notes. It’s often preferred for women with migraines or higher cardiovascular risk.
• Vaginal Estrogen: A local treatment for genitourinary symptoms. “The amount absorbed is minuscule,” she says. Both the Menopause Society and ACOG support its use even in breast cancer survivors, though some oncologists remain cautious. “The problem is the package insert is the same as systemic estrogen, so people get scared,” she adds, referencing ongoing advocacy to update labeling.

For women with a uterus, progesterone or a progestin is added to protect the uterine lining. 

“Think of estrogen as the fertilizer and progesterone as the lawnmower,” she says, quoting a colleague. Natural micronized progesterone tends to be better tolerated than older synthetic progestins and has a bonus: “It helps people sleep,” she adds. For some, a progesterone IUD offers a convenient, localized option.

Final Thoughts

Talking with Dr. Mary Jane Minkin makes one thing clear: menopause isn’t a mystery—but decades of misinformation have made it feel that way.

Here are a few key insights from our conversation:

• Perimenopause is complex and highly individual. Hormonal fluctuations can’t be pinpointed with a single test, and symptoms vary widely across women, cultures, and timelines.
• Menopause affects more than hot flashes. From brain fog and sleep changes to cardiovascular shifts and bone density, its impact spans multiple systems.
• Hormone therapy, when timed and tailored, can be safe and effective. Starting closer to menopause offers the best cardiovascular outcomes, and transdermal or localized options provide flexibility for different needs.
• Misinformation still matters. The WHI study’s media fallout reshaped medical training and patient decisions for decades — but today, we know much more.

“If you have your ovaries removed before 45 and don’t take estrogen, your risk of dementia triples and your risk of heart disease goes up sevenfold,” Dr. Minkin reminds. “These are serious issues — and we want women to have accurate information.”

This article is for informational purposes only and does not constitute medical advice. The information contained herein is not a substitute for and should never be relied upon for professional medical advice. Always talk to your doctor about the risks and benefits of any treatment.