Menopause is defined as starting 12 months after a woman’s  final menstrual period. “Perimenopause“ is the transition leading up to menopause and may include significant hormone fluctuations causing irregular cycles, hot flashes, sleep issues, mood swings and brain fog. Low estrogen and progesterone during menopause can cause a wide variety of symptoms since the receptors for these hormones are spread throughout the body.

Here is a breakdown of possible menopausal symptoms:

Vasomotor & Sleep 

• Hot flashes and night sweats (from estrogen’s role in temperature regulation)
• Disrupted sleep (from low progesterone). Progesterone has a natural sedative, GABA-supporting effect, so its loss alone can worsen sleep quality

Cardiovascular 

• Loss of estrogen’s protective effect on blood vessel flexibility and increased arterial stiffness.
• Higher LDL “bad“ cholesterol and declining HDL “good” cholesterol after menopause

Bone 

• Accelerated bone loss. Low estrogen speeds up bone breakdown.
• Increased osteoporosis and fracture risk, most rapid in the first 5–10 years post-menopause

Genitourinary 

• Vaginal dryness, thinning, and reduced elasticity (genitourinary syndrome of menopause)
• Increased urinary urgency, frequency, and UTI risk from thinning of urethral and bladder tissue

Brain & Mood 

• Difficulty with verbal memory and word-finding • Increased irritability, anxiety, depression
• Estrogen and progesterone both interact with neurotransmitters including serotonin and GABA.

Skin & Connective Tissue 

• Reduced collagen production, leading to thinner, less elastic skin and wrinkle formation
• Slower wound healing and increased joint/muscle pain

Metabolic 

• Shift toward central (visceral) fat accumulation, even without weight gain
• Increased insulin resistance

Other 

• Hair thinning
• Reduced libido, partly from lower estrogen and androgen levels

For decades, HRT meant synthetic estrogen and synthetic  progesterone taken orally. A landmark study called the  Women’s Health Initiative (WHI) was published in 2002  looking at the effects of synthetic estrogen/progesterone  hormone replacement in menopause. It raised alarms about  heart disease, blood clots, and breast cancer, and hormone  prescribing dropped immediately.

Since then, newer studies found that women who started  estradiol (estrogen hormone) therapy around age 50 had a  50% reduction death from all causes and no increased risk of  breast cancer. Estrogen also reduces the risk of osteoporosis  while reducing symptoms like hot flashes and night sweats.

The FDA has updated its recommendations about HRT, and  has removed the black box warning that had long made  patients and providers concerned.

Studies also show that *how* estrogen enters the body has a major impact on safety. Transdermal estrogen (patches, gels, sprays) is increasingly favored over oral tablets, particularly for women with cardiovascular or clotting risk factors.

Transdermal estrogen: Why delivery method matters When estrogen is swallowed, it travels from the gut straight to the liver before reaching the rest of the body (a process called first-pass metabolism). This flow of estrogen through the liver stimulates the production of clotting factors, inflammation, and other proteins that can raise cardiovascular risk.

Transdermal estrogen bypasses this route entirely, entering the bloodstream directly through the skin. The result is more stable hormone levels and none of the liver-driven metabolic disruption. Studies show transdermal estrogen does not increase the risk of blood clots while oral estrogen carries more than four times the clot risk. Transdermal estrogen also does not increase triglycerides the way oral estrogen does.

Estradiol, the form of estrogen used in transdermal products,  also behaves differently than the estrogens used in older  formulations. It has a more favorable effect on blood vessels,  with less impact on blood pressure and cardiovascular risk.

What about progesterone?

Women who still have a uterus need progesterone alongside  estrogen to protect against uterine (endometrial) cancer. The older hormone replacement therapy included synthetic  progesterone called progestin. The newer option is  bioidentical micronized progesterone, which has a much lower  risk of breast cancer, blood clots, and stroke. It also can act  as a mild sedative, which can help with sleep and anxiety.

Do you need labs or imaging first?

Not necessarily. Most prescribers base their HRT  recommendations on symptoms. If you report experiencing  “hot flashes”, “night sweats“, “trouble sleeping“, they will usually recommend an estrogen patch and progesterone  capsule. I would always recommend doing a comprehensive  functional test before starting HRT, just so we know exactly what your baseline numbers are and what treatment goals  should look like.

Who should be cautious with hormone replacement therapy?

HRT may not be appropriate for women with a history of  stroke, heart attack, blood clots, or breast cancer. however, the clinician can still make a clinical decision based on benefits/risk ratio of each individual. Women who are more than 10 years past menopause may also need to be cautious, as this can increase risk of cardiovascular disease.

What does HRT actually look like?

The “new normal” hormone replacement therapy usually consists of an estradiol patch and a micronized progesterone capsule. Dosages are then increased as needed to address symptoms.

Typical starting points:

Estrogen (Transdermal often preferred) 

• Estradiol patch: 0.025 mg/day (lowest patch strength), sometimes 0.0375 mg/day
• Estradiol gel: roughly 0.25–0.5 mg/day equivalent (varies by product/pump)

Progesterone (if uterus is present, or for sleep/anxiety) • Oral micronized progesterone: 100 mg/day (continuous) or 200 mg for 12–14 days/month (cyclic). Take at bedtime due to sedative effect

Vaginal estrogen (for dryness/UTI prevention) Page 5

• Much lower doses (estradiol vaginal tablet, cream, or suppository) since it acts locally with minimal systemic absorption

Testosterone cream (for libido, fat burning, energy)

How long would I stay on HRT?

The old rule was to stay on the lowest dose, shortest time, no  more than five years. This is no longer the standard. Duration is now individualized.

The Bottom Line

The strongest, most consistent evidence favors transdermal over oral estrogen specifically for reducing blood clot and cardiovascular risk. For women with elevated cardiovascular or clotting risk, transdermal delivery offers a better safety profile while providing symptom relief and bone protection. Transdermal estrogen is also better tolerated by women with a history of liver or gallbladder disease.

If you are interested in starting hormone replacement therapy, talk to your primary care provider or gynecologist about treatment options. You could also consider a virtual telehealth platform like MIDI, which specializes in menopausal hormone therapy.