Estrogen and progesterone

Perimenopause usually starts in the mid 40s, years before the last period. The first signs look like stress.

• Waking at 3 a.m. and staying awake, with or without night sweats
• Periods that close in, get heavier, then turn unpredictable
• Anxiety or a flat mood with no obvious cause
• Hot flashes, from a few a week to a dozen a day
• Vaginal dryness, pain with sex, urinary infections, less interest in sex
• Weight moving to the middle, aching joints, brain fog, thinning hair

Any two of these together, in a woman in her 40s, is perimenopause until proven otherwise. After the last period, hot flashes and vaginal symptoms take over. Bone loss and belly fat start at the same time, and you will not feel those for years.

About 1.3 million American women reach menopause each year, at a median age of 51. Eight in ten get hot flashes. The median woman has them for 7.4 years, and more than 11 if they start early in perimenopause. Vaginal and urinary symptoms affect half of postmenopausal women, and unlike hot flashes they do not fade.

• 8 in 10

  Women get hot flashes

• 7.4 years

  The median woman has them

• 1 in 2

  Women over 50 will break a bone

• 4.7%

  Postmenopausal women on treatment

Avis 2015 (SWAN). Yang and Toriola 2024 (NHANES). The Menopause Society. Bone Health and Osteoporosis Foundation.

In 1999 one postmenopausal woman in four used hormone therapy. The Women’s Health Initiative was stopped early in 2002 and use fell by more than 80 percent. That trial has now been followed for 20 years, and for women who start near menopause the results look nothing like the 2002 headlines. Those numbers are under Safety.

Your ovaries run a monthly cycle of estrogen and progesterone. In your 40s the supply of eggs runs low and the cycle turns erratic. Progesterone goes first, because it is only made after ovulation and ovulation becomes unreliable. That drives the heavier, closer periods and much of the sleep and anxiety change. Estrogen does not so much fall as swing, high then low, for years, before settling low after the last period. The swings are perimenopause. The low level is menopause.

Removing both ovaries causes menopause overnight, with harder symptoms and none of the adjustment. Chemotherapy can do the same. Menopause before 40 affects 1 to 3 percent of womenPrimary ovarian insufficiency affects about 1 percent of women by older estimates and up to 3.5 percent in recent data. Untreated it carries higher risks of heart disease, bone loss and cognitive decline. The 2024 international guideline recommends hormone therapy until at least the usual age of menopause.ESHRE, ASRM and IMS guideline, 2024, and raises the long-term risk to heart, bone and brain unless the hormones are replaced.

Estrogen fixes what low estrogen breaks. Progesterone protects the uterus and helps you sleep. Both have been tested in more women, for longer, than almost any drug in medicine.

Hot flashes and sleep go first, usually inside a month. Mood and vaginal symptoms take a little longer. Bone and metabolism change slowly and silently, and that is where most of the long-term benefit sits.

Testing. After 45 there is no blood test for menopause and you do not need one. Your symptoms and your periods make the diagnosis, because levels swing too much in perimenopause for one reading to mean anything. The first visit does include a panel to rule out what mimics menopause and to set a baseline. Thyroid, blood count, iron, metabolic panel, lipids, HbA1c, vitamin D and testosterone. We do not use saliva or urine hormone tests, which do not predict symptoms or guide dosingThe Menopause Society 2022 position statement. Salivary and urine hormone testing to determine dosing are unreliable and not recommended.The Menopause Society, 2022. Under 45, or when periods stopped early for no clear reason, we measure FSH and estradiol, because early menopause changes the plan.

Who qualifies. Any woman with symptoms that bother her, in perimenopause or after, without a reason not to use estrogen. Those are a hormone-sensitive breast cancer, a prior clot or stroke, active liver disease, or unexplained bleeding that has not been checked. Timing matters more than age. The benefits clearly outweigh the risks when treatment starts before 60 or within 10 years of the last period, and women who went through menopause early are treated at least until 51.

The hormones are the ones your body made. What differs is how they get in.

What we do not use. Pellets. They are implanted every few months and cannot be adjusted or removed. In the one direct comparison, women on pellets ran estradiol two and a half times higher384 women on pellet therapy versus 155 on FDA-approved hormone therapy. Average estradiol 238 pg/mL versus 93, with some above 1,000. Among women with a uterus, abnormal bleeding in 55 percent versus 15 percent, and hysterectomy in 20 percent versus 6 percent.Jiang et al., Menopause 2021, more than half had abnormal bleeding, and one in five ended up with a hysterectomy. The same hormones at adjustable doses do the same job without that.

Perimenopause. The first step is often progesterone alone at bedtimeOral micronized progesterone 300 mg at bedtime reduced hot flashes and improved sleep in trials, and is used cyclically or nightly in perimenopause.Micronized progesterone. It steadies sleep and calms heavy, close-together periods while estrogen is still high. When flashes, sweats or mood changes arrive, we add a low dose of estradiol through the skin. Women who still need contraception have other options and we talk through them.

Menopause. Estradiol through the skin, as a patch or daily gel, plus micronized progesterone at bedtime if you have a uterus. We start low and adjust every 4 to 6 weeks until your symptoms are controlled. The dose is set by how you feel, not by a blood level. We check a level only when the response does not match the dose, which usually means the skin is not absorbing it. Vaginal estradiol is added for dryness, pain or urinary infections, and can be used indefinitely.

Testosterone. About 4 in 10 women we see for menopause are also low in testosterone, and it is the usual reason desire does not come back on estrogen alone. When that is the case we add a low-dose cream, dosed and monitored as our testosterone article describes.

How long. As long as it is helping and the balance stays in your favour, which for most women is years. There is no age at which it has to stopThe Menopause Society 2022. Hormone therapy does not need to be routinely discontinued in women older than 60 or 65, and can be continued beyond 65 for persistent symptoms, quality of life or prevention of osteoporosis, after appropriate evaluation.The Menopause Society, 2022. We review it with you every year.

Follow-up. A telehealth check at 6 to 8 weeks to adjust the dose, then at 6 months, then yearly with a mammogram, blood pressure and bloodwork. Any bleeding after menopause is checked, every time.

Hormone therapy got its reputation from one trial. The Women’s Health Initiative was stopped early in 2002 and the headlines were breast cancer and heart attacks. The women in it averaged 63 years old, most were more than a decade past menopause, and they took oral horse-derived estrogen with a synthetic progestin. It has been followed for 20 years since.

Life expectancy. After 18 years, women who took hormone therapy were no more likely to have died than women on placebo. Women who started in their 50s were 39 percent less likely to die during the treatment yearsWHI, 27,347 women, 18-year follow-up. All-cause mortality hazard ratio 0.99 overall. Among women aged 50 to 59 at enrollment, 0.61 during the treatment years and 0.87 over the full 18 years.Manson et al., JAMA 2017.

Heart. Started within 10 years of menopause, hormone therapy roughly halved coronary heart diseaseCochrane review of 19 trials, 40,410 women. Started within 10 years of menopause, death from any cause 30 percent lower and coronary heart disease 48 percent lower. Started more than 10 years after, no benefit and stroke higher.Boardman et al., Cochrane 2015 across 19 trials. Started more than 10 years after, it did not help and raised stroke risk. That is why timing is the first question we ask.

Clots and stroke. These are risks of estrogen taken by mouth, which passes through the liver. Estrogen through the skin does not. In the largest study, patches and gels added no clot riskQResearch and CPRD, 80,396 clot cases and 391,494 controls. Oral hormone therapy raised clot risk 58 percent and oral estrogen alone 40 percent. Transdermal estrogen showed no increase, odds ratio 0.93. A separate study of 15,710 strokes found no increase with low-dose patches.Vinogradova et al., BMJ 2019; Renoux et al., BMJ 2010, and low-dose patches no stroke risk. That is why the patch is our default.

Breast cancer. In the WHI, estrogen plus a synthetic progestin added about 8 breast cancers per 10,000 women per yearWHI, estrogen plus medroxyprogesterone. Breast cancer hazard ratio 1.24 to 1.28, about 8 to 9 extra cases per 10,000 women per year. Estrogen alone, in women without a uterus, 20-year follow-up showed 22 percent fewer breast cancers and 40 percent fewer breast cancer deaths.WHI 2002; Chlebowski et al., JAMA 2020, one extra case for every 1,200 women treated. Estrogen alone, in women without a uterus, lowered breast cancer by 22 percent over 20 years. In the largest study to compare progesterone types, estrogen with natural progesterone added no risk at allE3N cohort, 80,377 women, 2,354 breast cancers. Estrogen with micronized progesterone, relative risk 1.00. Estrogen with synthetic progestins, 1.69.Fournier et al., Breast Cancer Res Treat 2008. Synthetic progestins added 69 percent. We use natural progesterone.

Everything else. Breast tenderness and some bleeding in the first months are common and settle with a dose change. Bleeding after that is checked. Fracture, diabetes and colon cancer risk all go down.

Strength training two or three times a week does more for bone, muscle and belly fat in this decade than any other habit. Protein at every meal, less alcohol, a cool bedroom and a fixed wake time all help. None of it replaces estrogen for hot flashes, and nothing over the counter comes close.