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Estradiol, progesterone and hormone therapy: what the research says

159 studies on estradiol, progesterone and hormone therapy in PMS and PMDD, each explained in plain English. 21 of them use the strongest designs: randomised trials and systematic reviews.

Randomised trial 49Survey study 28Review 24Study 22Case report 11Systematic review 9
Systematic review, 2023

What hormonal treatments have been tested for PMDD, menstrual migraine, and catamenial epilepsy?

Hormonal treatments have been tested 56 times for premenstrual mood disorder, 21 times for menstrual migraine, and 8 times for catamenial epilepsy. Combined oral contraceptives were a frequent focus.

Survey study, 2022

What causes PMS and PMDD and what new treatments are being studied?

PMS and PMDD involve changes in hormone sensitivity, serotonin levels, genetic factors, and inflammation. New treatments under research target progesterone receptors and inflammatory pathways.

Randomised trial, 2021

Does ulipristal acetate (a progesterone blocker) treat PMDD?

Yes. Women taking 5 mg daily improved by 41% versus 22% on placebo. Half achieved remission with the medication compared to 21.1% on placebo.

Study, 2021

Does ulipristal acetate help women with PMDD?

Yes. Women taking ulipristal acetate experienced improvement in irritability and depression, and half of the women achieved complete remission of PMDD.

Systematic review, 2015

What are the effects of continuous hormonal treatments for premenstrual syndrome?

The systematic overview evaluated continuous combined oral contraceptives, continuous transdermal estradiol, and continuous subcutaneous estradiol implants, but the abstract does not specify the efficacy results for each treatment.

Systematic review, 2014

Do estrogen and progesterone change how the brain processes emotions and decisions?

Yes. These hormones affect which brain areas activate when women process emotions and make decisions, particularly in areas involved in mood and choice-making. The specific pattern varies by hormone level and person.

Review, 2012

How should premenstrual disorders be diagnosed and organized?

An international group of medical experts created a unified system for defining and classifying premenstrual disorders, which separates typical PMS from more complex conditions.

Review, 2012

How is PMS diagnosed and treated, especially in women approaching menopause?

PMS affects 30-40% of reproductive-age women and responds to medications that suppress ovulation or SSRIs. Treatment must be customized to each woman's needs for contraception, PMS control, and symptom relief during the transition to menopause.

Randomised trial, 2012

Do hysterectomy or hormonal IUDs reduce premenstrual symptoms in women with heavy periods?

Both treatments significantly reduced premenstrual symptoms by 6 months with similar effectiveness. However, the study involved women treated for heavy periods, not those specifically diagnosed with PMS.

Randomised trial, 2009

Is dydrogesterone or calcium plus vitamin D better for severe PMS?

Both worked similarly, reducing symptoms by about 4.6% and 4.2% respectively, slightly better than the 3.42% reduction from placebo. The difference between the two active treatments was too small to say one is clearly better.

Systematic review, 2008

What treatments work best for PMS and PMDD?

Antidepressants called SSRIs are proven effective for severe PMDD and are the first medication to try. Lifestyle changes and exercise are recommended for all women with PMS or PMDD.

Systematic review, 2007

What treatments work for premenstrual syndrome?

Many treatments have been studied for PMS, but researchers face a major challenge: there is no standard way to measure symptom severity, making it difficult to know which treatments truly work.

Randomised trial, 2005

Does stopping ovulation help irritable bowel syndrome that gets worse during the menstrual cycle?

Yes, stopping ovulation with leuprolide acetate significantly improved bowel symptoms related to the menstrual cycle. Adding tibolone (a hormone) did not improve bowel symptoms further but did improve quality of life more than leuprolide alone.

Randomised trial, 2003

What treatments work for PMS and PMDD?

Several treatments work. Non-drug options include cognitive behavioral therapy, exercise, and supplements like calcium and magnesium. Many studies support SSRIs (taken daily or only before menstruation). Hormonal treatments that stop ovulation also help.

Systematic review, 2001

Does progesterone or progestogens help manage PMS?

No, progesterone has no clinically meaningful benefit compared to placebo, and progestogens show only a small improvement that doesn't matter in practice. This comes from a high-quality review of many randomized trials, so the conclusion is fairly reliable.

Randomised trial, 1995

Does progesterone or the anti-anxiety drug alprazolam work better for severe PMS?

Alprazolam was significantly better than both progesterone and placebo, with 37% of women experiencing a 50% reduction in symptoms. Progesterone was no better than placebo.

Randomised trial, 1995

Is a lower dose of estradiol patch as effective as a higher dose for severe PMS?

Yes. The lower 100 microgram dose was equally effective as 200 micrograms but better tolerated with fewer side effects and less dropout.

Randomised trial, 1995

Does progesterone help premenstrual syndrome symptoms?

Yes. Progesterone pessaries reduced PMS symptoms more than placebo across four cycles. However, it caused more side effects like headaches, vaginal irritation and irregular periods than placebo.

Randomised trial, 1990

Does progesterone help premenstrual syndrome?

No. Progesterone suppositories at 400 mg or 800 mg did not significantly improve premenstrual symptoms compared to placebo.

Randomised trial, 1988

Does dydrogesterone help premenstrual symptoms in real-world practice?

No, dydrogesterone was no better than placebo. While 52 percent of women on the drug improved versus 44 percent on placebo, this small difference is not clinically meaningful.

Randomised trial, 1986

Does suppressing ovulation with estradiol implants and progestin help severe premenstrual syndrome?

Yes, estradiol implants combined with cyclical progestin significantly relieved symptoms. The effect lasted throughout treatment, even though a very high proportion of placebo-treated women also improved.

Systematic review, 2025

Do drugs that stop ovulation help women with PMS?

The abstract is incomplete and does not provide the main results, so no clear answer can be determined from the information given.

Study, 2025

What causes PMS and what are the main treatment options?

The exact cause of PMS is still unknown, but inflammation and oxidative stress may be involved. Treatment typically involves lifestyle changes, vitamin and mineral support, herbal medicine, and medications, with drospirenone-containing contraceptives being the first choice.

Non-randomised trial, 2025

What treatments help PMS and PMDD?

Both medications (SSRIs, hormonal therapy) and non-drug approaches (therapy, mindfulness, supplements, herbal medicine) show promise for PMS and PMDD. More research is needed to know which works best for whom.

Review, 2025

How does progesterone affect mood and brain function?

Progesterone influences how your brain processes emotions and manages stress. In women with PMDD, targeting progesterone receptors can improve mood symptoms before your period.

Randomised trial, 2025

Does blocking progesterone change brain structure in people with PMDD?

No. A progesterone-blocking medication did not change white matter structure in the brain compared to placebo, though some secondary analyses showed differences that need further study.

Randomised trial, 2024

Does SPRM treatment change white matter volume in the brain in women with PMDD?

No. The study found no change in white matter volume with treatment, which is a fairly confident finding from a controlled trial, though the sample size was not reported in the abstract.

Randomised trial, 2021

Does ulipristal acetate help premenstrual dysphoric disorder?

Yes. After 3 months, women taking ulipristal acetate had 41% improvement in symptoms versus 22% with placebo, and 50% achieved full remission versus 21% with placebo.

Randomised trial, 2020

Does progesterone therapy help premenstrual syndrome in women with PCOS?

Yes, progesterone significantly reduced multiple emotional PMS symptoms in women with PCOS, including depression, anxiety, and mood swings.

Randomised trial, 2018

Does micronized progesterone help premenstrual syndrome?

Yes. Micronized progesterone 200 mg daily from day 16-25 of the cycle was effective for PMS, especially pain, behavior changes, and fluid retention. Treatment should continue up to 6 months to prevent relapse.

Systematic review, 2017

Do estrogen patches or gels help control PMS symptoms?

Estrogen patches and gels work by stopping ovulation and the hormone changes that cause PMS. However, the abstract does not provide results from the trials reviewed, so effectiveness cannot be assessed.

Case-control study, 2017

What cellular changes might explain why some women develop PMDD?

Researchers found that women with PMDD have abnormal differences in genes related to a protein complex called ESC/E(Z), which helps cells respond to hormones. This could explain why women develop PMDD even when their hormone levels are normal.

Randomised trial, 2013

Does progesterone reduce PMS symptoms in women with polycystic ovary syndrome?

Yes. Women with PCOS and PMS who took progesterone had significant reductions in depression, anxiety, mood swings, bloating, and several other PMS symptoms compared to placebo.

Review, 2012

Does stopping ovulation help premenstrual symptoms?

Yes, transdermal estrogen (patch, gel, or implant) can stop the cyclical hormone changes that cause premenstrual symptoms. However, women usually need monthly progestogen and may experience side effects.

Randomised trial, 2009

Which hormone add-back therapy works best with GnRH agonist for PMDD?

The lowest dose of estradiol with progesterone worked better. The highest dose (1.5mg estradiol with 400mg progesterone) actually caused more symptom recurrence than lower doses or estradiol alone.

Survey study, 2007

Is depression before a period linked to depression at menopause?

Yes. Women who were depressed premenstrually also tend to be depressed around menopause, suggesting a shared cause that may involve hormones, psychology, or both. This link held regardless of age or hormone therapy use.

Review, 2006

How do brain hormones affect PMDD and mood problems during the menstrual cycle?

Probably yes. Brain hormones that change during the menstrual cycle may trigger mood problems in PMDD by working similarly to anti-anxiety drugs. PMDD affects 2-6% of reproductive women.

Randomised trial, 2006

Do women with a history of PMS react differently to hormone therapy after menopause?

Yes. Women with a history of PMS had worse mood symptoms when progestin was added to estrogen, especially those with anxiety-related personality traits.

Randomised trial, 2006

Do women with PMDD and depression process progesterone differently than others?

Yes. Women with prior depression convert progesterone to its active form less efficiently. Women with PMDD and no depression history show unusual patterns of this conversion, suggesting altered metabolic pathways.

Systematic review, 2006

Does progesterone help treat premenstrual syndrome?

We can't be sure. While women taking progesterone improved more than those on placebo in some measures, the results were inconsistent, and only two small trials with different methods were included.

Study, 2003

Does cognitive behavioral therapy help premenstrual symptoms as well as medication?

Possibly. Growing evidence suggests cognitive behavioral therapy may work as well as medication for premenstrual symptoms and is a good option for women who prefer not to take medicine.

Randomised trial, 2003

Does natural progesterone cause mood and physical symptoms in postmenopausal women?

Yes, at a specific dose. Natural progesterone at 400 mg per day caused cyclical negative mood and physical symptoms in women without prior PMS, similar to PMS symptoms.

Randomised trial, 2003

Does leptin explain why women develop PMS symptoms?

Probably not. Leptin levels did not change with successful PMS treatment, so leptin may not be the cause of PMS.

Cohort study, 2003

How does the menstrual cycle affect women's sleep?

We cannot yet draw clear conclusions because existing studies are small and use different methods. However, sleep is almost always disrupted during pregnancy and postpartum, and menopause often causes insomnia.

Review, 2003

What role do hormones play in PMS and how should we treat it?

Female hormones trigger PMS by affecting brain chemistry, especially the serotonin and GABA systems. SSRIs and medications that stop ovulation are the most effective treatments.

Randomised trial, 2002

Do different doses of medroxyprogesterone affect mood in women on hormone replacement therapy?

Both doses caused mood symptoms, but the higher dose improved mood in women with a prior PMS history. This small randomized trial suggests lower doses do not help.

Randomised trial, 2001

Does hormone replacement therapy change serotonin receptors in postmenopausal women?

No significant change was found in serotonin transporter or 5-HT2A receptor binding with hormone treatment in healthy postmenopausal women, though depressed women showed a more pronounced effect.

Review, 2001

What medical problems can the levonorgestrel intrauterine device treat?

The levonorgestrel IUD can treat heavy periods, period pain, and prevent anemia. It may also help endometriosis pain, though this is based on a review article rather than new clinical research.

Randomised trial, 2001

Does adding tibolone to a hormone treatment help severe PMS?

Adding tibolone to leuprolide acetate (a GnRH agonist) did not reduce the hormone's benefits and may reduce hot flushes. The hormone treatment significantly improved psychological and physical PMS symptoms.

Randomised trial, 2000

Which progestin causes fewer mood problems during hormone replacement therapy?

Medroxyprogesterone caused fewer negative mood symptoms than norethindrone in women without PMS history. This randomized trial found both medications caused strong mood effects in women with a PMS history.

Review, 1999

Is premenstrual dysphoric disorder a distinct clinical disorder?

Yes, according to expert consensus. PMDD has distinct characteristics, clear symptoms linked to the menstrual cycle, and responds differently to treatment than other mood disorders.

Randomised trial, 1999

Does the drop in progesterone or stress during the menstrual cycle cause chocolate and sweets cravings?

This study found no clear evidence either way. Neither progesterone nor a tranquilizer reduced chocolate or sweets craving in women with severe PMS.

Randomised trial, 1999

Does adding estrogen and progesterone to a GnRH agonist drug improve PMS treatment?

No. Adding estrogen and progesterone actually reduced the benefit of the GnRH agonist alone for severe PMS.

Study, 1998

Which hormonal treatments work best for PMS?

Treatments that suppress ovulation generally work well for PMS. Progesterone has not been shown to work better than placebo in well-controlled studies, despite being widely promoted.

Randomised trial, 1998

Does supplementing progesterone during the luteal phase increase progesterone levels?

Yes, both dydrogesterone alone and dydrogesterone with HCG injections increased progesterone in the middle of the luteal phase compared to placebo. However, progesterone returned to placebo levels by day 11 and did not affect the premenstrual period if pregnancy did not occur.

Randomised trial, 1996

Does oral progesterone work better than vaginal progesterone for PMS?

No. Both oral and vaginal progesterone were no better than placebo for PMS symptoms, even though oral progesterone created higher levels of potentially calming metabolites.

Case-control study, 1996

What is linked to hot flushes during midlife and menopause?

Hot flushes are linked to higher FSH levels, lower estradiol, and a history of premenstrual complaints. They become increasingly common as women approach and pass their final menstrual period.

Randomised trial, 1995

Do vaginal progesterone suppositories relieve PMS symptoms?

Overall PMS scores were not significantly better with progesterone than placebo, but a specific group of 'nervous' symptoms, tension, mood swings, irritability, anxiety and lack of control, did improve significantly.

Randomised trial, 1993

Can estrogen prevent bone loss from GnRH analogue treatment?

Yes. Adding estrogen therapy prevented the significant bone loss that occurred when women took the GnRH drug Zoladex alone.

Randomised trial, 1992

Do PMS symptoms stay better after stopping progesterone suppository treatment?

Partially. Symptoms improved from baseline but worsened from the end of treatment. Only 27 percent of women were still taking PMS medications a year later.