Medroxyprogesterone is a synthetic form of progesterone used primarily for birth control, managing abnormal uterine bleeding, treating missed periods, and protecting the uterine lining during menopause hormone therapy. It comes in two main forms: oral tablets (sold as Provera) and an injectable shot (sold as Depo-Provera), and each form serves different purposes.
Birth Control Injection
The most widely recognized use of medroxyprogesterone is the Depo-Provera shot, a long-acting contraceptive injection given once every 13 weeks. It works through three overlapping mechanisms: it stops ovulation by suppressing the hormonal surge that triggers egg release each month, it thins the uterine lining to make implantation unlikely, and it thickens cervical mucus so sperm can’t easily reach the egg.
A lower-dose version called Depo-SubQ Provera 104 is injected just beneath the skin rather than deep into muscle. Both versions require consistent timing. If you go longer than 15 weeks between shots, you may need a pregnancy test before the next one and should use backup contraception for seven days afterward.
Abnormal Uterine Bleeding and Missed Periods
Oral medroxyprogesterone tablets are FDA-approved for two specific menstrual conditions: abnormal uterine bleeding caused by hormonal imbalance (not by fibroids or other structural problems) and secondary amenorrhea, which is the absence of periods in someone who previously had them. In both cases, the drug works by acting on the uterine lining. It shifts the lining from a growth phase into a more stable, secretory phase. When treatment stops, the lining sheds in a controlled way, producing a withdrawal bleed that essentially resets the cycle.
Uterine Protection During Menopause Therapy
For postmenopausal women taking estrogen to manage symptoms like hot flashes and vaginal dryness, medroxyprogesterone plays a protective role. Estrogen alone stimulates growth of the uterine lining, which over time raises the risk of endometrial hyperplasia, a precancerous thickening. Adding medroxyprogesterone counteracts that growth. This combination is only necessary for women who still have a uterus.
Two common dosing approaches exist. In the continuous method, a small daily dose of 2.5 mg is taken alongside estrogen every day, often combined into a single tablet. In the cyclical method, a higher dose of 5 to 10 mg is taken during the first 10 days of each month alongside daily estrogen. The cyclical approach tends to produce a monthly withdrawal bleed, while continuous dosing often leads to irregular spotting that typically fades over several months.
Endometriosis Pain
Medroxyprogesterone is also used off-label to manage pain from endometriosis, a condition where tissue similar to the uterine lining grows outside the uterus. Higher doses suppress the hormonal environment that fuels these growths. In clinical research, the injectable form reduced pain intensity by about 53% over six months. That’s a meaningful improvement, though it comes with trade-offs: menstrual irregularities, weight gain, and breast tenderness are common at the doses needed for pain control.
How It Works in the Body
Medroxyprogesterone binds to progesterone receptors in the brain and reproductive tract. In the brain, it dials down the release of gonadotropin-releasing hormone, which is the signal that normally tells the ovaries to mature and release an egg each month. Without that signal, ovulation doesn’t happen. In the uterus, it transforms the lining from an actively growing state to a quieter one, which is why it’s useful for both contraception and controlling heavy or irregular bleeding.
Bone Density and Long-Term Use
The injectable form carries an FDA boxed warning, the most serious type, about bone mineral density loss. The shot lowers estrogen levels, and estrogen is essential for maintaining bone strength. In clinical studies, women using the injection for up to five years lost an average of 5 to 6% of bone density in the spine and hip, compared to no significant change in women not using it. The loss was steepest in the first two years, with smaller declines after that.
After stopping the injection, bone density partially recovers over about two years, but the recovery may not be complete, especially for women who used it for longer periods. This is particularly relevant for teenagers and young adults, because those years are when the body builds its lifetime peak bone mass. The FDA recommends limiting use beyond two years unless other contraceptive methods aren’t suitable. For women who do continue long-term, periodic bone density evaluation is advised.
This concern applies specifically to the injectable form. The oral tablets are used at much lower doses and for shorter durations, so they don’t carry the same warning.
Common Side Effects
The side effects you’re most likely to notice depend on which form you’re taking. With the injection, irregular bleeding is the most common experience, especially in the first few months. Some women have frequent spotting, others have prolonged bleeding, and many eventually stop having periods altogether. Weight gain is another well-documented effect, though the amount varies widely from person to person.
With the oral tablets, side effects tend to be milder because doses are lower and treatment courses are shorter. Breast tenderness, bloating, mood changes, and headaches are the most frequently reported. These typically resolve once the course is finished.
Fertility After Stopping the Injection
One practical detail that catches many people off guard is how long fertility takes to return after stopping the Depo-Provera shot. Because each injection is designed to last about 15 weeks, the medication doesn’t clear immediately. Research from a large study in Thailand found a median delay to conception of about 9 months after the last injection. That’s the total time including the residual effect of the final shot plus the body’s own recovery period. Some women conceive sooner, others take longer, but this timeline is substantially slower than what you’d expect after stopping birth control pills or removing an IUD, where the median delay is closer to 4 to 5 months.
If you’re planning a pregnancy in the near future, this delay is worth factoring into your timeline. It doesn’t mean the shot causes permanent infertility; it means the hormonal suppression takes months to fully wear off.