Progestogen-only injections: contraception with injections

Progestogen-only injectable contraceptives are medications containing only a synthetic progestogen, administered by intramuscular or subcutaneous injection at regular intervals. The most well-known example is depot medroxyprogesterone acetate, often abbreviated as DMPA. It provides prolonged release of the hormone from a depot in muscle or subcutaneous tissue, creating a sustained contraceptive effect for several months after a single injection. [1]

Progestogen-only injectable methods primarily include DMPA, administered every 3 months, and norethisterone enanthate, administered every 2 months. In recent years, subcutaneous DMPA, which patients can self-administer after training, has become increasingly popular, reducing dependence on clinic visits and expanding access to the method in remote areas. [2]

Progestogen-only injections are highly effective and long-acting methods with a reversible effect. With proper intervals between injections, the Pearl Index is less than 1 pregnancy per 100 women per year, comparable to intrauterine systems and implants. Furthermore, this method does not require daily administration, like pills, and is not dependent on the timing of intercourse, like condoms. [3]

From a clinical perspective, progestogen-only injectable contraceptives are particularly useful for women for whom estrogen-containing methods are contraindicated or undesirable, such as those with migraine with neurological symptoms, a high risk of thrombosis, or during breastfeeding. International guidelines emphasize the important role of these drugs in the range of available contraceptive methods, particularly in family planning programs in resource-limited countries. [4]

At the same time, this method requires an honest discussion of potential downsides: irregular bleeding, possible weight gain, temporary loss of bone mineral density, and delayed fertility recovery after discontinuing injections. Updated guidelines from the World Health Organization and the Centers for Disease Control and Prevention emphasize individual risk assessment, particularly in women with risk factors for thrombosis and in adolescents. [5]

Table 1. Brief characteristics of progestogen-only injectable contraceptives

Parameter	Characteristic
Compound	Progestogen only (eg, depot medroxyprogesterone acetate)
Route of administration	Intramuscularly or subcutaneously
Interval between injections	On average 2-3 months
Type of action	Long-lasting, reversible
Main users	Women who need reliable long-term contraception
Presence of estrogen	Absent

[6]

Mechanism of action and pharmacological properties

The primary mechanism of action of progestogen-only injectables is ovulation suppression. Following depot administration of medroxyprogesterone acetate, its concentration in the blood reaches a level sufficient to sustainably inhibit the release of luteinizing hormone from the pituitary gland. As a result, ovarian follicle maturation is disrupted, ovulation does not occur, and the egg is not released into the fallopian tube. [7]

An additional important mechanism is changes in the properties of cervical mucus. Under the influence of progestogen, mucus in the cervical canal becomes thicker and more viscous, making it difficult for sperm to pass through. This creates an additional barrier to sperm entering the uterine cavity, reducing the likelihood of fertilization even in the rare cases where ovulation is possible while using this method. [8]

Progestogen also affects the endometrium. The uterine lining becomes thin, poorly prepared for implantation even if fertilization is theoretically possible. The combination of ovulation suppression, cervical mucus changes, and endometrial modification explains the high contraceptive efficacy of injectables. [9]

Pharmacokinetic depot forms create a gradual release of the hormone from the injection site. After a single administration, plasma medroxyprogesterone concentrations initially increase, then slowly decline, remaining contraceptive for approximately 12-15 weeks. A similar principle is implemented for norethisterone enanthate, with a shorter interval of action. The subcutaneous form of DMPA provides a similar profile, but with a slightly lower dose and the ability to be self-administered. [10]

Progestogen-only injectables lack an estrogen component, which distinguishes them from combination pills. This reduces the impact on blood clotting factors and the risk of thromboembolism compared to estrogen-containing methods, but new data show that in some women with an already high thrombotic risk, DMPA still requires caution and individual assessment. [11]

Table 2. Main mechanisms of action of progestogen-only injectable contraceptives

Mechanism	The essence of the process	Contribution to contraceptive effect
Ovulation suppression	Inhibition of the release of luteinizing hormone	Prevents the release of the egg
Changes in cervical mucus	It becomes thick and impassable	Makes it difficult for sperm to penetrate
Endometrial modification	The endometrium is thin and poorly suited for implantation	Reduces the likelihood of embryo implantation
Extended depot release	Gradual release of hormone from the injection site	Maintains a stable level of progestogen

[12]

Forms and application schemes

The most common form is an intramuscular injection of depot medroxyprogesterone acetate, at a dose sufficient for approximately 3 months of contraception. The drug is injected deep into a large muscle, most commonly the buttock or upper arm. The interval between injections is typically 12-13 weeks, with many guidelines allowing for a "ceiling" of up to 15 weeks without a significant reduction in effectiveness. [13]

An alternative is norethisterone enanthate, administered at intervals of approximately 8 weeks. This option is less commonly used in some countries, but remains relevant in family planning programs in a number of regions. The choice between DMPA and norethisterone enanthate depends on national guidelines, availability, and patient preference, but both methods are progestogen-only injectables. [14]

The subcutaneous form of DMPA is designed for administration of a smaller dose into the subcutaneous tissue using a special syringe or autoinjector. This allows injections to be administered not only by healthcare professionals but also by the woman herself after appropriate training, as supported by recommendations for subcutaneous self-administration of DMPA. This approach increases patient autonomy and facilitates adherence to injection schedules, especially in settings with limited access to clinics. [15]

Injectable progestogen can be started at various points during the cycle. Ideally, it's started within the first 7 days of the onset of menstruation, when the likelihood of pregnancy is minimal and the method begins working immediately. It can also be started immediately after an abortion or at a certain interval after childbirth. A "quick start" method, which starts on any day, requires the temporary addition of a barrier method and pregnancy testing. These approaches are described in detail in the Centers for Disease Control and Prevention's Selected Practice Guidelines and in the Family Planning Handbook. [16]

Adherence to the intervals between injections is critical. Delays of more than the recommended "safety period" (usually about 2 weeks for DMPA and about 1 week for norethisterone enanthate) require additional contraception and possibly a pregnancy test before the next injection. Current guidelines provide detailed guidelines for late administration, taking into account the time elapsed since the previous dose and the presence of sexual intercourse. [17]

Table 3. Main regimens for the use of purely progestogen-only injectable drugs

Preparation	Route of administration	Interval between injections	Peculiarities
Depot medroxyprogesterone acetate intramuscularly	Deep into the muscle	Around 12-13 weeks	The most common option
Depot medroxyprogesterone acetate subcutaneously	Subcutaneously	Around 12-13 weeks	Possibility of self-introduction
Norethisterone enanthate	Intramuscularly	About 8 weeks	More widely used in certain regions
Start at the beginning of the cycle	In the first 7 days	Effective immediately	Additional contraception is not needed.
"Quick Start" any day	On any day	Requires an additional barrier method	Pregnancy testing is required.

[18]

Efficiency and additional beneficial effects

According to large reviews, the Pearl Index for DMPA and other progestogen-only injectables with typical use is in the range of approximately 0.2–0.6 pregnancies per 100 women per year. This means that when the intervals between injections are observed, the method is comparable in effectiveness to intrauterine systems and implants and significantly superior to pills and condoms in normal use. [19]

Effectiveness is maintained even with long-term use, with the main causes of pregnancy being either very long delays in injections or initial administration following an undetected pregnancy. In real-world practice, most failures are due to schedule violations, so counseling on the need for timely visits or self-administration is crucial. [20]

Progestogen-only injectables also offer significant non-contraceptive benefits. Many women experience reduced menstrual blood loss, a reduction in the severity of menstrual pain, and sometimes experience amenorrhea, which many perceive as a benefit. A reduction in the symptoms of endometriosis and a reduced risk of endometrial cancer have been noted due to the prolonged progestogen effect on the endometrium. [21]

The effect on body weight remains controversial, but some studies show moderate average weight gain over several years of use, especially in younger patients. Importantly, DMPA use itself is not an absolute contraindication for overweight individuals, but it does require an honest discussion of potential weight changes and an emphasis on lifestyle. [22]

In terms of convenience, the injectable method is particularly suitable for women who find it difficult to take pills daily, who travel frequently, who live in areas with limited access to healthcare, or who prefer discreet methods of contraception. For these patients, the self-administration of the subcutaneous form further enhances the method's appeal. [23]

Table 4. Efficacy of progestogen-only injectables compared with other methods

Method	Pregnancies per 100 women-years (typical use)
Progestogen-only injectables	About 0.2-0.6
Intrauterine systems	Less than 1
implant	Less than 1
Combination tablets	About 7
Condom	About 13

[24]

Side effects, risks and safety

The most common side effect of progestogen-only injections is changes in uterine bleeding patterns. In the first few months, irregular spotting, more frequent or prolonged bleeding episodes, are often observed. Over time, many women develop amenorrhea, or complete cessation of menstruation. This is considered an expected pharmacological effect, not a pathology, provided pregnancy and organic pathology have been ruled out. [25]

Other common side effects include possible weight gain, headaches, acne, mood changes, and decreased libido in some patients. Most symptoms are mild and do not require discontinuation of the treatment, but they often lead to premature discontinuation of DMPA, as reflected in observational studies and reviews. The physician should discuss the likelihood of such effects and possible treatment options in advance. [26]

Particular attention is paid to the effect of DMPA on bone mineral density. Studies show a moderate decrease in bone density with long-term use, especially in adolescents and young women, with some of the changes reversible after discontinuation. The World Health Organization and other experts emphasize that the potential risk to bones must be weighed against the risk of unwanted pregnancy and that the method remains acceptable with informed choice and control of osteoporosis risk factors. [27]

In recent years, the possible association between DMPA use and the risk of venous thromboembolism has been revived, particularly in women with pre-existing risk factors. Updated national eligibility criteria emphasize the need for a more cautious approach to prescribing DMPA to patients with a history of thrombosis or severe thrombophilia, although the absolute risk remains lower than with combined estrogen-containing methods. [28]

Serious complications, such as severe thromboembolic events, significant allergic reactions, or significant psychiatric disturbances, are rare. Medical eligibility systems assess progestogen-only injectable methods as safe for most women, including those with multiple chronic medical conditions, when appropriately selected and monitored. [29]

Table 5. The most common side effects and their estimated clinical significance

Side effect	Frequency	Clinical evaluation
Irregular bleeding	Very often	Usually not dangerous, but can be irritating.
Amenorrhea	Often with prolonged use	Expected pharmacological effect
Weight gain	Often	Individually, requires discussion
Headaches, mood changes	Sometimes	An assessment is needed; if symptoms persist, a change in method may be necessary.
Decreased bone density	With prolonged use	Moderate, partially reversible

[30]

Medical acceptability, indications and contraindications

According to the World Health Organization's medical acceptability criteria, progestogen-only injectable contraceptives are considered methods that can be used by a wide range of women, including those with obesity, diabetes without severe vascular complications, hypertension, and other common conditions. For many conditions, DMPA is rated as a category 1 or 2 method, meaning no restrictions or some caution. [31]

Absolute contraindications include current pregnancy, severe unexplained vaginal bleeding, acute thromboembolic events, certain active cancers, and severe liver disease. In these situations, the use of DMPA and other injectable progestogens is not recommended due to the potential risk of worsening the condition or failure to control the underlying disease. [32]

Relative contraindications include the presence of risk factors for thrombosis, severe liver disease, complex lipid metabolism disorders, and some forms of migraine. Updated data, taken into account in national medical eligibility criteria and clinical guidelines, emphasize that in patients with a high thrombotic risk, the decision to prescribe DMPA should be made individually and after discussing alternatives. [33]

The main indications for the use of progestogen-only injectables are the need for reliable, long-term contraception, the desire to minimize daily activities, the inability or unwillingness to use estrogen-containing medications, and a preference for methods independent of sexual intercourse. For some women, severe dysmenorrhea or heavy menstruation is an indication, when the expected effect of reduced blood loss becomes an additional benefit. [34]

An important task for the physician is not simply to mechanically check a criteria table, but to assess the benefit-risk ratio for a specific woman. Age, body mass index, smoking status, family history of thrombosis, concomitant diseases, pregnancy plans, and preparedness for possible side effects such as amenorrhea and weight gain are taken into account. [35]

Table 6. Simplified flow chart of medical acceptability of injectable progestogens

Category by eligibility criteria	Examples of states
Category 1 (can be used)	Healthy women, obesity, mild hypertension
Category 2 (generally usable)	Smoking after 35 years, diabetes without vascular complications
Category 3 (generally not recommended)	Some severe liver diseases, severe migraine with neurological symptoms
Category 4 (contraindicated)	Current pregnancy, acute thrombosis, active breast cancer

[36]

Practical issues of application and observation

Before starting progestogen-only injectables, a thorough consultation is necessary. This includes discussion of reproductive plans for the coming years, menstrual preferences, preparedness for possible amenorrhea, attitudes toward injections, and the availability of regular medical visits or the possibility of self-administering a subcutaneous form. Risk factors for thrombosis and other contraindications are assessed. [37]

An important element is informing the patient that menstrual bleeding will likely change, and that this is not a sign of "blood stagnation" or "disease," but a typical effect of the progestogen. Family planning guidelines recommend explaining in advance to the patient the likely transition from irregular spotting in the first few months to infrequent or absent periods later, to reduce anxiety and increase adherence to the method. [38]

Monitoring includes not only reminders of the next injection date but also assessment of side effects, body weight, and, if necessary, osteoporosis risk factors. For adolescents and women with initially low bone mineral density, it is advisable to discuss the duration of use and alternatives, especially when planning use for several years in a row. [39]

Particular attention is paid to the issue of restoring fertility. After discontinuing DMPA, ovulation may not return immediately. The average time to pregnancy is approximately 10 months from the last injection, sometimes longer, as confirmed by clinical observations. Therefore, this method is not suitable for women planning a pregnancy within the next year. [40]

If severe or unusual symptoms occur—severe lower abdominal pain, suspected thrombosis, significant mood swings, severe headaches—you should immediately consult a doctor to assess the connection with the method and rule out other causes. If necessary, a change in contraceptive method is possible, but the decision is always made individually, taking into account the woman's preferences and medical indications. [41]

Table 7. Key practical points to warn the patient about

Question	Brief explanation
Changes in menstruation	Irregular bleeding at first, then possible amenorrhea
Validity period	The injection provides protection for approximately 2-3 months.
Fertility restoration	Delayed return of ovulation after cessation
The need to adhere to a schedule	It is important to arrive or get an injection on time.
Possible side effects	Weight gain, headaches, mood changes

[42]

Special patient groups

Adolescents and young women can use progestogen-only injectable methods, and the World Health Organization considers them acceptable given their impact on bone mineral density. For this group, it is particularly important to discuss the potential for weight gain, changes in menstrual cycles, and long-term impact on bone, weighing these against the high risk of unintended pregnancy at a young age. [43]

In the postpartum period, progestogen-only injectables can be used in both breastfeeding and non-breastfeeding women. International recommendations allow for the initiation of DMPA at a certain time after birth, and in breastfeeding women, progestogens have no clinically significant effect on lactation or fetal development. This is done taking into account general risk factors for thrombosis, which are elevated in the first weeks after birth. [44]

In women with chronic somatic diseases—diabetes, hypertension, obesity—progestogen-only injectable methods are often considered a safer alternative to combined estrogen-containing drugs. The absence of estrogen reduces the effect on coagulation factors and blood pressure, but an individual risk analysis remains necessary, especially in the presence of vascular complications. [45]

In patients with HIV infection, including those receiving antiretroviral therapy, DMPA and other progestogen-only injectables are considered acceptable options. Guidelines for medical acceptability emphasize the absence of significant drug interactions that would reduce contraceptive effectiveness, although the choice of a specific method depends on concomitant therapy and the woman's preferences. [46]

For women with increased thrombotic risk, prior venous or arterial thrombosis, or severe hereditary thrombophilia, new data encourage a more cautious approach to prescribing DMPA. Updated medical criteria emphasize that in this group, DMPA may be considered a category where use is generally not recommended, and preference is often given to non-rigid methods with minimal impact on hemostasis, such as copper-containing intrauterine devices or barrier methods. [47]

Table 8. Features of the use of purely progestogen-only injectable agents in special groups

Group of female patients	Key points
Teenagers	Consideration of impact on bone and body mass, high risk of pregnancy
Postpartum period	It can be used after the specified timeframes, taking into account the risk of thrombosis.
Breastfeeding women	Overall, it is an acceptable method and does not significantly disrupt lactation.
Women with chronic diseases	Often preferred over estrogen methods
Women at high risk of thrombosis	Caution is required, alternatives may be chosen

[48]

Comparison with other methods of contraception

Compared to combined hormonal pills, progestogen-only injectables offer higher efficacy with typical use because they do not require daily administration. They lack estrogen, which reduces the risk of thrombotic complications, but are associated with unique side effects such as irregular bleeding and delayed fertility. [49]

Compared to intrauterine systems (IUSs), injectable progestogens are similarly effective but require regular injections, while IUSs are implanted for several years. Intrauterine systems (IUSs) are generally better tolerated in terms of bleeding stability after an adaptation period, whereas with DMPA, irregular bleeding may persist for longer. The choice between methods depends on the woman's readiness for IUSs and her menstrual pattern preferences. [50]

Compared to implants, injectable progestogens are highly effective and require no daily intervention. The implant is implanted under the skin for several years but requires insertion and removal. Injections are technically simpler but require regular medical visits or self-administration and a delay in fertility recovery after the last dose. [51]

Unlike barrier methods such as condoms, progestogen-only injectables do not protect against sexually transmitted infections. Therefore, for women with multiple partners or a high risk of infection, the optimal strategy is often to combine injectable contraception with condom use during every sexual encounter. [52]

Thus, progestogen-only injectable contraceptives occupy an important place in the "palette" of methods as a highly effective, relatively simple, and affordable option for women whose side effect profile and injection schedule are suitable. The choice of method should always be based on an informed discussion with a doctor, taking into account medical factors and personal preferences. [53]

Frequently Asked Questions

How long after stopping injections can you become pregnant?
On average, fertility returns more slowly after stopping DMPA than after most other methods. Ovulation often returns within a few months, and the average time to pregnancy is about 10 months after the last injection. For some women, this period can be longer than a year. Therefore, this method is not recommended for those planning a pregnancy in the near future. [54]

Is it dangerous if menstrual periods become very infrequent or disappear completely?
For DMPA and other progestogen-only injectables, amenorrhea after several months of use is considered a normal and safe effect. It is associated with a strong progestogenic effect on the endometrium and the absence of ovulation. With proper assessment before use and the absence of alarming symptoms, amenorrhea is not considered a pathology and may even reduce the risk of anemia and endometrial cancer. [55]

Is it true that injectable contraception "damages bones"?
Indeed, long-term use of DMPA is associated with a moderate decrease in bone mineral density, particularly in adolescents and young women. However, studies show that some of these changes are reversible after discontinuing the method. International organizations recommend weighing this risk against the risk of unwanted pregnancy and not restricting use in most women, especially if there are no additional risk factors for osteoporosis. [56]

Is a progestogen-only injection suitable for women with excess weight or diabetes?
In many cases, yes. The absence of estrogen makes this method preferable to combined hormonal agents in obese or diabetic women without severe vascular complications. However, potential weight gain with DMPA requires consideration, and in the presence of significant vascular complications or additional risk factors, the decision is made on an individual basis. [57]

Can self-administer injections be performed?
For the subcutaneous form of DMPA, published data and recommendations confirm the safety and effectiveness of self-administration after training. Women receive instructions on injection technique, drug storage, and expiration date management. This approach reduces the number of clinic visits and increases the accessibility of the method, but requires the patient to carefully follow the instructions. [58]