Menstrual Suppression

Anatomy and Physiology

Phases of the Menstrual Cycle

Menstrual cycles are described relative to the onset of menses (ie, the shedding of the endometrial lining), with cycle day 1 being the onset of any menstrual bleeding. The menstrual cycle is primarily divided into the follicular and luteal phases.[6] Since the biological reproductive cycle comprises physiologic cyclic changes in the ovary and the endometrium, the 2 primary phases of the reproductive cycle are characterized according to the physiologic effects in both regions.

The first phase, known as the follicular phase in the ovarian cycle or the proliferative phase when describing the endometrium, begins at the onset of menses and continues until ovulation, day 1 to day 14 in an average 28-day menstrual cycle. The second phase, known as the luteal phase in the ovarian cycle and the secretory phase in the endometrial cycle, occurs on cycle days 14 to day 28, from ovulation until the onset of the next menses. These cycles are regulated by the interplay of estrogen, progesterone, follicular stimulating hormone (FSH), luteinizing hormone (LH), and gonadotropin-releasing hormone (GnRH) within the hypothalamic-pituitary-ovarian (HPO) axis.

Menstrual Cycle Physiology

In the follicular phase, GnRH pulses trigger the anterior pituitary gland to release FSH, which stimulates ovarian follicles to mature and produce estrogen. This estrogen stimulates the growth of the endometrium, and FSH levels begin to decline due to feedback inhibition at the pituitary level. As FSH levels decrease during the follicular phase, most developing follicles undergo atresia, and typically, a single dominant follicle persists. At the end of the follicular phase, estrogen's effect on the pituitary switches from inhibitory to stimulatory, resulting in a surge of LH from the pituitary, triggering ovulation.

After the release of the oocyte and under stimulation from LH, the now-empty follicle is transformed into the corpus luteum, which begins secreting progesterone. Generally, natural progesterone causes maturation and stabilization of the endometrium. While the follicular phase may last a variable amount of time until a follicle matures and ovulation occurs, the persistence of the corpus luteum, and thus the luteal phase, is generally much more consistent in duration, lasting about 2 weeks. If pregnancy does not occur within the first few days after ovulation, estrogen and progesterone levels decline in the second half of the luteal phase, approximately days 21 through 28. This hormone decrease ultimately triggers menses.[6] Without exogenous hormones, periodic menses are essential to prevent endometrial hyperplasia.

Menarche and Adolescent Menstrual Cycles

The onset of menstruation, or menarche, typically begins between 10 and 15 years of age.[6][7] Biologically female adolescents are at high risk for menstrual dysfunction due to immaturity of the HPO axis, resulting in anovulatory cycles, particularly in the first 2 years postmenarche.[8][9] Anovulatory cycles are associated with irregular cycle length, ranging from 20 to 90 days, and heavy or prolonged menstrual bleeding.[10] Despite adolescents being more likely to have anovulatory cycles with overall longer cycles, up to 90% of cycles are between 21 and 45 days long.[7] As the HPO axis matures over 1 to 2 years postmenarche, ovulation and the menstrual cycle tend to become more regular. By the third year of postmenarche, 60% to 80% of adolescents have 21- to 34-day cycles, comparable to adults with regular menses.[7][8]

Physiologic Mechanisms of Medication-Induced Secondary Amenorrhea

Suppression or cessation of menses is achieved by inducing significant structural changes to the endometrial lining through glandular atrophy or decidualization. Combined hormonal contraceptives (CHCs), which include estrogen and progestin (eg, OCPs, the transdermal patch, and the intravaginal ring), DMPA, or hormonal LARCS, can prevent the growth of the endometrium in 2 significant ways.

First, CHCs and DMPA inhibit the release of FSH and LH within the HPO axis; the suppression of FSH decreases estrogen, depriving the endometrium of its primary "growth factor."[11][12] Secondarily, synthetic progestins do not have the same effects on the endometrium as natural progesterone. Synthetic progestins tend to be more androgenic, and continuous exposure generally leads to endometrial glandular atrophy.[13] These progestins are found in CHCs, progestin-only pills, levonorgestrel-releasing intrauterine devices, and etonogestrel implants. DMPA also suppresses menses by causing decidualization of the endometrium and inhibiting gonadotropin secretion from the pituitary.[14][15] 

Given these mechanisms of action, little endometrial tissue growth occurs within the uterus with contraceptive use. Bleeding that occurs is secondary to hormonal withdrawal or breakthrough bleeding due to a "fragile" atrophic endometrium rather than true physiologic shedding of the endometrial lining.[3][4][12] The classic use of a placebo week with OCPs to precipitate withdrawal bleeding to mimic the natural lunar cycle of menses is a historical remnant based on the social and cultural norms of women during the era in which hormonal contraceptives were developed. The placebo week is not based on biological need, nor is it required for health.[3][4][12]

By causing endometrial atrophy, menstrual suppression may also be beneficial in treating heavy menstrual bleeding, dysmenorrhea, endometriosis, and menstrual-related blood loss in bleeding diathesis. (Please refer to the Indications section for more information).[3][5][12] Evidence suggests contraceptive use protects against endometrial, ovarian, and colorectal cancers, as described in a 2017 study of 46,000 women, specifically using OCPs.[16] 

Upon discontinuation of CHCs, DMPA, or hormonal LARCs, normal HPO axis function returns and endometrial growth resumes, though this may take several months.[11][17] Additionally, a 2018 systematic review and meta-analysis of over 14,800 women concluded no evidence of impact on baseline fertility with either the use of IUDs or long-term contraception use. The pregnancy rate within 12 months of contraception discontinuation in this review was 83%, only slightly lower than that of nonhormone users who had rates of 85% to 94%. The study authors theorized this was due to the temporary delay in the return of ovulation following hormonal contraceptive discontinuation.[17] Long-term fertility rates are typically not affected.[3] Each suppression method's administration, indications, and efficacies vary, and selection should be individualized to the patient's needs. (Please refer to the Techniques section for more information) Special populations could benefit from menstrual suppression as well.

Menstrual Symptoms Management

Menstrual-related symptoms, including heavy menstrual bleeding, dysmenorrhea (ie, excessive pain associated with menses), and premenstrual syndrome, impact up to 2.5 million biological women annually and may lead to absenteeism from school or work and decreased participation in social, athletic, professional, or recreational activities.[4][18] Therefore, individuals may prefer to suppress menses to decrease the burdens of pain, bleeding, and other symptoms (eg, bloating, fatigue, and mood changes). Some individuals may also desire to control menstrual timing rather than experiencing regular monthly or irregular menses.[2][4][5][12] 

Several studies suggest that individuals may prefer to delay, suppress, or completely stop their period for an improved quality of life, including up to 65% of female college students and up to 86% of female military personnel.[12][19][20] The greatest desire for suppression is observed in the youngest and oldest menstruating individuals compared to median-aged reproductive individuals.[21] This preference varies between global regions, with a higher preference for amenorrhea in North America, South America, and Europe and a lower preference in the Middle East and Africa.[12][21]

Management of Comorbid Conditions

Menstrual suppression may also be utilized for other health conditions, including managing endometriosis, decreasing blood loss related to bleeding diathesis, particularly von Willebrand disease, and reducing the risk for or worsening existing anemia.[3][5][12] Up to 15% of iron deficiency anemia diagnoses are associated with menstrual disorders and abnormal bleeding. Consequently, achieving amenorrhea improves iron levels in menstruating individuals.[19]

Burdens of Menstrual Hygiene

Decreasing menstrual hygiene's contribution to global inequality and environmental degradation is also important. Approximately 800 million individuals menstruate on any given day, requiring them to have reliable access to menstrual hygiene products (eg, pads, tampons, menstrual cups, or panties), clean water, and private sanitation facilities.[1] Unfortunately, many people around the world who menstruate do not have access to these resources, a global inequity deemed "period poverty," which may contribute to a disproportionately higher rate of school or work absenteeism, embarrassment, social ostracization, and risk for vaginal or urinary tract infection.[1][4] 

If access to menstrual suppression options can be achieved and the number of bleeding days decreased, these burdens on populations with period poverty can be reduced. For example, in well-developed countries, an individual without a reliable income may have access to hormonal contraceptives through a government-sponsored health plan but may lack dedicated funds to purchase menstrual hygiene products. Additionally, several populations may face unique challenges associated with menstrual hygiene, including deployed military members, people working in remote locations, those with housing insecurity, or incarcerated individuals.[3] Menstrual hygiene products are also associated with significant monetary costs and environmental waste. Decreasing bleeding days may assist in lowering this personal cost and reduce the global environmental impact of single-use synthetic materials used and disposed of during menses.[1]

Special Populations

Adolescents

Adolescents are at high risk for menstrual dysfunction, especially in the first 1 to 2 years postmenarche.[8] According to recommendations, clinicians caring for adolescents should discuss pubertal development and menarche during annual wellness exams starting as early as age 8.[7]. Due to anovulatory cycles, adolescents are prone to variable cycle lengths, heavy menstrual bleeding, and prolonged menstrual bleeding.

Adolescents, with or without the involvement of a parent or caregiver, may opt for menstrual suppression for several reasons. Menstrual suppression may be useful in helping regulate the HPO axis and prevent highly irregular cycles and associated stress.[22] Adolescents, like adults, may desire menstrual suppression to decrease menstrual-related symptoms (eg, pain, bloating, and fatigue). They may also wish to decrease their menstrual hygiene burdens while attending school, where access to menstrual hygiene supplies can be difficult or be accompanied by social stressors or embarrassment. Additionally, adolescents often desire control over the timing of menses for special events (eg, camp, graduation, travel, competitive sporting events, or entire sports seasons).[4][22] Menstrual suppression has also been proposed as a management adjunct for adolescents with chronic headaches, particularly if the headaches occur near the time of menses.[22] The American Academy of Pediatrics (AAP) does not recommend a routine pelvic exam before initiating menstrual suppression in individuals aged younger than 21 if normal menstruation occurs.[23] 

Patients with Developmental or Physical Disabilities

Ideally, before menarche, clinicians should discuss menses and menstrual management with individuals with developmental or physical disabilities and any caregivers.[24][25][26] Clinicians must understand the individual's or caregiver's motivations for menstrual suppression and establish clear expectations and treatment goals while maximizing patient autonomy based on their cognitive abilities.[24][26][27][28] Clinicians should not initiate menstrual suppression before menarche to ensure the appropriate onset of menarche and pubertal development.[25][29] However, anticipatory guidance for patients and caregivers can help reduce anxiety regarding menstruation.

A 2021 retrospective cohort study of adolescents and young women with disabilities found that the primary reasons for seeking menstrual suppression were irregular menstrual bleeding, heavy menstrual bleeding, hygiene burden, inconvenience of menses, dysmenorrhea, and assistance in managing comorbid conditions (eg, behavioral issues and catamenial epilepsy).[30] Caregivers, however, are often primarily concerned with hygiene burdens, menstrual-related symptoms, and management of difficult behavior.[25][31] Quality of life, school attendance, participation in recreational and social activities, and pregnancy prevention should also be considered.[25] 

Furthermore, before initiating menstrual suppression, the individual's medical and menstrual history should be considered to evaluate for and rule out underlying metabolic, hormonal, or other pathology that may contribute to menstrual dysfunction. Medication reconciliation is also key in this population. Some medication classes frequently utilized in the setting of developmental or physical disabilities can have significant drug interactions with hormonal contraceptives.[27][25][29] (Please refer to the Contraindications section for more information). For example, enzyme-inducing antiepileptic drugs interact with all estrogen-containing methods, as well as with oral progestins.[25]

Other considerations include a patient's mobility, ability to swallow pills, cognitive ability to understand menses, and menstrual hygiene. For instance, when individuals have limited mobility, relevant issues include the risk of venous thromboembolic events (VTE), lower bone mineral density, and increased difficulty with mobility due to weight gain. Therefore, the AAP recommends careful individual assessment and shared decision-making to determine the most appropriate menstrual suppression method for patients with disabilities.[25] Moreover, clinicians should evaluate pregnancy and sexual abuse risks in individuals with developmental or physical disabilities before initiation of menstrual suppression.[25][32]

Transgender and Gender-Diverse Individuals

In transgender and gender-diverse adolescents and adults, menses can be a significant source of distress; therefore, menstrual suppression may be an important intervention in gender-affirming care.[33][34] Menstrual suppression, which may begin before menarche in this select population, should be initiated with an interprofessional team.[29][35] (Please refer to the Enhancing Healthcare Team Outcomes section for more information).

Understanding the motivation for and the desired outcome of menstrual suppression is essential to guide the treatment decisions. Often, the goal is to achieve complete amenorrhea to help reduce menstrual-related gender dysphoria, though individuals may also desire contraception or management of menstrual-related symptoms.[33] GnRH agonists and testosterone are commonly selected in this setting, particularly when patients prefer a non-estrogen-containing option; however, these medications alone are not adequate forms of contraception.[29][36]

Military Personnel and Athletes

As of 2020, nearly 17% of US Army service members are biological women, and as of 2016, all combat jobs are open to both male and female individuals.[19] Unique challenges are faced by menstruating military personnel, including operational assignments with high levels of stress, travel and performance demands, unclean field environments, limited access to adequate sanitation facilities or hygiene products, lack of privacy, difficulty conducting hygiene due to required body armor or other equipment, and the inconvenience of bleeding and other menstrual symptoms in the field and deployed environments.[2][19][37]

Therefore, up to 86% of menstruating military personnel report a desire for amenorrhea during deployment. However, as few as 7% utilize menstrual suppression methods, and only a third report being counseled by a clinician regarding menstrual suppression options.[2][19] Menstrual suppression may be beneficial in decreasing menstrual-related burdens on service members and improving the military force's health and readiness.[19] 

Competitive athletes may face similar challenges in managing menses, including the need for high performance, elevated stress levels, frequent travel, and the inconvenience of menstrual symptoms during competition. Menstruating athletes may choose to manipulate or suppress their menstrual cycle to maximize performance.[3][4] In these populations, clinicians must carefully consider the effects of continuous hormonal contraceptive use on bone health and the risk of bone stress injury due to the higher risk of low bone mineral density (BMD) and fractures.[37][38] (Please refer to the Complications section for more information).

Active Malignancy

Individuals with active malignancy are at risk of thrombocytopenia due to the malignancy, chemotherapy, radiation, or stem cell or bone marrow transplantation.[27] Thrombocytopenia can result in heavy menstrual bleeding in approximately 40% of patients undergoing cancer treatment, potentially leading to the need for transfusion, hospitalization, or delay in cancer treatment.[27] Therefore, clinicians should discuss menstrual suppression before starting cancer treatments in menstruating individuals.[27] 

Patients with malignancy will most likely require a progesterone-only method (eg, progestin-only pills or LARC) or a GnRH agonist for suppression, as estrogen-containing products are generally contraindicated in individuals with a high risk for thromboembolism (Please refer to the Contraindications section for more information).[4][27] Despite this, the US Medical Eligibility Criteria classifies CHCs as category 1, with no restrictions for use, in the setting of endometrial and ovarian cancers awaiting treatment, due in part to the fact that pregnancy would increase a patient's overall risk and definitive surgical treatment of these cancers obviates the need for further menstrual suppression.[39] 

Notably, CHCs are contraindicated in patients with a current or prior breast cancer history.[40] (Please refer to the Contraindications section for more information). GnRH agonists, primarily leuprolide acetate and triptorelin, are preferred for patients who are adolescents and undergoing cancer treatment due to demonstrated amenorrhea rates as high as 96%.[29] However, clinicians should ensure that patients are aware that GnRH agonists are not sufficient for contraceptive purposes. In these patients, barrier methods or a copper IUD are frequently recommended.[40]

Indications

Menstruating individuals or their caregivers may choose to pursue menstrual suppression for personal or medical reasons. Notably, a study revealed that as many as 59% of women in the US expressed a desire to eliminate their monthly menstrual periods.[41] For the average adult female, reasons for suppression include decreasing bleeding, pain, and other perimenstrual symptoms, improving quality of life, managing certain medical conditions, lowering the burdens of menstrual hygiene, and decreasing the use of disposable hygiene products.[4][5] 

Contraindications

Contraindications to menstrual suppression align with the general contraindications for each hormonal contraceptive agent.

Estrogen-Containing Contraceptive Contraindications

Estrogen-containing contraceptives are contraindicated in the setting of medical comorbidities that may increase the risk of thromboembolism, including:

• Hypercoagulable disorders (eg, Factor V Liden deficiency)
• Active liver disease
• Migraine with aura
• Active smoking (particularly if older than 35)
• Valvular heart disease
• Diabetes with vascular sequelae
• Peripheral or cerebrovascular disease
• Prior history of pulmonary embolism, deep venous thrombosis, or stroke [4] 

Additionally, estrogen-containing contraceptives are contraindicated in the setting of current or prior history of some hormone-sensitive cancers, especially breast cancer, due to the risk of cancer recurrence or growth stimulation.[27][39] In the case of ovarian and endometrial cancers, however, the US Center for Disease Control and Prevention's Medical Eligibility Criteria state that CHCs are acceptable options while awaiting treatment.[39] Care should be taken in balancing the risks of thromboembolism with the risks of pregnancy while awaiting cancer treatment.[42][43] These methods are also contraindicated in uncontrolled hypertension or known coronary artery disease due to the risk of worsening hypertension and increasing risk for adverse cardiovascular events, respectively.[4][27] Patients should be counseled on progesterone-only alternatives, which are safer and equally effective.

Progestin-Only Contraceptive Contraindications

Progestin-only pills have very few contraindications; the primary absolute contraindication is active breast cancer. Use is also relatively contraindicated in patients with systemic lupus erythematosus (SLE) with antiphospholipid antibodies, severely decompensated cirrhosis, liver tumors, and a history of bariatric surgery with malabsorptive procedures.[39]

Levonorgestrel-releasing IUD is contraindicated in patients with uterine abnormalities (eg, septate or bicornuate uterus), active genitourinary infection, and current breast, endometrial, or cervical cancer.[4][39] Initiating use is also relatively contraindicated in patients with SLE with antiphospholipid antibodies, complicated solid organ transplants, and severely decompensated cirrhosis.[39]

Injectable medroxyprogesterone acetate is relatively contraindicated in patients with low bone mineral density (BMD), risk factors for BMD loss, or high risk for low BMD sequelae, including athletes or military personnel with high-volume weight-bearing physical activities, previous bone stress injury, athletes with low energy availability, nutritional deficiencies, those who are middle-aged, chronic steroid use, or immobility.[15][37][38] Injectable medroxyprogesterone acetate is also relatively contraindicated as a first-line agent in adolescents who have not yet reached peak bone mass within the first few years after menarche.[22] Though the rate of BMD accumulation increases significantly at the beginning of puberty but rapidly decreases approximately 2 years after menarche, ACOG and the World Health Organization do not recommend DMPA age restrictions as the benefits outweigh the theoretical risks. However, clinicians should counsel adolescents regarding DMPA risks and other contraceptive methods available that do not affect BMD.[15] 

Anticonvulsant Medication Interactions

Special consideration should be taken when selecting a menstrual suppression method for patients prescribed anticonvulsant medications due to their known interactions with systemic CHCs and oral progestin-only pills (POPs). Many anticonvulsants and other neuropsychiatric medications, including phenobarbital, phenytoin, carbamazepine, and, to a lesser extent, topiramate, induce the hepatic cytochrome P450 system and interfere with contraceptive efficacy and cycle control reliability.[25][29][44] As a result, systemic CHCs may result in irregular bleeding, and higher doses may be required to achieve amenorrhea.[44]

The CDC Medical Eligibility Criteria for Contraception categorizes the estrogen-containing methods and the progesterone-only pill as category 3 (ie, risks outweigh the benefits) for use concurrently with enzyme-inducing anticonvulsant agents.[39] In general, hormonal contraceptives do not affect the efficacy of anticonvulsant medications, except lamotrigine, which can have decreased efficacy when taken with estrogen.[10][45] The dose of lamotrigine may need to be adjusted, and a discussion with the prescribing clinician is recommended.[25][39] Available data is limited but suggests that gabapentin, levetiracetam, and valproate have limited effects on the metabolism of OCPs.[44] 

Age-Related Contraindications

Except for care for transgender youth, menstrual suppression should not be initiated before menarche; adolescents must first demonstrate normal anatomy and typical pubertal development.[27][29]

Technique or Treatment

Commonly used hormonal contraceptives may be leveraged to achieve menstrual suppression, including continuous or extended use of the combined OCP, the combined transdermal patch, the combined intravaginal ring, the progestin-only pill, and DMPA, as well as LARC methods such as the levonorgestrel-releasing IUD and the subdermal etonogestrel implant. Less commonly used options include GnRH agonists and testosterone. Complete cessation of menses is difficult to achieve, and success rates and associated side effects vary between methods. Therefore, although complete amenorrhea is possible for some, patients should be counseled on realistic expectations, with the typical goal being to decrease bleeding days and associated burdens.[3][5]

Combined Oral Contraceptive Pills 

Continuous or extended use of monophasic combined OCPs is the most well-known method of menstrual suppression. Suppression is achieved by taking a daily pill continuously without pausing for a placebo week to precipitate withdrawal bleeding.[3][12] In a typical pack with 21 active pills and 7 placebo pills, a patient is instructed to take the 21 active pills and then start the active pills of a new pack on day 22. A 2014 Cochrane Review confirmed that this could be done safely and with similar contraceptive efficacy to 28-day cyclic dosing for an indefinite number of cycles.[3][12] 

Numerous monophasic formulations and brands are available, though they all contain ethinyl estradiol in combination with a progestin (eg, norethindrone, levonorgestrel, norgestimate, or drospirenone). Different formulations have varying ethinyl estradiol dosages combined with various progestins, though, in monophasic formulations, the dose of hormones is the same for each pill in the pack. Triphasic formulations are not utilized for menstrual suppression because the varying hormone levels throughout the pack increase the risk of breakthrough bleeding.

Based on an older Cochran review, OCPs with higher doses of ethinyl estradiol (20 µg) have been associated with lower rates of bothersome breakthrough bleeding than low-dose OCPs (≤20 μg ethinyl estradiol). (Please refer to the Complications section for more information on bleeding disruptions). However, the studies reviewed comprised various progestin types, which also may have affected the reported incidence of irregular bleeding; therefore, the Cochran review authors suggested more research was needed before solely attributing bleeding disruptions to the estrogen dosage.[3][46] Higher rates of amenorrhea are reported as the number of cycles of continuous use increases, with approximately 50% reporting amenorrhea after 2 or 3 cycles, 69% after 6 or 7 cycles, and 79 to 88% after 12 or 13 cycles.[47][48]

OCP benefits include ease of use, wide accessibility, and abundant safety and efficacy evidence. Furthermore, clinicians are generally knowledgeable and comfortable with OCPs. OCPs are also associated with improvements in perimenstrual symptoms, including dysmenorrhea, fatigue, bloating, and headache.[12][47] Additionally, some patients may prefer OCPs to LARC methods due to perceived greater personal control over their cycles and suppression.[5] The disadvantages include the need for daily patient compliance, the inability to utilize OCPs in patients with contraindications to exogenous estrogen (Please refer to the Contraindications section for more information), and the risk of breakthrough bleeding, which is of variable annoyance for patients.[3][12] 

Combined Transdermal Patch

The transdermal combined contraceptive patch can be used continuously, similarly to OCPs, for menstrual suppression.[3] The patch is replaced weekly with no break week taken to precipitate withdrawal bleeding. Moderate rates of amenorrhea may be achieved; extended use for 12 weeks showed fewer overall bleeding days (6 versus 14) and fewer breakthrough spotting episodes (2 versus 3) compared to traditional cyclic use.[49]

The primary advantage of transdermal patches is weekly rather than daily dosing. Data on prolonged use is limited, as only the ethinyl estradiol 75 µg/norelgestromin 6 mg version of the patch has been studied.[3][49] Breakthrough bleeding is the most common adverse effect.[3][49] However, the combined transdermal patch cannot be used in patients with contraindications to exogenous estrogen. (Please refer to the Contraindications section for more information). 

Intravaginal Ring

Similar to the patch, the combined intravaginal contraceptive ring can be used continuously for menstrual suppression. The intravaginal ring is typically replaced every 4 weeks without a hormone-free interval. Only the monthly ethinyl estradiol 0.015 mg/etonogestrel 0.120 mg ring has been studied specifically for menstrual suppression.[3] This method demonstrates excellent amenorrhea rates; according to a 2008 study, up to 89% of users had no to minimal bleeding at 6 months of continuous use.[3][50] Some evidence suggests that vaginal administration may result in more stable serum estrogen and progesterone concentrations than the patch or OCPs.[4][51]

Monthly rather than weekly or daily dosing may be advantageous for compliance and convenience and increase patients' perceived control over their menses.[5] The most significant disadvantage of the ring is bothersome breakthrough bleeding, which is a common reason for discontinuation. Although full menstrual-type bleeding days decrease with extended ring use, spotting days may increase compared to cyclic use.[3][51] However, evidence suggests that if bothersome spotting occurs for >5 days, bleeding may improve with an on-demand 4-day hormone-free interval.[50] The ring can then be replaced and used continuously.[3][50]

Another disadvantage is the requirement for refrigeration of the rings if they are to be stored by the patient longer than 4 months, which may create a barrier for those who do not have access to reliable refrigeration or electricity. The newer ethinyl estradiol 17.4 mg/segesterone acetate 103 mg ring is a longer-acting effective contraceptive that can remain in place for 12 months and does not require refrigeration or repeat prescriptions. However, data is limited regarding rates of amenorrhea achieved with continuous use of this method, and more research is necessary to understand its efficacy for menstrual suppression.[3] However, the intravaginal ring cannot be used in persons with contraindications to exogenous estrogen. (Please refer to the Contraindications section for more information).

Progestin-Only Oral Pills 

POPs, including norethindrone, norethindrone acetate, and drospirenone, may be used for menstrual suppression, particularly in persons with contraindications to exogenous estrogen.[3] The use of oral medroxyprogesterone acetate, up to 20 mg daily in divided doses, has also been described. Other progestins may be available outside the US as POPs, including desogestrel and norgestrel. Norethindrone and norethindrone acetate are different compounds, and only norethindrone 0.35 mg and drospirenone 4 mg have been approved as contraceptives in the US.[52] Amenorrhea has been reported in up to 76% of users at 2 years with standard 5 mg dosages of norethindrone acetate. However, rates are as low as 10% with standard dosages of norethindrone, and data on rates with drospirenone are limited.[3][27][52]

The main advantages of POPs are the ability to be used in individuals with contraindications to exogenous estrogen, the ease of dosage and frequency adjustments, convenience, and quick initiation.[3][39] However, the disadvantages are significant, including low and inconsistent rates of amenorrhea, higher cost compared to combined OCPs, the need for strict adherence and timed daily dosing for adequate suppression and contraceptive efficacy, and irregular breakthrough bleeding.[3][29] Moreover, progestin-only pills are not typically recommended for use in adolescents.[22]

Injectable Depot Medroxyprogesterone Acetate

DMPA 150 mg intramuscularly or 104 mg/0.65 mL subcutaneously every 11 to 13 weeks is a longer-acting contraceptive option that may be leveraged for menstrual suppression.[3] Amenorrhea rates are as high as 71% at 2 years and increase with prolonged use.[3][4] Advantages include infrequent dosing, administration ease, and high amenorrhea rates.[3][4] DMPA is a commonly used menstrual suppression method among young women with developmental or physical disabilities, though it must be used with caution due to its effect on bone health. (Please refer to the Complications section for more information).[29]

Disadvantages include initial excessive prolonged uterine bleeding with the first dose as the existing endometrial lining is shed, the need for an in-person clinic visit for repeated injections ≥4 times per year, weight gain associated with high-dose progesterone, and loss of BMD. (Please refer to the Complications section for more information).[29]

Levonorgestrel-Releasing Intrauterine Device 

The levonorgestrel-releasing IUDs, available in dosages of 52 mg, 19.5 mg, or 13.5 mg, are progestin-only LARC methods that can effectively achieve menstrual suppression. The 52 mg device demonstrates the highest rates of amenorrhea, with up to 50% of users amenorrhoeic at 6 to 12 months and 60% amenorrhoeic at 5 years.[3][4][29] Since the lower dose devices have lower amenorrhea rates, the 52-mg device is preferred for the indication of menstrual suppression.[3] The devices are used for 3 to 8 years at a time, depending on device dose and brand; the 52-mg device is approved for contraception for up to 8 years, and menstrual suppression rates appear to remain high throughout that time. 

Levonorgestrel-releasing IUD benefits include excellent contraceptive efficacy (<0.2% failure rate), lower menstrual blood loss volume, long duration of the use for a single device, reliable compliance with no individual user variability), ability to utilize the device in individuals with contraindications to exogenous estrogen, and treatment benefits for some other medical conditions (eg, heavy menstrual bleeding, endometriosis, adenomyosis, leiomyomas, and hemostatic disorders).[29][39] Disadvantages include insertion-related pain and fear, the need for clinicians trained in the placement procedure, difficulty accessing the procedure, lack of clinical knowledge, up-front expense, breakthrough bleeding, and the potential for mechanical complications and expulsion.[3][29] (Please refer to the Complications section for more information). Breakthrough bleeding is most likely during the initial 3 to 6 months after placement and improves with time; as few as 11% of users will experience spotting at 2 years.[29] 

ACOG supports using levonorgestrel-releasing IUDs in adolescents for menstrual suppression.[22][53] Previous concerns that placement in nulligravid adolescents would be impossible or lead to higher rates of expulsion or uterine perforation have not been substantiated in studies. The expulsion risk is low at 8%, and the reported risk of perforation is as low as 0%.[22]

Many misunderstandings and fears regarding the IUD exist that decrease its popularity for menstrual suppression and contraception in general, including perceived lack of personal control over menses, fear of pain or complications associated with placement, fear of having a foreign object inside the body, and the absence of reassurance that conception has not occurred provided by a predictable period.[5] Appropriate counseling can help alleviate some of these concerns. However, clinicians must not dismiss patient concerns or make patients feel coerced.[3] Conversely, the copper-containing IUD is inappropriate for menstrual suppression, as it does not alter menstrual cycle physiology or the endometrial lining.[4][39]

Subdermal Etonogestrel Implant 

The subdermal etonogestrel-containing implant is an extremely effective contraceptive device (<0.05% failure rate) and an additional method to consider for menstrual suppression.[39] However, amenorrhea rates are inconsistent and reported to be as low as 13% to 22% at 12 months, and the risks of menstrual irregularity and breakthrough bleeding are high.[3][29] Subdermal implants are not typically recommended for menstrual suppression in adolescents because up to 22% of adolescent users request removal for breakthrough bleeding.[22] Furthermore, the high upfront cost and insertion-related pain should also be considered.[3]

GnRH Agonists 

GnRH agonists are noncontraceptive medications that may be utilized for menstrual suppression by creating a hypoestrogenic state.[3][29] Although counterintuitive, GnRH's continuous presence inhibits FSH and LH release, which typically respond to intermittent GnRH pulses. The most common formulation is depot-leuprolide acetate 11.25 mg, injected intramuscularly every 12 weeks. Other formulations include 3.75 mg intramuscularly monthly and subdermal implants or intranasally at varying doses.[3][29] Triptorelin may also be utilized. 

GnRH agonists are utilized in transgender and gender-diverse adolescents for delay or blockade of puberty in support of gender-affirming care, in individuals with malignancy, or in individuals with endometriosis or severe heavy menstrual bleeding with anemia which is refractory to other hormonal treatments.[3][29][22] Rates of amenorrhea are as high as 96%.[29][43] However, several significant disadvantages are associated with the hypoestrogenic state induced by GnRH agonists, including perimenopausal symptoms and a decrease in BMD.[3][22][29] (Please refer to the Contraindications section for more information). Patients should also be counseled to expect an initial "flare" in bleeding within 1 to 3 weeks until hormone levels are adequately suppressed.[43] Additionally, GnRH agonists are very expensive, ineffective as a form of contraception, and may be less accessible in the primary care setting due to lower clinician familiarity.[3] Experts recommend GnRH agonists not be used for a prolonged period due to risks of BMD loss; add-back therapy (eg, norethindrone acetate 5 mg once daily) can help reduce this risk and minimize other bothersome symptoms.[29]

Testosterone 

Among transgender and gender-diverse persons, testosterone can be used for menstrual suppression. Testosterone acts directly on the endometrium, causing atrophy.[54] Testosterone can be administered via topical gel, subcutaneous injection, or intramuscular injection. Intramuscular injection is the most common with testosterone enanthate or cypionate. A typical starting dose of both formulations is 100 mg every 2 weeks intramuscularly.[34] Amenorrhea is achieved in a dose-dependent response to testosterone, with higher or more frequent doses achieving amenorrhea sooner.[55] Across formulations, amenorrhea is typically achieved within 6 months.[29][55][56] Testosterone is not an adequate contraceptive method, and pregnancy has been reported while actively using testosterone.[36][29]

Complications

Breakthrough Bleeding

The most common adverse event of menstrual suppression in all patient populations is breakthrough bleeding at unexpected times. This bleeding is benign, though it can be distressing or inconvenient and is a common reason for treatment discontinuation.[3] Up to 46% of individuals may experience breakthrough bleeding across methods, most commonly with the subdermal etonogestrel implant and progestin-only pills.[3][29] Clinicians should counsel patients regarding possible benign breakthrough bleeding, and rates decrease with a longer duration of continuous hormonal contraceptive use, particularly if used more than 6 months.[3] 

ACOG suggests the following strategies for breakthrough bleeding management depending on the menstrual suppression method:

• For CHCs, including OCPs, patches, or rings
  • Consider cyclic cycles for 3 to 6 months, then transition to extended cycles (eg, use CHCs for 12 weeks, followed by a 4- to 7-day hormone-free interval).
  • Complete a 3- to 4-day hormone-free interval.
  • Supplement intermittently with estrogen.[3][12][50]
• For POPs
  • Counsel that breakthrough bleeding may decrease with consistent daily dose timing (eg, taking the dose simultaneously each day).
  • Increase the dosage.
  • Completing a brief dose taper of norethindrone (eg, increase to 0.7 mg for 7 days, then returning to standard 0.35 mg dose).[3] 

• For DMPA or the etonogestrel implant
  • Use combined OCPs or oral estrogen alone for 10 to 20 days.
  • Administer a course of non-steroidal anti-inflammatory drugs (NSAIDs) for up to 7 days.
  • Increase injection frequency of DMPA to rapidly achieve amenorrhea (up to every 4 to 6 weeks for 2 to 3 doses), then consider returning to regular dosing.[3][4] 
• For levonorgestrel-releasing IUD
  • Use higher device dosages (ie, 52 mg levonorgestrel).
  • Prescribe a brief course of combined OCPs or progestin-only pills, scheduled NSAIDs, or oral sub-antimicrobial-dose doxycycline.
  • Manage expectantly for up to 6 months.
  • Counsel patients on alternative methods.[3]

Complications Related to Estrogen

Complications specific to estrogen-containing methods include thromboembolism (eg, DVT, PE, stroke), new or worsening of prior hypertension, cardiac events when used in patients with cardiovascular disease, and hepatic hemangioma.[4][39] These risks are similar in special populations. Previously, concerns were raised regarding cancer risk associated with the long-term use of OCPs. However, a 2017 study of over 46,000 women demonstrated a decreased risk of colorectal, endometrial, ovarian, and hematological cancers in those with OCP use within their lifetime.[16] The study also showed that any increased risk of breast and cervical cancer seen initially in OCP users resolves within 5 years of discontinuation.

Complications Related to Progestins

Injectable medroxyprogesterone acetate is associated with decreased BMD when used for ≥2 years, though this loss is largely reversible.[4][15][22][29] Elevated levels of biomarkers for bone formation and resorption and lower average BMD have been seen in long-term users compared to non-users.[4] BMD loss increases with longer DMPA use, at least 2 years, with studies showing BMD loss at the hip and spine of 0.5% to 3.5% at 1 year and up to 7.5% at 2 years.[15] Complete recovery of BMD loss is highly likely if DMPA is used for <2 years.[3][22][29]

However, BMD loss may level out beyond that, with a significant portion of the loss reversible. A prospective cohort study of 248 new DMPA users showed a BMD loss of only 5.4% compared to their baseline after 5 years of use.[57] Results from this same study showed substantial BMD recovery within 2 years of discontinuation, with BMD only 1.2% below their original by 96 weeks posttreatment.[22] The main concern with this effect is the possibility of a higher risk of osteoporosis, bone stress injury, or fulminant fracture. Among individuals who already carry these risks for other reasons, including athletes or military personnel with high-volume weight-bearing physical activities, previous bone stress injury, athletes with low energy availability, nutritional deficiencies, middle-aged patients, chronic steroid use, or immobility, increased risk of bone loss is a concern.[37][38] No high-quality evidence demonstrates fracture risk later in life in DMPA users.[15]

Some evidence suggests that age-appropriate supplemental calcium of 1200 mg daily and vitamin D may decrease adolescent BMD loss if taken concurrently with DMPA.[22] Despite the concern for BMD loss, the benefits of preventing pregnancy or suppressing menses may outweigh this risk, even in adolescents. ACOG and AAP do not recommend limiting the duration of use to 2 years.[22] Patients should be counseled on the risks and benefits so they may make the most informed decision for themselves.[22] The etonogestrel implant and LNG-IUD are not associated with BMD loss. Additionally, progestins do not have substantiating evidence to suggest an increased risk of breast cancer, cardiovascular disease, or thromboembolism.

Complications Related to GnRH Agonists

Adverse effects specific to GnRH agonists stem from the induction of a hypoestrogenic state, including BMD loss, the risk for cardiovascular disease, headache, and menopausal symptoms such as hot flashes, mood changes, and fatigue.[3][22][29]

Impact on Fertility

One of the common fears associated with menstrual suppression and hormonal contraception, in general, is the fear of alteration in baseline fertility after use. Baseline fertility rates do not appear to be affected by any methods beyond average age-related fertility decline. However, a delay in the resumption of ovulation and regular menses may occur, depending on the method and duration of use. For this reason, within the first several months of discontinuing hormonal contraception, fertility rates in people using hormonal menstrual suppression methods may be lower than fertility rates in non-users. This initial delay is more likely seen in DMPA and CHC users than IUD users. However, no significant difference in pregnancy rates between methods by 1 year has been observed after discontinuation.[58] Additionally, after 12 months of attempting conception, the overall birth rate in patients using menstrual suppression methods appears comparable to the general population.[58]

Clinical Significance

Up to 26% of the global population menstruates.[1] Approximately 800 million people menstruate on any given day, and bothersome menstrual-related symptoms (eg, heavy menstrual bleeding, dysmenorrhea, premenstrual syndrome, bloating, fatigue) impact up to 2.5 million people annually.[1][4] Negative symptoms associated with menses may lead to absenteeism from school or work, resulting in loss of education and income, decreased participation in social, athletic, professional, or recreational activities, embarrassment or social ostracization, excessive income spent on menstrual hygiene products, including pads, tampons, menstrual cups, and panties, increased risk for genitourinary infections, and excessive blood loss and associated anemia. These consequences may disproportionately impact those living in poverty, adolescents, persons with developmental or physical disabilities, gender-diverse persons, military personnel, athletes, and persons with malignancy (Please refer to "Special Populations" in the Indications section for more information on "period poverty").

By utilizing menstrual suppression methods, amenorrhea or oligomenorrhea may be achieved, and the described negative impacts of menses may be mitigated. (Please refer to "Special Populations" in the Indications section for more information on the adverse effects of menses). The amenorrhea rates for each method are as follows:

• OCPs: 88% by 12 months
• POPs: widely variable depending on formulation and dose, 10 to 76%
• DMPA: up to 71% by 2 years
• Levonorgestrel-releasing IUD: 50% by 12 months, 60% by 2 years
• Subdermal etonogestrel implant: 13 to 22%
• GnRH agonists: up to 96%
• Testosterone: undefined [3]

Enhancing Healthcare Team Outcomes

Enhancing patient-centered care, outcomes, patient safety, and team performance related to menstrual suppression requires a multifaceted approach involving skills, strategies, responsibilities, interprofessional communication, and care coordination among healthcare professionals. Physicians, advanced practitioners, nurses, pharmacists, and other health professionals must know the indications, methods, benefits, and risks of menstrual suppression. This comprehensive understanding allows them to effectively address patient concerns and misconceptions about menstrual suppression being "unnatural" or harmful. Clinicians must provide evidence-based counseling that respects patients' beliefs and cultural backgrounds.

Interprofessional communication is crucial in various healthcare settings, from community clinics to large medical centers, where menstruating individuals may seek care. Team members, including family medicine physicians, pediatricians, gynecologists, nurse practitioners, and endocrinologists, must collaborate to offer consistent and accurate information. For adolescents, clinicians should balance the involvement of parents or caregivers with the adolescent's autonomy, being mindful of local laws regarding adolescent consent for contraceptives and sexual healthcare.

In cases involving individuals with developmental or physical disabilities, the decision-making process should involve caregivers while prioritizing the patient's preferences and values. Transgender and gender-diverse individuals require a coordinated approach from an interprofessional team that includes medical and mental health professionals specializing in gender-affirming care. Mental health professionals are vital in facilitating shared decision-making and providing continuous support. By fostering effective interprofessional communication and care coordination, healthcare teams can ensure safer, more effective, patient-centered menstrual suppression care.

Disclosures

The views expressed in this article are those of the authors and do not reflect the official policy of Evans Army Community Hospital, Womack Army Medical Center, the Department of the Army, the US Department of Defense, or the US Government.