The Progestin Revolution: progestins are arising as the dominant players in the tight interlink between contraceptives and bleeding control

Abstract

Since the introduction of the first modern contraceptive methods, the interlink between bleeding control and contraceptive development has been a dominant and critical factor. This interplay has led to the development of safer and better contraceptive methods that are often used to control bleeding in both women with normal bleeding patterns as well as in those suffering from heavy menstrual bleeding (HMB). The success of progestin-only methods, such as hormonal IUDs or progestin dominant oral contraceptives in substantially decreasing and controlling menstrual bleeding, has led to development of multiple progestin-only protocols for the sole purpose of bleeding control. These include protocols designed to stop acute heavy bleeding as well as manage long-term bleeding. Recent publications describe a variety of protocols using high dose oral progestin pills with or without a medroxyprogesterone acetate (MPA) injection that demonstrate high effectiveness and good tolerability. Comparted to many other progestins, MPA is not converted in part into ethinyl estradiol and appears to have a progestin-only advantage. Norethindrone acetate (NET acetate) is converted in part to ethinyl estradiol and therefore is an especially good option for bleeding control in patients with low estrogen levels that would benefit from estrogen replacement (such as in premenopausal women with premature menopause or hypothalamic hypogonadism).

Reversible interventions for menstrual management in adolescents and young adults with gender incongruence

“…47 Unlike NETA, it has no peripheral conversion to EE, so in patients who have serious thrombotic risk or contraindication to estrogen, this may be the safer option with similar bleeding profile. 40 Ovulation is not reliably suppressed at doses less than 10 mg per day. 39 If contraception or non-daily intervention for menstrual management is desired, subcutaneous or intramuscular preparations of DMPA may be used.…”

“…These are both very effective contraceptives and effective menstrual suppressants. 6,7,23,24,37,39,40,44,53 Both the subcutaneous and intramuscular preparations of DMPA carry a black-box warning from the FDA regarding a deleterious effect on bone health with the use of either of these medications for longer than 2 years, although the risk of fracture with prolonged use of DMPA is less clear. 56 If patients desire specific contraception, DMPA in either form is an excellent choice although the provider should counsel on the risks of changes to bone health, weight gain, and delay in return to fertility.…”

“…The most diverse class of medications that can be used for menstrual suppression is synthetic progestins 3,7,24,30,35–40 These medications are available for a wide variety of indications, can be contraceptive if that is a patient’s goal, and have many different methods of delivery. This diversity of use and preparation as well as a generally favorable safety profile makes progestins as a drug class very appealing for menstrual manipulation in adolescents who have a need for it for a broad number of reasons, including disability, 6 bleeding disorder, 41 catamenial disorders including epilepsy, 42,43 or who simply prefer to avoid menstruation, 7,44 regardless of gender.…”

“…There is some peripheral conversion of NETA to EE, 40 which can limit its use in patients who have a medical contraindication to estrogen, such as a history of stroke or blood clot. This is relatively rare in the pediatric and adolescent population, although to that end if there is a true contraindication to estrogen, the author suggests considering oral medroxyprogesterone acetate (MPA), as discussed below.…”

Progestins of today and tomorrow

“…In the setting of acute heavy menses, medroxyprogesterone acetate (MPA) is a first-line therapy [25]. NETA may have more utility for heavy menses in patients with estrogen depletion (i.e., premature menopause and hypothalamic hypogonadism) as it is partially converted to ethinyl estradiol [26]. Specifically, 1-mg NETA is converted to 6-mg ethinyl estradiol [27].…”