Medroxyprogesterone dosing

Progestin-only contraceptives (Fig. 4) contain low-doses of progestins (e.g. 350 pg norethindrone or 75 pg norgestrel) that have to be administered daily without interruption. The lowest expected failure rate during the first year of use is 0.5%, while the typical failure rate amounts to 3%. Subdermal implants of norgestrel (216 mg) for sustained release provides for long-term (for up to 5 years) contraceptive effects characterized by failure rates of only 0.05%. Reliable contraception for 3 months can be achieved by an intramuscular injection of a crystalline suspension of 150 mg medroxyprogesterone acetate (Fig. 3) (failure rate 0.3%). 

Table 46-1 illustrates the pathophysiology of amenorrhea relative to the organ system(s) involved, as well as the specific condition that results in amenorrhea. Amenorrhea is also a normal side effect that may result from the use of low-dose oral contraceptives (OCs), extended-cycle OC pill use, or depot medroxyprogesterone acetate use.5 Many women may experience delayed return of menses after discontinuation of OCs. Postpill amenorrhea usually is a self-limited condition. Further evaluation for other unrecognized conditions, such as polycystic ovary syndrome (PCOS), should be considered if spontaneous resolution of the amenorrhea does not occur within 3 to 6 months following discontinuation of the OCs.6,7... 

Utian WH, Shoupe D, Backmann G, et al. Relief of vasomotor symptoms and vaginal atrophy with lower doses of conjugated equine estrogens and medroxyprogesterone acetate. Fertil Steril 2001 75 1065-1079. 

Drug-induced osteoporosis may result from systemic corticosteroids (prednisone doses greater than 7.5 mg/day), thyroid hormone replacement, some antiepileptic drugs (e.g., phenytoin, phenobarbital), depot medroxyprogesterone acetate, and other agents. 

Low-dose hormone therapy (conjugated equine estrogen 0.45 mg and medroxyprogesterone acetate 1.5 mg/day) has demonstrated equivalent symptom relief and bone density preservation without an increase in endometrial hyperplasia. Whether such lower doses will be safer (cause less venous thromboembolism and breast cancer) remains to be seen. 

Fertility impairment Medroxyprogesterone acetate at high doses is an antifertility drug. High doses would be expected to impair fertility until the cessation of treatment. 

Pharmacology Medroxyprogesterone, when administered IM at the recommended dose to women every 3 months, inhibits the secretion of gonadotropins which, in turn, prevents follicular maturation and ovulation and results in endometrial thinning. These actions produce its contraceptive effect. 

Pharmacokinetics Following a single 150 mg IM dose, medroxyprogesterone concentrations increase for approximately 3 weeks to reach peak plasma concentrations of 1 to 7 ng/mL. The levels then decrease exponentially until they become undetectable (less than 100 pg/mL) between 120 to 200 days following injection. The apparent half-life following IM administration is approximately 50 days. 

A low dosage of progestin ( mini-pill ) is used, in the form of medroxyprogesterone acetate, which is active at a very low dose. The mini-pill does not inhibit ovulation, but rather interferes with the endometrium and the cervical mucus. The use of this pill prevents most of the side effects of oral contraception, specifically nausea, water retention, and in some cases thrombophlebitis. However, a lower success rate and other frequent side effects have reduced the widespread acceptance of this preparation. Nevertheless, the mini-pill has a role to play in certain specific situations. For example, in an uncommon form of epilepsy called catamenial epilepsy, female patients will experience seizures at particular times during their menstrual cycle, reflecting the fact that seizure focus is stimulated by estrogens but inhibited by progestins. In such women, the mini-pill may afford not only birth control but also improved seizure control. 

Medroxyprogesterone acetate, 10-20 mg orally twice weekly—or intramuscularly in doses of 100 mg/m2 every 1-2 weeks—will prevent menstruation, but it will not arrest accelerated bone maturation in children with precocious puberty. 

Preparations of progesterone and medroxyprogesterone have been used to treat premenstrual syndrome. Controlled studies have not confirmed the effectiveness of such therapy except when doses sufficient to suppress ovulation have been used. 

Only one implantable contraceptive preparation is available at present in the USA. Etonogestrel, also used in some oral contraceptives, is available in the subcutaneous implant form listed in Table 40-3. Several hormonal contraceptives are available as vaginal rings or intrauterine devices. Intramuscular injection of large doses of medroxyprogesterone also provides contraception of long duration. 

It has long been considered that the risk of endometrial carcinoma may be somewhat reduced by HRT, but that the risk is affected by the dose of progestogen used, if any. In a recent population-based case-control study covering 647 cases and 1209 controls, users of estrogen + medroxyprogesterone acetate (MPA) given for 10-24 days monthly in a dose of 100 mg/month or more showed the same risk of endometrial cancer as women not using HRT... 

The impact of a new formulation of low-dose micronized medroxyprogesterone plus 17-beta-estradiol on lipid profiles in menopausal women has been studied for 12 months. Total cholesterol concentrations fell 8.4%, low-density lipoprotein cholesterol fell 18%, and high-density lipoprotein cholesterol increased 6.9% total triglycerides increased 12%. The most frequently reported adverse events were menorrhagia, breast tenderness, cervical polyps or cysts, bloating, fatigue or lethargy, influenza or a flu-like syndrome, back pain, headaches, irritability, and depression (34). 

Harrison RF, Magill P, Kilminster SG. Impact of a new formulation of low-dose micronised medroxyprogesterone and 17-beta estradiol, on lipid profiles in menopausal women, din Drug Invest 1998 16 93-9. 

Medroxyprogesterone acetate is given in a relatively high dose for hormonal contraception and acts primarily by inhibiting ovulation. However, as with the other progestogen-only contraceptives, other mechanisms probably play a very significant role. It is extremely effective, with less than one pregnancy per 100 woman-years. 

In addition to its use as a contraceptive, medroxyprogesterone acetate has also been used to treat benign prostatic hyperplasia, in which intermediate doses (for example 150 mg) are used (5), and to stimulate the appetite in patients receiving palliative care for cancer, although little published work can be found to support the latter indication. 

The contraceptive efficacy of depot medroxyprogesterone acetate does not appear to be affected by interactions with other drugs some interactions are known (6), but the doses used for contraceptive purposes are sufficient to remain effective even if metabolism is increased, for example by aminoglutethimide or phenytoin. 

Treatment with low-dose medroxyprogesterone acetate (50 and 150 mg/day) for endometriosis reduces HDL cholesterol (15) confined to the HDL2 subfraction, which was lowered by as much as 58% after 24 weeks of treatment the effect was clearly dose-related in the therapeutic dosage range. 

There is a disputed effect on carbohydrate metabolism, but it is at most mild and there is certainly no precipitation of diabetes in healthy women. Carbohydrate metabolism was unaffected by medroxyprogesterone in one study in which there was modest impairment of glucose tolerance among users of levonorgestrel-containing, low-dose combined oral contraceptives and progestogen-only tablets (18). 

Metabolic effects seen when the drug is used in high doses for other purposes (notably the treatment of breast and endometrial cancer) are unlikely to be seen in contraceptive use. This applies to the glucocorticoid potency that medroxyprogesterone undoubtedly possesses to some degree at the higher doses adrenal suppression can be observed (20) but not at contraceptive doses (21). 

---