Irregular Bleeding Pattern as adverse effect of Hormonal contraception

Irregularity in menstrual pattern is the most common clinical side-effect of hormonal contraceptives.  Therefore, an objective assessment of cycle control is critical in evaluation of a new contraceptive method for its acceptance and continuation. Bleeding   patterns   are   more   predictable   in   users   of   combined injectables.

Progestin-only   oral   contraceptives   may   cause   increased   days   of menstrual bleeding as subdermal progestin implants while combined pills may cause a decrease in days of bleeding. The use of copper IUDs is associated with increased bleeding in 18-20%  of users during the initial period of three months which   improves   with   prolonged   use while levonorgestrel-releasing   devices significantly,  decreased bleeding (1).  However,  most these disorders are not clinically   significant, they   can   lead   to   erratic   method   use   or   even   to discontinuation(2).

Early and/or late withdrawal bleeding and irregular bleeding (spotting and breakthrough bleeding) occurred more frequently in women taking COCs containing very low-dose EE(15 mcg) than in those using COCs containing 20 mcg EE(3).  Although vaginal ring(EE15 μg/etonogestrel 120 μg)  users reported significant better cycle control than oral contraceptives containing 15, 20 or 30 mcg EE (4,5,6).

In Milson study, breakthrough bleeding and spotting result less frequent with the vaginal ring than with the oral contraceptive containing EE 30mcg (4.7-10.4%)  and intended bleeding was significantly better for all cycles with NuvaRing (68.5-56.6%)  (7,8).  A preliminary study reported more high acceptability in ring than in patch users (9).  Good cycle control was,  generally reported in combined HC containing EE 30mcg (10,11,12)

However,  the comparison between an oral contraceptive containing 20 microg ethinylestradiol and 75 microg gestodene,  with a reference preparation containing 30 microg ethinylestradiol combined with 75 microg gestodene too,  demonstrated that the two regimens had no difference in cycle control, efficacy, and side-effects. The occurrence of spotting and breakthrough bleeding was low and was not different between   these   two   preparations(13).

It   was   reported   that   the   long-acting progestogen –only contraceptives like levonorgestrel(LNG)- releasing subdermal implants,  Norplant or intrauterine devices(LNG-IUD)  as well as injectable contraceptive NET-EN 200mg given 2 or 3 monthly,  produced disturbances in bleeding pattern in the majority of their users. Combined injectable contraceptives containing 50mg NET EN and 5 mg estradiol valerate caused less bleeding problems with half of the users experiencing normal pattern during one year of its use (14,15)

Combined low-dose pill,  both triphasic and monophasic, produce much better cycle control and almost 90% of users have normal bleeding patterns during one year of method use. In spite of supposed advantages of triphasic pill, randomized prospective studies on triphasic versus monophasic formulation no reported   significant   differences   in   effectiveness,  bleeding   patterns   or discontinuation rates(16).  The biphasic pill compared to triphasic pill seems to have an increase of breakthrough bleeding but the choice of progestin may be more important that the phasic regimen in determining bleeding patterns (17).

Yet,  considering biphasic pill versus monophasic pill, extensive evidence is available for monophasic pill. Therfore,  it is advisable to prefer the monophasic formulation (18). Progestogen-only(3-ketodesogestrel)  contraceptive   implant (Implanon) induce variable bleeding pattern and is characterized by relatively few bleeding events resulting acceptable to most subjects (19). When long-acting implants, injectables   or   hormonally   impregnated   intrauterine   systems   are prescribed, women should be informed of irregular bleeding and following amenorrhoea prior to starting the method choosed(20).

A study has evaluated the effectiveness on cycle control of two formulations low-dose EE combined with drospirenone 3mg or desogestrel 150 mcg and showed that it is comparable between both groups as frequency of withdrawal bleeding without negative effects on tolerability(21)

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