Mild Adverse effects of Hormonal contraception

Adverse effects represent the main factors in determining acceptability and compliance with any contraceptive method. Most frequent symptoms are: weight gain, nausea, breast tenderness and menstrual disorders(1). Mild and transitory disturbances are common in the first cycles of hormonal contraception and usually disappear after this period without any problem.  Women often stop hormonal contraception because of perceived weight changes(2).  This suggestion affects particularly, adolescents   and   young   women   preoccuped   with   body   image.

However, it is important to remember that breast tenderness, headache, nausea and oedema also occur in the general population and during use of placebo(3,4). Is there a real evidence of weight gain? Several studies are carried out with the aim to clarify if weight increase with hormonal contraceptives is real or only a common misperception.

The combination ethinylestradiolEE)  20mcg/ levonorgestrel(LNG) 100mcg seems to have no significant impact on body weight and body composition(fat mass, fat-free mass, total body water, intracellular water, extracellular water)(5).  A multicenter comparative study between norgestimate (NGM)  180/215/250 mcg/EE 25mcg versus norethindrone acetate 1mg/EE 20 mcg showed that only the 0.3%  of users, in both groups, experienced a 10% increase in weight (6).

A recent randomized, prospective study evaluating the incidence of side-effects in women using EE 20 mcg/LNG 100 mcg or EE 15 mcg/  gestodene 60 mcg or vaginal ring (EE 15mcg/etonogestrel-ENG 120mcg) reported no significant weight gain into three groups. Particularly, over 1 year of treatment, the maximum weight gain from baseline was 2,8 kg in the first group 1,6 kg in the second group and 0,8 in the thirt group(7)

Another study which compared the formulations EE 30mcg/chlormadinone acetate 2mg and EE 30 mcg/Drospirenone 3 mg showed no significant increase in body weight in both groups of adolescents considered as demonstrated in other trials (8,9,10,11). Injectable contraceptive methods are safe, reliable and worldwide used.  Depot-medroxyprogesterone acetate(DMPA)  is the most commonly used injectable in the United States;  but during its use irregular bleeding, breast tension, weight gain and impact on bone mineral density should be taken into account(12).

However, no differences in mean bone mineral density of distal forearm between DMPA and IUD users were showed;  even though DMPA induces estrogen deficiency as demonstrated with measures performed 5 days after cessation of menstruation(13). So,  the relationship between DMPA and changes in bone density remains controversial despite a substantial number of studies evaluating this potential association(14).

On the other hand,  weight gain and decreased bone density were frequently documented in adolescents on DMPA, particularly with longer duration of use(15). In the mean time, the higher rate of adolescent’s unintended pregnancy in the industrialized countries induces to accept this potential bone risk considering the absolute priority to reduce the pregnancy risk in this age group.

In women with a tendency to weight gain, under oral contraceptives because of water retention, the use of EE 20-30 mcg/drospirenone(DRSP)  3 mg seems the ideal method to avoid this problem(9,16) .The use of a LNG-IUS(intrauterine system)  during five years caused no significant weight increase and the difference in weight was of the same magnitude as that of copper IUD(intrauterine device)  use.(17).  In addition,  a cohort study of lower and middle class Brazilian copper IUD users during ten years, explains that these women tend to gain weight during their reproductive life, because   of   other   factors(18).

So, although   weight   gain   is   perceived   as   a disadvantage of oral contraception, no real weight increase was reported in the majority of current investigations. It is found no decrease in the reporting of symptoms with the reduction of estrogen dose,nor with use of third-generation progestins.  Little variation between monophasic and triphasic formulations was reported(1).  Nevertheless,  the fear of weight gain with oral contraceptives can lead to noncompliance and method discontinuation. Woman need reassurance to remove   such   misperceptions.  In   fact,  lack   of   informative   communications between gynaecologist and user and mistaken knowledge may contribute to ignorance about HC and misperceptions, particularly in adolescents (18,19)

Rosa Sabatini and Raffele Cagiano
Department of Obstetrics and Gynecology
Department of Pharmacology General Hospital Policlinico-University of Bari, Italy


  1.   Moreau,  C.,  Trussell,  J.,  Gilbert,  F.,  Bajos,  N.,  Bouyer,  J.  (2007). Oral contraceptive tolerance:does the type of pill matter? Obstet. Gynecol,109(6), 1277-85
  2. O’Connell, K.J., Osborne, L.M., Westhoff, C. (2005). Measured and reported weight change for women using a vaginal contraceptive ring vs. a low-dose oral contraceptive.Contraception, 72(5), 323-7.
  3. Redmond, G., Godwin, A.J., Olson, al. (1999). Use of placebo controls in an oral contraceptive trial: methodological issues and adverse events incidence. Contraception, 60,81-85. 
  4. Coney,  P., Washenik,  K.,  Langley,  R.G.,  DiGiovanna,  J.J.,  Harrison,  D.D. (2001).  Weight change and adverse event incidence with a low-dose oral contraceptive: two   randomized, placebo-controlled   trials.  Contraception, 63(6), 297-302.
  5. Lello, S., Vittori, G., Paoletti, A.M., Sorge, R., Guardianelli, F., Melis, G.B. (2007).  Effects on body weight and body composition of a low-dose oral estroprogestin containing ethinylestradiol 20 microg plus levonorgestrel 100 microg.Gynecol. Endocrinol, 23(11), 632-7.
  6. Burkman, R.T., Fisher, A.C., LaGuardia, K.D. (2007). Effects of low-dose oral contraceptives on body weight: results of a randomized study of up to 13 cycles of use. J. Reprod. Med, 52(11),1030-4. 
  7. Sabatini, R., Caggiano, R. (2006). Comparison profiles of cycle control, side effects   and   sexual   satisfaction   of   three   hormonal   contraceptives. Contraception, 74(3), 220-3. 
  8. Sabatini,  R., Orsini,  G., Cagiano,  R.,  Loverro,  G.  (2007).  Noncontraceptive benefits of two combined oral contraceptives with antiandrogenic properties among adolescents. Contraception,76, 342-347. 
  9. Foldart, J.M. (2000). The contraceptive profile of a new oral contraceptive with antimineralocorticoid and antiandrogenic effects. Eur.J. Contracept. Reprod. Health Care, Suppl.3,25-33.
  10.   Suthipongse,  W., Taneepanichskul,  S.  (2004).  An open-label randomized comparative study of oral contraceptives between medications containing 3 mg drospirenone/30 microg ethinylestradiol and 150 microg levonogestrel/30 microg ethinylestradiol in Thai women.  Contraception, 69(1), 23-6.
  11.   Schramm,  G.,  Steffens,  D.  (2003).  A 12-month evaluation of the CMA-containing   oral   contraceptive   Belara:  efficacy, tolerability   and   anti-androgenic properties.Contraception, 67(4), 305-12. 
  12.   Haider,  S.,  Darney,  P.D.  (2007).  Injectable contraception. Clin.Obstet.Gynecol, 50(4), 898-906.
  13.   Taneepanichskul S., Intaraprasert S., Theppisai U., Chaturachinda K.(1997).  Bone mineral density in long-term depot medroxyprogesterone acetate acceptors. Contraception, 56(1), 1-3.
  14.   Westhoff,  C.  (2002).  Bone mineral density and DMPA.  J.Reprod.Med, 47(9), 795-9. 
  15.   Bonny,  A.E.,  Harkness,  L.S.,Cromer,  B.A.  (2005).  Depot medroxyprogesterone   acetate: implications   for   weight   status   and   bone mineral density in the adolescent female. Adolesc. Med.Clin, 16(3), 569-84. 
  16.   Borges,  L.E.,  Andrade,  R.P.,  Aldrighi,  J.M.,  Guazzelli,  C.,Yazlle,  M.E., Isaia, C.F., Petracco, A., Peixoto, F.C., Camargos, A.F. (2006). Effects of a combination of ethinylestradiol 30 microg and drospirenone 3 mg on tolerance,cycle control,general well-being and fluid-related symptoms in women with premenstrual disorders requesting contraception. Contraception, 74(6), 446-50. 
  17.   Yela,  S.A.,  Monteiro,  I.M.,  Bahamondes,  L.G.,  Del   Castillo,  S., Bahamondes, M.V., Fernandes, A. (2006). Weight variation in users of the levonorgestrel-releasing intrauterine system,  of the copper IUD and of medroxyprogesterone acetate in Brazil.  Rev.Assoc.  Med.  Bras,52(1),  32-6. 1.
  18.   Hassan,  D.F.,  Petta,  C.A.,  Aldrighi,  J.M.,  Bahamondes,  L.,  Perrotti,  M. (2003). Weight variation in a cohort of women using copper IUD for contraception.Contraception, 68(1), 27-30.
  19.   Hamani,  Y.,  Scaki –Tamir,  Y.,  Deri-Hasid,  R.,  Miller –Pogrund,  T., Milwidsky,  A.,  Haimov-Kochman,  R.  (2007).  Misperception about oral contraception   pills   among   adolescents   and   physicians.Hum.Reprod, 22(12),3078-83.

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