A combined oral contraceptive pill containing 20 μg of ethinyl estradiol and 3 mg of the progestin drospirenone in a novel dose regimen (24 active pills followed by 4 placebo pills), has demonstrated efficacy for the symptoms of premenstrual dysphoric disorder, a severe form of premenstrual syndrome, with an emphasis on the affective symptoms. Drospirenone has progestagenic, anti-androgenic and anti-aldosterone properties, which differ from earlier generations of progestins, and reducing the hormone pill-free interval allows for better suppression of ovarian steroid production.
Papers of special note have been highlighted as either of interest (•) or of considerable interest (••) to readers.
2.
FuttermanLAJonesJEMiccio-FonsecaLCQuigleyME: Severity of premenstrual symptoms in relation to medical/psychiatric problems and life experiences. Percept. Mot. Skills74(3 Pt 1), 787–799 (1992).
3.
KesselB: Premenstrual syndrome. Advances in diagnosis and treatment. Obstet. Gynecol. Clin. North Am.27(3), 625–639 (2000).
4.
SternfeldBSwindleRChawlaA: Severity of premenstrual symptoms in a health maintenance organization population. Obstet. Gynecol.99(6), 1014–1024 (2002).
5.
SteinerMMacdougallMBrownE: The premenstrual symptoms screening tool (PSST) for clinicians. Arch. Women Ment. Health6(3), 203–209 (2003).
6.
ErikssonEEndicotJAnderschB: New perspectives on the treatment of premenstrual syndrome and premenstrual dysphoric disorder. Arch. Women Ment. Health4, 111–119 (2002).
7.
LandenMErikssonE: How does premenstrual dysphoric disorder relate to depression and anxiety disorders?Depress Anxiety17(3), 122–129 (2003).
8.
GinsburgKADinsayR: Premenstrual syndrome. In: Practical Strategies in Obstetrics and Gynecology.RansomSB (Ed.), W.B. Saunders Company, Philadelphia, PA, USA, 694–694 (2000).
9.
Premenstrual dysphoric disorder. I n: Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision.American Psychiatric Association. American Psychiatric Association, Washington, DC, USA, 771–774 (2000).
10.
ACOG Practice Bulletin: Premenstrual syndrome. Obstet. Gynecol.95(4) (2000).
11.
HalbreichUBackstromTErikssonE: Clinical diagnostic criteria for premenstrual syndrome and guidelines for their quantification for research studies. Gynecol. Endocrinol.23(3), 123–130 (2007).
12.
SteinerMPearlsteinT: Premenstrual dysphoria and the serotonin system: pathophysiology and treatment. J. Clin. Psychiatry61(12), 17–21 (2000).
13.
BackstromTAnderssonAAndreeL: Pathogenesis in menstrual cycle-linked CNS disorders. Ann. NY Acad. Sci.1007, 42–53 (2003).
14.
Stoffel-WagnerB: Neurosteroid biosynthesis in the human brain and its clinical implications. Ann NY Acad. Sci.1007, 64–78 (2003).
15.
SchmidtPJNiemanLKDanaceauMA: Differential behavioral effects of gonadal steroids in women with and in those without premenstrual syndrome. N. Engl. J. Med.338(4), 256–257 (1998).
16.
PearlsteinTBBachmannGAZacurHAYonkersKA: Treatment of premenstrual dysphoric disorder with a new drospirenone-containing oral contraceptive formulation. Contraception72(6), 414–421 (2005).
17.
This multicenter, double-blind, placebo-controlled crossover study evaluated the efficacy of drospirenone 3 mg/ethinyl estradiol 20 μg in treating symptoms of premenstrual dysphoric disorder (PMDD) and yielded outcomes with statistically significant benefit.
18.
YonkersKABrownCPearlsteinTBFoeghMSampson-LandersCRapkinA: Efficacy of a new low-dose oral contraceptive with drospirenone in premenstrual dysphoric disorder. Obstet. Gynecol.106(3), 492–501 (2005).
19.
This pivotal multicenter, double-blind, randomized clinical trial including 450 women with PMDD randomized to drospirenone 3 mg/ethinyl estradiol 20 μg in a 24/4 regimen or placebo for three treatment cycles after two run-in cycles demonstrated a significant improvement in symptoms of PMDD.
FreemanEWRickelsKYonkersKAKunzNRMcPhersonMUptonGV: Venlafaxine in the treatment of premenstrual dysphoric disorder. Obstet. Gynecol.98(5 Pt 1), 737–744 (2001).
24.
CohenLSMinerCBrownEW: Premenstrual daily fluoxetine for premenstrual dysphoric disorder: a placebo-controlled, clinical trial using computerized diaries. Obstet. Gynecol.100(3), 435–444 (2002).
25.
MinerCBrownEMcCrayS: Weekly luteal phase dosing with enteric-coated fluoxetine 90mg in premenstrual dysphoric disorder: a randomized, double-blind placebo-controlled clinical trial. Clin. Ther.24(3), 417–433 (2002).
26.
HalbreichUBergeronRYonkersKA: Efficacy of intermittent, luteal phase sertraline treatment of premenstrual dysphoric disorder. Obstet Gynecol.100(6), 1219–1229 (2002).
27.
CohenLSSoaresCNYonkersKA: Paroxetine controlled release for premenstrual dysphoric disorder: a double blind, placebo-controlled trial. Psychosom. Med.66(5), 707–713 (2004).
28.
YonkersKAHalbreichUFreemanE: Symptomatic improvement of premenstrual dysphoric disorder with sertraline treatment. A randomized controlled trial. Sertraline Premenstrual Dysphoric Collaborative Study Group. JAMA278(12), 983–988 (1997).
FergusonJM: SSRI antidepressant medications: adverse effects and tolerability. Primary Care Companion. J. Clin. Psychiatry3(1), 22–27 (2001).
31.
HirschfeldRM: Long-term side effects of SSRIs: sexual dysfunction and weight gain. J. Clin. Psychiatry64(18), 20–24 (2003).
32.
Sundstrom-PoromaaIBixoMBjornINordhO: Compliance to antidepressant drug therapy for treatment of premenstrual syndrome. J. Psychosom. Obstet. Gynaecol.21(4), 205–211 (2000).
33.
O'BrienPMCravenDSelbyCSymondsE: Treatment of premenstrual syndrome by spironolactone. Br. J. Obstet. Gynaecol.86, 142–147 (1979).
34.
WangMHammarbackSLindheBABackstromT: Treatment of premenstrual syndrome by spironolactone: a double-blind, placebo-controlled study. Acta Obstet. Gynecol. Scand.74(10), 803–808 (1995).
35.
FreemanEWRickelsKSondheimerSJPolanskyM: A double-blind trial of oral progesterone, alprazolam, and placebo in treatment of severe premenstrual syndrome. JAMA.274(1), 51–57 (1995).
36.
SchmidtPJGroverGNRubinowDR: Alprazolam in the treatment of premenstrual syndrome. A double-blind, placebo-controlled trial. Arch. Gen. Psychiatry50(6), 467–73 (1993).
37.
HarrisonWMEndicottJNeeJ: Treatment of premenstrual dysphoria with alprazolam. A controlled study. Arch. Gen. Psychiatry47(3), 270–275 (1990).
38.
MezrowGShoupeDSpicerDLoboRLeungBPikeM: Depot leuprolide acetate with estrogen and progestin add-back for long-term treatment of premenstrual syndrome. Fertil. Steril.62(5), 932–937 (1994).
39.
LeatherATStuddJWWatsonNRHollandEE: The treatment of severe premenstrual syndrome with goserelin with and without ‘add-back’ estrogen therapy: a placebo-controlled study. Gynecol. Endocrinol.13(1), 48–55 (1999).
40.
FreemanEWSondheimerSJRickelsK: Gonadotropin-releasing hormone agonist in the treatment of premenstrual symptoms with and without ongoing dysphoria: a controlled study. Psychopharmacol. Bull.33(2), 303–309 (1997).
41.
BownCSLingFWAndersenRNFarmerRGArheartKL: Efficacy of depot leuprolide in premenstrual syndrome: effect of symptom severity and type in a controlled trial. Obstet. Gynecol.84(5), 779–786 (1994).
42.
CronjeWHVashishtAStuddJW: Hysterectomy and bilateral oophorectomy for severe premenstrual syndrome. Hum. Reprod.19(9), 2152–2155 (2004).
43.
CasperRFHearnMT: The effect of hysterectomy and bilateral oophorectomy in women with severe premenstrual syndrome. Am. J. Obstet. Gynecol.162(1), 105–109 (1990).
44.
SundstromINybergSBixoM: Treatment of premenstrual syndrome with gonadotropin-releasing hormone agonist in a low dose regimen. Acta Obstet. Gynecol. Scand.78(10), 891–899 (1999).
45.
MitwallyMFGotliebLCasperRF: Prevention of bone loss and hypoestrogenic symptoms by estrogen and interrupted progestogen add-back in long-term GnRH-agonist down-regulated patients with endometriosis and premenstrual syndrome. Menopause9(4), 236–241 (2002).
46.
JoffeHCohenLSHarlowBL: Impact of oral contraceptive pill use on premenstrual mood: predictors of improvement and deterioration. Am. J. Obstet. Gynecol.189(6), 1523–1530 (2003).
47.
AndreenLBixoMNybergSSundstrom-PoromaaIBackstromT: Progesterone effects during sequential hormone replacement therapy. Eur. J. Endocrinol.148(5), 571–577 (2003).
48.
ApterDBorsosABaumgartnerW: Effect of an oral contraceptive containing drospirenone and ethinylestradiol on general well-being and fluid-related symptoms. Eur. J. Contracept. Reprod. Health Care8(1), 37–51 (2003).
49.
BrownCLingFWanJ: A new monophasic oral contraceptive containing drospirenone. Effect on premenstrual symptoms. J. Reprod. Med.47(1), 14–22 (2002).
50.
FreemanEWKrollRRapkinA: Evaluation of a unique oral contraceptive in the treatment of premenstrual dysphoric disorder. J. Womens Health Gend. Based Med.10(6), 561–569 (2001).
51.
KrollRRapkinAJ: Treatment of premenstrual disorders. J. Reprod. Med.51(4), 359–370 (2006).
52.
Yaz (drospirenone and ethinyl estradiol) [prescribing information]. Berlex, Inc., Montville, NJ, USA, October (2006).
53.
Liewellyn-JonesD: Fundamentals of Obstetrics and Gynaecology (5th Edition. Vol. 2). Faber and Faber Ltd, London, UK (1990).
54.
HatcherRAGuillebaudJ: The pill: combined oral contraceptives. In: Contraceptive Technology (17th Edition). HatcherRATrussellJStewartF (Eds). Ardent Medicine, New York, NY, USA, 405–466 (1998).
55.
Loose-MitchellDSStancelGM: Estrogens and progestins. In: The Pharmacological Basis of Therapeutics (10th Edition). HardmanJGLimbirdLEGilmanGoodman A (Eds), McGraw-Hill, New York, NY, USA (2001).
56.
FuhrmannUKrattenmacherRSlaterEP: The novel progestin drospirenone and its natural counterpart progesterone: biochemical profile and antiandrogenic potential. Contraception.54(4), 243–251 (1996).
57.
Sitruk-WareR: Pharmacology of different progestogens: the special case of drospirenone. Climacteric8(3), 4–12 (2005).
58.
MuhnPFuhrmannUFritzemeierKH: Drospirenone: a novel progestogen with antimineralocorticoid and antiandrogenic activity. Ann. NY Acad. Sci.761, 311–335 (1995).
59.
Pioneering article that characterized drospirenone pharmacologically, based on animal model data, compared it with progesterone and other progestins and concluded that it is most similar to progesterone.
60.
KeamSJWagstaffAJ: Ethinylestradiol/drospireneone: a review of its use as an oral contraceptive. Treat. Endocrinol.2(1), 49–70 (2003).
SulakPJKuehlTJOrtizM: Acceptance of altering the standard 21-day/ 7-day oral contraceptive regimen to delay menses and reduce hormone withdrawal symptoms. Am. J. Obstet. Gynecol.186(6), 1142–1149 (2002).
64.
Yasmin (drospirenone and ethinyl estradiol) [prescribing information]. Berlex, Inc., Montville, NJ, USA, October (2005).
65.
KrattenmacherR: Drospirenone: pharmacology and pharmacokinetics of a unique progestogen. Contraception62(1), 29–38 (2000).
66.
KuhnzWBlodeHZimmermannH: Pharmacokinetics of exogenous natural and synthetic estrogens and antiestrogens. In: Handbook of Experimental Pharmacology. OettelMSchillingerE (Eds), Springer-Verlag, Berlin, Germany, 261–320 (1999).
67.
OelkersW: Drospirenone – a new progestogen with antimineralocorticoid activity, resembling natural progesterone. Eur. J. Contracept. Reprod. Health Care5(3), 17–24 (2000).
68.
MuhnPKrattenmacherRBeierSElgerWSchillingerE: Drospirenone: a novel progestogen with antimineralcorticoid and antiandrogenic activity. Pharmacological characterization in animal models. Contraception51(2), 99–110 (1995).
69.
BlodeHWuttkeWLoockWRollGHeitheckerR: A 1-year pharmacokinetic investigation of a novel oral contraceptive containing drospirenone in healthy female volunteers. Eur. J. Contracept. Reprod. Health Care.5(4), 256–264 (2000).
70.
OelkersWHelmerhorstFMWuttkeWHeitheckerR: Effect of an oral contraceptive containing drospirenone on the renin–angiotensin–aldosterone system in healthy female volunteers. Gynecol Endocrinol14(3), 204–213 (2000).
71.
LudickeFJohannissonEHelmerhorstFMCampanaAFoidartJHeitheckerR: Effect of a combined oral contraceptive containing 3 mg of drospirenone and 30 microg of ethinyl estradiol on the human endometrium. Fertil. Steril.76(1), 102–107 (2001).
72.
BachmannGSulakPJSampson-LandersCBendaNMarrJ: Efficacy and safety of a low-dose 24-day combined oral contraceptive containing 20 micrograms ethinylestradiol and 3 mg drospirenone. Contraception70(3), 191–198 (2004).
73.
Open-label, multicenter, noncomparative study that determined the efficacy, safety and bleeding profile of the COC drospirenone 3 mg/ethinyl estradiol 20 μg in a 24/4 regimen.
74.
ParseyKSPongA: An open-label, multicenter study to evaluate Yasmin, a low-dose combination oral contraceptive containing drospirenone, a new progestogen. Contraception61(2), 105–111 (2000).
75.
FoidartJMWuttkeWBouwGMGerlingerCHeitheckerR: A comparative investigation of contraceptive reliability, cycle control and tolerance of two monophasic oral contraceptives containing either drospirenone or desogestrel. Eur. J. Contracept. Reprod. Health Care5(2), 124–134 (2000).
76.
OelkersWFoidartJMDomroviczN: Effects of a new oral contraceptive containing an antimineralocorticoid progestogen, drospirenone, on the rennin–aldosterone system, body weight, blood pressure, glucose tolerance, and lipid metabolism. J. Clin. Endocrinol. Metab.80(6), 1816–1821 (1995).
77.
GuidoMRomualdiDGiulianiM: Drospirenone for the treatment of hirsute women with polycystic ovary syndrome: a clinical, endocrinological, metabolic pilot study. J. Clin. Endocrinol. Metab.89(6), 2817–2823 (2004).
78.
RosenbaumPSchmidtWHelmerhorstM: Inhibition of ovulation by a novel progestogen (drospirenone) alone or in combination with ethinylestradiol. Eur. J. Contracept. Reprod. Health Care.5(1), 16–24 (2000).
79.
SangthawanMTaneepanichskulS: A comparative study of monophasic oral contraceptives containing either drospirenone 3 mg or levonorgestrel 150 microg on premenstrual symptoms. Contraception71(1), 1–7 (2005).
80.
SillemMSchneidereitRHeitheckerRMueckAO: Use of an oral contraceptive contatining drospirenone in an extended regimen. Eur. J. Contracept. Reprod. Health Care8, 162–169 (2003).
81.
MortolaJFGirtonLBeckLYenSS: Dianosis of premenstrual syndrome by a simple, prospective, and reliable instrument: the calendar of premenstrual experiences. Obstet. Gynecol.76(2), 302–307 (1990).
82.
EndicottJNeeJHarrisonW: Daily Record of Severity of Problems (DRSP) reliability and validity. Arch. Womens Ment. Health9(1), 41–49 (2005).
83.
EndicottJNeeJHarrisonWBlumenthalR: Quality of Life Enjoyment and Satisfaction Questionnaire: a new measure. Psychopharmacol. Bull.29(2), 321–326 (1993).
84.
GuyW: ECDEU assessment manual for psychopharmacology. Publication ADM. Vol. 76–338. National Institute of Mental Health, US Department of Health, Education and Welfare, Rockville, MD, USA (1976).
85.
SperoffLGlassRHKaseNG: Steroid contraception. In: Clinical Gynecologic Endocrinology and Infertility.Williams and Wilkins, Baltimore, MD, USA (1999).
86.
van GrootheestKVrielingT: Thromboembolism associated with the new contraceptive Yasmin. BMJ326(7383), 257 (2003).
87.
SheldonT: Dutch GPs warned against new contraceptive pill. BMJ324(7342), 869 (2002).
88.
DingerJCHeinemannLAJKuhl-HabichK: The safety of a drospirenone-containing oral contraceptie: final results from the European Active Surveillance study on Oral Contraceptives based on 142,475 women-years of observation. Contraception75, 344–354 (2007).
89.
PearceHMLaytonDWiltonLV: Deep vein thrombosis and pulmonary embolism reported in the Prescription Even Monitoring Study of Yasmin. Br. J. Clin. Pharmaco.60(1), 98–102 (2005).
90.
HeinemannLADingerJC: Range of published estimates of venous thromboembolism incidence in young women. Contraception75(5), 328–336 (2007).
91.
ShulmanL PGoldzieherJW: The truth about oral contraceptives and venous thromboembolism. J. Reprod. Med.48(11), 930–938 (2003).
92.
MishellDRJr: Cardiovascular risks: perception versus reality. Contraception59(1), 21S–24S (1999).
93.
SchurmannRBlodeHBendaNCroninMKufnerA: Effect of drospirenone on serum potassium and drospirenone pharmacokinetics in women with normal and impaired renal function. J. Clin. Pharmacol.46(8), 867–875 (2006).
94.
FoidartJM: Added benefits of drospirenone for compliance. Climacteric8(3), 28–34 (2005).
95.
RubigA: Drospirenone: a new cardiovascular-active progestin with antialdosterone and antiandrogenic properties. Climacteric6(3), 49–54 (2003).
