Treatment of Symptoms of Premenstrual Dysphoric Disorder
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.
Premenstrual disorders, including premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD), are cyclic luteal-phase events that encompass physical, psychological and behavioral symptoms. For PMS, these symptoms range from moderate to severe. PMDD, by definition, is a severe form of PMS characterized as a distinct affective disorder that causes social and/or occupational impairment. It has been estimated that 20-40% of ovulatory women have symptoms that can be classified as PMS, whereas 3-8% of reproductive women have symptoms that meet criteria for PMDD.
The criteria for both PMS and PMDD stipulate that symptoms must be present during the 5 days prior to menses, resolve by the end of menses, occur for at least 2-3 consecutive menstrual cycles, and not be an exacerbation of an underlying medical or psychiatric disorder. The diagnosis of PMDD is outlined in the Diagnostic and Statistical Manual for Mental Disorders ( Box 1 ). Since there is no specific assay to diagnose these disorders, prospective daily rating by the patient is imperative in the diagnostic process. There is currently no general accepted consensus regarding the diagnostic criteria for PMS other than those of the American College of Obstetricians and Gynecologists (ACOG), although these criteria were generally reaffirmed by a recent expert panel convened to refine the criteria for the diagnosis of PMS. ACOG criteria require one or more bothersome affective or somatic symptoms, including irritability, depressed mood, angry outbursts, anxiety, confusion, social withdrawal, breast tenderness, abdominal bloating, headache and swelling of extremities, which interfere with social or occupational domains.
PMS and PMDD share a complex psychoneuroendocrine etiology hypothesized to involve alterations in neurotransmitter systems and neuropeptides, including but not limited to the serotonin, γ-amino butyric acid (GABA), and endogenous opioids. However, clinically, the symptoms are triggered by the rise and fall of estrogen and progesterone related to ovulation in genetically or otherwise predisposed individuals. PMS-like symptoms can also be evoked by exogenous steroid (estradiol or progesterone) administration in women with PMS, but not control women.
An obvious therapeutic approach to reliably produce anovulation is the combined estrogen/progestin-containing contraceptive pill (COC). COCs have long been indicated as a safe, reversible form of contraception, but the evolution of the pills' active ingredients has allowed them to be considered for the treatment of cycle-related disorders such as PMS and PMDD. The new class of COCs that has been recently shown to be effective for treating PMDD contains a low dose of ethinyl estradiol and a new progestin called drospirenone in a novel dose regimen. Drospirenone is related to the diuretic spironolactone and has anti-androgenic and anti-aldosterone properties. Shortening the pill-free interval from 7 to 4 days provides better suppression of endogenous steroid production.
Abstract and Introduction
Abstract
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.
Introduction
Premenstrual disorders, including premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD), are cyclic luteal-phase events that encompass physical, psychological and behavioral symptoms. For PMS, these symptoms range from moderate to severe. PMDD, by definition, is a severe form of PMS characterized as a distinct affective disorder that causes social and/or occupational impairment. It has been estimated that 20-40% of ovulatory women have symptoms that can be classified as PMS, whereas 3-8% of reproductive women have symptoms that meet criteria for PMDD.
The criteria for both PMS and PMDD stipulate that symptoms must be present during the 5 days prior to menses, resolve by the end of menses, occur for at least 2-3 consecutive menstrual cycles, and not be an exacerbation of an underlying medical or psychiatric disorder. The diagnosis of PMDD is outlined in the Diagnostic and Statistical Manual for Mental Disorders ( Box 1 ). Since there is no specific assay to diagnose these disorders, prospective daily rating by the patient is imperative in the diagnostic process. There is currently no general accepted consensus regarding the diagnostic criteria for PMS other than those of the American College of Obstetricians and Gynecologists (ACOG), although these criteria were generally reaffirmed by a recent expert panel convened to refine the criteria for the diagnosis of PMS. ACOG criteria require one or more bothersome affective or somatic symptoms, including irritability, depressed mood, angry outbursts, anxiety, confusion, social withdrawal, breast tenderness, abdominal bloating, headache and swelling of extremities, which interfere with social or occupational domains.
PMS and PMDD share a complex psychoneuroendocrine etiology hypothesized to involve alterations in neurotransmitter systems and neuropeptides, including but not limited to the serotonin, γ-amino butyric acid (GABA), and endogenous opioids. However, clinically, the symptoms are triggered by the rise and fall of estrogen and progesterone related to ovulation in genetically or otherwise predisposed individuals. PMS-like symptoms can also be evoked by exogenous steroid (estradiol or progesterone) administration in women with PMS, but not control women.
An obvious therapeutic approach to reliably produce anovulation is the combined estrogen/progestin-containing contraceptive pill (COC). COCs have long been indicated as a safe, reversible form of contraception, but the evolution of the pills' active ingredients has allowed them to be considered for the treatment of cycle-related disorders such as PMS and PMDD. The new class of COCs that has been recently shown to be effective for treating PMDD contains a low dose of ethinyl estradiol and a new progestin called drospirenone in a novel dose regimen. Drospirenone is related to the diuretic spironolactone and has anti-androgenic and anti-aldosterone properties. Shortening the pill-free interval from 7 to 4 days provides better suppression of endogenous steroid production.