Combined Hormone Replacement in Menstrually-Related Mood Disorders
Condition: Premenstrual Syndrome; Depression
MeSH terms: Premenstrual Syndrome; Depression; Mood Disorders
Study type: Observational

Summary: 
      This study investigates the effects on symptoms of combined treatment with estrogen and
      progesterone in women with severe premenstrual syndrome (PMDD).

      Studies indicate that women with PMS experience improvement in symptoms following treatment
      with leuprolide acetate, when estrogen and progesterone levels are low. Women with PMS, but
      not women without the disorder, experience a return of symptoms within approximately a week
      after re-exposure to either estrogen or progesterone. The cause of this hormone-induced
      depression remains unclear. It is not known whether this depressed mood is due simply to the
      change in the levels of estrogen and progesterone and whether it would remit following
      continued exposure to stable levels of estrogen and progesterone. This study will determine
      whether the maintenance of stable hormone levels will prevent mood disturbances in women with
      PMS.

      Participants in this study will receive leuprolide acetate injections once a month for up to
      6 months. After 2 months, women whose symptoms have improved will receive a skin patch
      containing either estrogen or placebo (an inactive substance) and will be asked to take daily
      suppositories containing either progesterone or placebo. Women whose symptoms of PMS do not
      respond to leuprolide treatment after 2 months will end the study and be offered other
      treatment. Participants will be seen by a nurse in the clinic every two weeks and will fill
      out ratings and have blood drawn to measure hormone levels.
    

Detailed description: 
      Results from previous protocols (#90-M-0088 and 92-M-0174) have demonstrated that women with
      menstrually-related mood disorder (MRMD), but not women lacking this disorder, experience
      mood deterioration within approximately a week after exposure to either estradiol or
      progesterone in the context of gonadal suppression (induced by use of the depot gonadotropin
      releasing hormone agonist, leuprolide acetate). It is unknown whether this hormone-induced
      depression occurs consequent to changes in gonadal steroid levels or to simple exposure to
      levels above a critical threshold. Additionally, since the symptoms of depression stimulated
      by hormone addback appeared to remit by the fourth week of hormone administration, it is
      unclear whether continued administration of hormone would result in continued or repeated
      experience of depression or whether no further symptoms would appear subsequent to the
      initial precipitated episode. To address these points of uncertainty, we first will establish
      the efficacy of gonadal suppression in our MRMD subjects by administering depot leuprolide
      acetate for three months and then will administer both estradiol and progesterone in a
      continuous fashion for three months to determine whether maintenance of stable gonadal
      steroid levels will prevent the characteristic cyclic mood disorder.
    

Keywords: Depression; Menstrual Cycle; Gonadal Steroids; GnRH Agonist; PMS; Estradiol; Progesterone; Mood; MRMD; PMDD; Menstrually Related Mood Disorders