Psychiatric complications of progesterone and oral contraceptives

J Clin Psychopharmacol. 1981 Nov;1(6):350-67. doi: 10.1097/00004714-198111000-00003.


Progesterone plays a critical role in the menstrual cycle, pregnancy, and sexuality. Its role in premenstrual syndrome, dysmenorrhea, and postpartum disorders is outlined. Oral contraceptives seem to affect mood and behavior in some women without preexisting psychiatric illness, sometimes inducing depression and loss of libido. When used as psychotropic agents, they can have mood-stabilizing effects and relieve premenstrual syndrome.

PIP: The effects of progesterone on the central nervous system and target organs are described along with its role in reproductive functions. The literature relating to mood and behavioral changes associated with progesterone, progestins, and oral contraceptives (OCs) is summarized and reviewed, and the role of progesterone in the phenomena described is examined. The role of progesterone and the progestins in producing mood and behavioral change is still essentially unknown. On the basis of available data the following is postulated: progestins are a likely causal factor in the depression and loss of libido assoicated with OCs. A falling level of progesterone is a possible causal factor in the premenstrual syndrome and in postpartum disorders. It plays a limited or no role in mood and behavioral changes associated with menarche, menopause, and involutional melancholia. The mechanism of action to account for decreased sexual behavior, depression, and fatigue is highly speculative. It may be a combination of progesterone's sedative effects, decreases in monoamine levels, and depressive action on cerebral metabolism. The mechanism to account for decreases in anxiety, irritability, negative affect, and increased activation is also speculative. Its mood-stabilizing action may be a combination of its anticonvulsant effect, depression of neuronal arousal level, and inhibition of stimuli, originating in the hypothalamus and reticular formation, which are going to the cortex. Most women using OCs for their contraceptive properties can expect minimal change in mood and sexual behavior. It is unknown whether OCs cause depression, but interpretation of the data in the literature does not support such an association. For women who have experienced severe premenstrual tension in the absence of other psychiatric illness, OCs may prove useful. The choice of OC would depend on the presence/absence of a history of premenstrual irritability. For women with psychoses with premenstrual exacerbation, OCs may have a place as a part of a regimen including lithium and/or antipsychotic medications. Needed at this time are carefully controlled experiments with progesterone and other hormones in humans, on a prospective basis, over a long period of time, with correlations with neurophysiological and endocrinological measures and employing crossover and double-blind techniques.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Adult
  • Affective Symptoms / chemically induced*
  • Animals
  • Brain / drug effects
  • Cardiovascular System / drug effects
  • Contraceptives, Oral / adverse effects*
  • Contraceptives, Oral / therapeutic use
  • Female
  • Genitalia, Female / drug effects
  • Humans
  • Male
  • Menopause / drug effects
  • Menstruation / drug effects
  • Middle Aged
  • Pregnancy
  • Premenstrual Syndrome / drug therapy
  • Progesterone / adverse effects*
  • Progesterone / pharmacology
  • Progesterone / physiology
  • Psychoses, Substance-Induced / etiology*
  • Psychotic Disorders / drug therapy
  • Puerperal Disorders / drug therapy
  • Sexual Behavior / drug effects


  • Contraceptives, Oral
  • Progesterone