91140949 The impact of different doses of estrogen and progestin on mood and sexual behavior in postmenopausal women

Abstract

This study investigated the effects of various doses of estrogen and progestin on psychological functioning and sexual behavior of 48 healthy, naturally menopausal women. Subjects were tested before treatment and then randomly assigned to 1 of 4 cyclic sequential hormone regimens for 1 yr. Groups A and C received 0.625 or 1.25 mg conjugated equine estrogen (CEE), respectively, for days 1-25 and 5 mg medroxyprogesterone acetate from days 15-25. Groups B and D were given 0.625 or 1.25 mg CEE, respectively, from days 1-25 and placebo from days 15-25. The higher dose of CEE induced supraphysiological levels of plasma estrone. Plasma testosterone levels were lower in group A when blood was sampled during days 18-20 at a time when they were ingesting both 0.625 mg CEE and 5 mg medroxyprogesterone acetate (P < 0.05), although these decreases were perhaps too trivial to have affected sexual behavior as was hypothesized. Women in group A also had more negative moods and more psychological symptomatology during treatment compared to those in jjroup D who were receiving 1.25 mg CEE and placebo (P < 0.0 L). Regardless of group, sexual desire and arousal were higher during the first 2 weeks of the treatment cycle than during wi;ek 4 when no hormones were being ingested (P < 0.05). Thesu findings demonstrate that the effects of progestin on the cential nervous system are reflected by an increase in psychological, exclusive of sexual, symptomatology and are attenuated by a higher estrogen/progestin dose ratio. (J Clin Endocrinol Metab 72: 336-343,1991) T INCREASING tendency to treat postmenopausal women with estrogen-progestin replacement regimens has prompted numerous anecdotal reports of adverse progestational effects on mood, sexuality, and physical symptoms. The observation that progestins have sedative and hypnotic properties in humans was first reported by Selye in 1942 (1). Since then, it has been established that progestins have potent anaesthetic properties and that the administration of large doses to humans induces dizziness, drowsiness (2), and deep sleep (3). 17a-Hydroxyprogesterone derivatives possess high progestational potency and exert antiandrogenic effects (4). In addition, progestins decrease brain excitability, thereby raising the electroshock seizure threshold (5), whereas estrogens have the opposite effect on brain electrical activity (6). These two steroid hormones also exert contrary effects on monoamine oxidase (MAO), the enzyme that catabolizes the neurotransmitter serotonin. Whereas estrogen decreases MAO activity in the amygReceived July 5,1990. Address all correspondence and requests for reprints to: Dr. B. B. Sherwin, Department of Psychology, McGill University, 1205 Docteur Penfield Avenue, Montreal, Quebec, Canada H3A 1B1. * This work was supported by Ayerst, McKenna, and Harrison, Inc., Canada, and Grant MA-8707 from the Medical Research Council of Canada (to B.B.S.). dala and hypothalamus (7), progestins increase it (8). Thus, with respect to postmenopausal replacement therapy, it was hypothesized :hat the influence of these two sex steroids on behavior might depend on the relative doses of each as well as the specific compounds administered. The major goals of the present study were to investigate the clinical effects of adding a 17-hydroxyprogesterone derivative, medroxyprogesterone acetate (MPA), to various doses of conjugated equine estrogen (CEE) on mood and sexual behavior of postmenopausal women within the context of a prospective experimental design. Materials and Methods