Hypogonadismagonadism and hypoactive sexual desire

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Although there are currently no established models of female sexual dysfunction in rats, there are several reasons to believe that such models could exist. The most obvious would be the consequences of hypogonadism induced by ovariectomy followed by maintenance with different doses of estrogen alone, or estrogen and progesterone. Ovariectomized rats treated with estrogen and progesterone display a complete pattern of procep-tive and receptive behaviors, whereas those treated with estrogen alone display no proceptive behaviors, low levels of lordosis, and high rates of rejection responses. Certain pharmacologic treatments (e.g. apomorphine, oxytocin, PT-141), are able to increase proceptive behaviors and reduce rejection responses in ovariectomized females treated or maintained on estrogen alone. This pattern of data suggests that such drugs may be useful in the treatment of hypoactive sexual desire disorder, with or without accompanying hypogonadism.

A similar loss of interest in sexual activity occurs during the phenomenon of "estrous termination". Estrous termination occurs progressively after the female receives a requisite number of intromissions and ejaculations during sex. It can also be induced by manual vaginocervical stimulation using a lubricated glass rod that approximates the size of a male rat penis, and that is inserted to mimic the stimulation received during intromission. The first behavioral set to disappear is solicitation, and this precedes a rise in rejection responses. Females given vaginocervical stimulation also show a faster loss of lordosis over the next 12 hrs, compared to females given sham stimulation. It would appear, then, that sexual stimulation in females, as in males, activates inhibitory systems that bring about refractoriness. It is not yet known how different pharmacologic treatments might delay the onset of estrous termination, and whether such effects might prove useful in treatment of low desire.

It will be important to consider how androgen administration may alter sexual behavior in ova-riectomized females, with or without estrogen treatment. Currently, combined androgen—estrogen treatment is used in postmenopausal women to restore sexual desire and arousal. It should be straightforward to examine this combined hormone therapy in ovariectomized rats and categorize the effects, along with studying potential mechanisms (e.g. steroid receptor activation and interaction, role of peripheral sex hormone binding globulins).

It will also be critical to study the sexual behavior of older female rats. Female rats have a homologue of "menopause" in which ovarian function is disrupted then declines to a continuous state of vaginal diestrus (accompanied by a progressive atrophy of the vagina and clitoris). It is not known how these females would respond to sexual advances by a male, or to manually applied vaginocervical stimulation.

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