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Testosterone and Sexual Behavior in Oral Contraceptive Users and Nonusers: A Prospective Study GERIANNE

*Department Reproductive

M. ALEXANDER,*

BARBARA B. SHERWIN,*” AND DAVID W. DAvIDsoNt

of Psychology, McGill University, Biology Unit, Center for Reproductive

Montreal, Biology,

JOHN BANcRoFT,t

Canada; and TMRC Edinburgh, Scotland

The relationship between plasma testosterone (T) secretion and patterns of sexual behavior was examined in 18 women using oral contraceptives (OCs) and 13 nonusers matched for partner availability. Retrospective assessments of perimenstrual symptoms, sexual attitudes, and sexual experience were obtained and women completed daily ratings of the frequency of sexual activities and the level of well-being for 1 month. Plasma levels of sex hormone binding globulin (SHBG), progesterone, Total T, Free T, and non-SHBG bound T were determined by radioimmunoassay at four phases of the pill or menstrual cycle. Overall, women not using OCs had higher plasma levels of Total, Free, and non-SHBG bound T and lower plasma levels of SHBG than those of OC users. Further, only nonusers had perimenstrual decreases in plasma levels of Total and Free T. The two groups were comparable on most retrospective measures. However, OC users reported more satisfaction with their sexual partners than did nonusers and prospective monitoring revealed that they engaged in sexual interactions more frequently than did nonusers across the cycle. In contrast, both groups reported a similar frequency of autosexual activities across the cycle. There were no correlations between average levels of T and levels of sexual desire, sexual interactions, or autosexuality. Moreover, only nonusers reported a decrease in levels of sexual desire during the perimenstrual period that was associated with the changes in Free T over the menstrual cycle. D 1990 Academic press, IK.

Evidence that testosterone (T) stimulates specific aspects of female sexual behavior came from a report showing that when administered alone or in combination with estradiol (EJ to surgically menopausal women, T increased sexual desire and the frequency of sexual fantasies (Sherwin, Gelfand, and Brender, 1985). This androgenic enhancement of sexual motivational behaviors was also apparent in oophorectomized women who had been receiving a preparation of E2 and T for at least 2 years (Sherwin and Gelfand, 1987). ’ To whom correspondence should be addressed at Department of Psychology, McGill University, 1205 Dr. Penfield Avenue, Montreal, Quebec, Canada H3A 1Bl. 388 0018-506X/!Xl $1 SO Copyright All rights

0 1990 by Academic Press, Inc. of reproduction in any form reserved

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Other researchers have reported positive associations between T and sexual behavior in younger cycling women (Bancroft, Sanders, Davidson, and Warner, 1983; Bancroft, Davidson, Warner, and Tyrer, 1980; Persky, Dresibach, Miller, O’Brien, Khan, Lief, Chamey, and Strauss, 1982; Schreiner-Engel, Schiavi, Smith, and White, 1981; Morris, Udry, KhanDawood, and Dawood, 1987). However, neither the direction nor the strength of association between a specific measure of T (e.g., midcycle levels, average levels across the cycle) and a specific behavior (e.g., masturbation frequency, sexual arousal) is consistent across these investigations. Most research on the relationship between T and female sexual behavior has relied on the measurement of Total T, which is a global measure of the amount of the hormone in plasma. Total T includes the portion of T that is bound to sex hormone binding globulin (SHBG), the portion that is bound to albumin, and unbound or Free T (about 2%). Only Free T and T bound to albumin are considered capable of exerting biological effects (Manni, Pardridge, Cefalu, Nisula, Bardin, Santner, and Santen, 1985). Because the ratio of active to inactive hormone varies according to the concentration of SHBG in plasma (Vermeulen, 1983), individuals with similar plasma levels of Total T may actually have differing amounts of biologically available hormone. Thus, measurement of only Total T may not permit an accurate assessment of the relationship between specific parameters of T and sexual behaviors. Nonhormonal factors may also affect the reliability of an association between T and female sexual behaviors. The positive correlation between sexual feelings and well-being in women (Bancroft et al., 1983; Warner and Bancroft, 1988) suggests one important source of variability. Moreover, attitudes toward sexuality may override any hormonal effects on sexual behavior (Bancroft et al., 1983). The need to assess and control for these possible confounds in human psychoendocrine studies is therefore clear. It has recently been suggested that cyclicity of T release may play an important role in the expression of female sexual behavior (Sherwin, 1988). In ovulating women, plasma T levels rise around midcycle and fall premenstrually (Vermeulen and Verdonck, 1976; Judd and Yen, 1973; Bancroft et al., 1983). One source of the midcycle rise in T is the increase in ovarian androgen secretion which occurs under the influence of high luteinizing hormone (LH) levels at that time (Vermeulen, 1983). Oral contraceptives (OCs) are thought to instate a tonic pattern of T secretion across the pill cycle. These compounds suppress follicle-stimulating hormone and LH, resulting in diminished ovarian secretion of T at midcycle (Wiebe and Morris, 1984). Thus, the comparison of women using and not using OCs provides a useful model for clarifying the relationship between cyclicity or tonicity of T secretion and female sexual behavior. There is some evidence that the expression of sexual behavior across

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TABLE 1 Composition of Oral Contraceptive Tablets Taken by Women in the OC Group n Combined preparations Min-Ovral Ortho-Novum l/50 Phased preparations* Triphasil Ortho 777

Progestogen (mg)

Estrogen (pg)

3 1

0.15 NOR 1.0 NET

30 EE 50 EE

9 5

0.05/0.075/0.125 NOR 0.5/0.75/1.00 NET

30/40/30 EE 35 EE

Note. NET, norethindrone; NOR, d-norgestrel; EE, ethinyl estradiol. * Levels of hormone in active tablets vary across the 21 days.

pill and menstrual cycles is consistent with differences in endogenous T secretion. Adams, Gold, and Burt (1978) found a midcycle peak in the frequency of autosexual activities across the menstrual cycle that was not apparent during the pill cycle. Furthermore, a retrospective study of over 3000 women found that women not using OCs were more likely to report fluctuations in their levels of sexual desire across the cycle than OC users (Warner and Bancroft, 1988). The goal of the present study was to assess the association between sexual behavior and T levels while attempting to control for other factors that might have affected this hormone-behavior relationship. In this prospective investigation, a group of OC users and nonusers was matched for availability of a partner, and assessed for sexual attitudes and fluctuations in well-being across the pill and menstrual cycles. Plasma levels of biologically available T as well as Total T were measured at several points during the cycle concurrent with behavioral monitoring. It was hypothesized that there would be an association between sexual behaviors and the pattern of T release in both OC users and nonusers. METHOD Subjects Subjects were undergraduate students at McGill University who responded to recruitment posters, to advertisements placed in the student newspaper, and to appeals made during several psychology classes. Eighteen OC users and 15 women not currently using OCs agreed to participate in the prospective study. All 33 women were between the ages of 18 and 28 and had a regular, available, male sexual partner. An available partner was defined as someone with whom daily sexual interactions were possible. None of the women were using prescribed medications (other than OCs) and none had a diagnosed medical, psychiatric, or gynecological problem. All OC users were using their current brand for at least three menstrual cycles. Table 1 presents a summary

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of the types of OCs used by these women. Nonusers reported regular menstrual cycles of 26-35 days in length and no history of OC use for at least the three previous menstrual cycles. Methods of contraception used by the nonpill group included IUD (n = 2), condoms (n = 5), diaphragm (n = 2), and rhythm (n = 3). Three women in the nonpill group used no contraceptive method as their sexual activities with male partners did not include sexual intercourse. Written informed consent was obtained from all participants who were paid $25 at the completion of the study. Procedure

Each woman was seen on four occasions. No attempt was made to have women enter the study at the same pill week or menstrual phase. For nonusers, cycle phase was estimated according to the day of onset of the last menstruation and confirmed later by the hormone assays. Nonusers were seen during the estimated premenstrual week, menstrual week, postmenstrual (Days 7 to 13 after the onset of menses), and midcycle/early luteal (reverse cycle days -14 to -7) phases. OC users were seen at weekly intervals. During the first meeting, information concerning menstrual, sexual histories, and sexual attitudes was obtained. Subjects were then given the daily self-report forms and were instructed to complete one record at approximately the same time each day for a period of 30 days. Completed forms were returned weekly at each test session. Behavioral

Assessments

The retrospective assessment was based on three questionnaires. A menstrual history questionnaire (MHQ) contained information on women’s menstrual and contraceptive histories including sexual activity during menstruation. The premenstrual assessment form (PAF) (Halbreich, Endicott, Schacht, and Nee, 1982), describes women’s experience of premenstrual mood and physical changes in terms of symptom clusters and measures of symptom severity. The third questionnaire, the sexual experience scales (SES) (Frenken and Vennix, 1981), describes four dimensions of sexual experience. The sexual morality scale (SES-1) assesses premarital sexual experiences and associated attitudes. The psychosexual stimulation scale (SES-2) assesses the extent to which an individual seeks or allows sexual stimuli in the form of erotic imagery, the degree of arousal to erotic imagery, and interpersonal sexual attraction. The sexual motivation (SES-3) and the attraction to marriage (SES4) scales describe the sexual and social relationship with a partner in terms of the degree of sexual attraction, sexual satisfaction, and the strength of the social and emotional bond to the partner. Prospective monitoring of well-being and sexual behavior was accomplished by the daily forms. Women were asked to rate their perceived

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level of sexual desire on a 7-point Likert scale and were required to document the occurrence of sexual daydreaming, masturbation, and sexual interactions with a partner (excluding/including intercourse) for each day on separate rating scales. Other items required subjects to indicate any self and/or partner attempts to initiate sexual interactions and to rate their experience of 13 mood and physical change items on O-5 Likert scales. Hormonal

Measurement

Twenty milliliters of blood was taken between 12:OO PM and 2:00 PM at each of the four test sessions. The blood was immediately centrifuged and the plasma stored at - 20°C. At the completion of the study, plasma determinations were carried out by radioimmunoassay for sex hormone binding globulin (Anderson, Lesley, Fisher, Shepherd, Newman and Hendrecks, 1976), Total T (Corker and Davidson, 1978), Free T (Hammond, Nisker, Hones, and Siiteri, 1980), and non-SHBG bound T (Tremblay and Dube, 1974). Non-SHBG bound T includes both Free T and the portion of T that is bound to albumin. Plasma progesterone (P) levels determined by radioimmunoassay (Ratcliffe, Corrie, Dalziel, and Macpherson, 1982) were used to assess luteal function in the non-pill users. A plasma P level greater than 20 nmole/liter between days 18 and 24 of the menstrual cycle was regarded as evidence of ovulation. Statistical Analyses The retrospective questionnaires were analyzed using Student’s t tests and Chi-squares when appropriate. Hormone levels were analyzed using a two-way analysis of variance (group by phase) with repeated measures. Newman-Keuls method of multiple comparisons was used to explore group by phase interaction effects when they occurred. Hormone-behavior relationships were examined using Pearson correlational analyses. Consecutive daily ratings of each item on the questionnaire were analyzed using two-group discriminant analyses. In addition, two-way analyses of variance (ANOVA) (group by phase) with repeated measures over time were performed on the weekly mean scores for each sexual and physical item. RESULTS Subject Characteristics The criteria for ovulation were clearly met in all but two nonusers who were subsequently dropped from the study. Table 2 presents a summary of subjects characteristics. All women were nulliparous with the exception of a single woman in the pill group who had one child. There were no group differences in the MHQ items, the PAF symptom

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TABLE 2 Characteristics of Subjects Based on the Retrospective Questionnaires

Age (years) Age of first menses Cohabiting Use of medication for Premenstrual complaints (n) Menstrual complaints (n) Subjects who masturbate (n) Increased sexual activity/interest premenstrually (PAF: l-6) SES-1 Sexual morality SES-2 Psychosexual stimulation SES-3 Sexual motivation SES-4 Attraction to marriage

(mean, SE)

OC users (n = 18)

Nonusers (n = 13)

21 (0.41) 14.0 (0.48) 5

22.57(0.84) 12.2(0.25) 3

6 3 16

5 2 11

3.1 (0.25)

1.7 (0.22)**

-0.98(0.01) - l.lS(O.03)

- 0.86(0.01)

-0.30(0.03) -0.39(0.04)

- 2.03(0.10)*

Note. SES scales: higher score = more negative evaluation of that dimension sexuality. * Significantly different from OC-users at P < 0.05. ** Significantly different from OC-users at P < 0.01.

of

categories, or measures of symptom severity. However, the PAF revealed that OC users reported a greater increase in sexual interest/activity during the premenstrual period than the nonusers (t(29) = 2.9, P < 0.05). There was no significance between group differences on the SES-2 (psychosexual stimulation) subscale. The two groups of women were comparable in terms of the number who masturbated and the percentage who engaged in intercourse during menstruation. However, OC users were more permissive both in terms of their attitudes toward premarital sexual contacts (SES-1: t(29) = 2.67, P < 0.05) and in their sexual interactions with their partners (SES-3: t(29) = 3.56, P < 0.01) than were nonusers. Prospective Assessment

It was possible to assess the midcycle, premenstrual, and menstrual weeks of the same cycle in all women. In the majority of women, the data for the postmenstrual week were derived from the subsequent menstrual cycle. Information on the postmenstrual week was not available for two women in the pill group. Thus, there were 18 women in the pill

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group and 13 women in the nonpill group for the remaining analyses, except when the postmenstrual week was included in the analyses. In that case, data was provided by 16 OC users and 13 nonusers. A. Hormone Levels There were group differences between the average levels of SHBG (F(1, 27) = 12.93, P < 0.001) and non-SHBG bound T (F(1, 27) = 5.35, P < 0.05) across the pill or menstrual cycle. Nonusers had lower levels of plasma SHBG and higher levels of non-SHBG bound T than those of OC users (44.5 nmole/liter SE = +3.7 vs 92.5 nmole/liter SE = 27.4 and 107.2 pg/ml SE = k9.9 vs 69.1 pg/ml SE = rlr6.3, respectively). There were group by phase effects on Total T (F(3, 81) = 3.69, P < 0.05) and Free T (F(3, 81) = 5.88, P < 0.001) levels. Nonusers had higher levels of Total T during the postmenstrual week and midcycle phase when compared to those of OC users at comparable points in time (P < 0.01). In nonusers, levels of Total T during the menstrual week were lower than Total T levels during the postmenstrual and midcycle phase levels (P < 0.01). Although levels of Free T remained higher in nonusers than in OC users across the cycle (P < O.Ol), Free T was lower during the menstrual week than it was during the midcycle (P -=c0.01) and postmenstrual phases of the nonpill cycle (P < 0.05) (Fig. 1). B. Daiiy Questionnaire 1. Mood and physical sensation items. There were few increases in the severity of psychological symptoms across the midcycle to menstrual weeks (Table 3). Both groups reported premenstrual increases in their ratings of mood swings @‘(I, 27) = 5.47, P < O.Ol), but only nonusers experienced lower energy levels during the perimenstrual period (F(3, 81) = 2.85, P < 0.05). Discriminant analyses performed on the 21 consecutive days of the pill and menstrual cycles from midcycle to the end of the menstrual week revealed that OC users reported less anxiety on the last day of the premenstrual week than did nonusers (eigenvalue = 5.12, P < 0.05). An evaluation of the combined psychological change score, which represents the average rating of all psychological changes, revealed that nonusers’ symptom scores were lower during the postmenstrual week than at any other time in cycle (P < 0.05). Further, nonusers’ ratings of psychological symptoms during the postmenstrual week were significantly lower than the ratings of OC users at that time (P < 0.05) (Fig. 2). Both groups reported mild increases in the severity of physical symptoms during the perimenstrual period (Fig. 2). There was a group by phase effect on the combined physical change scores (F(3, 81) = 7.50, P < 0.01). The averaged rating of all physical symptoms showed that, relative to midcycle ratings, nonusers experienced significant physical

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Testosterone and sexual behavior in oral contraceptive users and nonusers: a prospective study.

The relationship between plasma testosterone (T) secretion and patterns of sexual behavior was examined in 18 women using oral contraceptives (OCs) an...
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