Elsevier

Contraception

Volume 68, Issue 5, November 2003, Pages 339-343
Contraception

Original research article
Detection of raised FSH levels among older women using depomedroxyprogesterone acetate and norethisterone enanthate

https://doi.org/10.1016/j.contraception.2003.08.003Get rights and content

Abstract

The objective of this study was to investigate whether follicle-stimulating hormone (FSH) levels can be used reliably to indicate approaching menopause in older (aged 40–49), long-term users of depomedroxyprogesterone acetate (DMPA) and norethisterone enanthate (NET-EN). One-hundred and seventeen women using DMPA, 60 NET-EN users and 161 nonusers of contraception were recruited. At recruitment, serum FSH levels were measured and questions were asked regarding menopausal symptoms, menstrual cycle and date of last injection. Results of the recruitment blood test showed that 32% of the nonusers had FSH levels in the menopausal range >25.8 mIU/mL compared to 28% of the DMPA users and 9% of the NET-EN group. After adjusting for age, there was no significant difference between the 3 groups (p = 0.13). An increase of 1 year in age increased the FSH level by 3 mIU/mL (p < 0.001). All the hormonal contraceptive users were between 1 day and 12 weeks of their injection interval. Many had been using the injectable contraceptive method for over 10 years and almost all were amenorrheic at the time of recruitment. The data show that a raised FSH level can be detected during use of DMPA and NET-EN and could be used as a menopausal indicator without interrupting method use in this group of contraceptive users.

Introduction

Depomedroxyprogesterone acetate (DMPA) and norethisterone enanthate (NET-EN) are effective contraceptives with low failure rates [1]. One of the common side effects of these methods is amenorrhea, which increases in incidence over time [1]. In older users it may be difficult to distinguish between amenorrhea associated with approaching menopause and that induced by the method. Detection of menopause or perimenopause, therefore, presents a challenge in this group of contraceptive users. Traditional textbook management of an older woman using oral hormonal contraception recommends measurement of follicle-stimulating hormone (FSH) on the 7th day of the pill-free interval [2]. Advice for DMPA and NET-EN users is less clear; however, in the absence of data documenting efficacy, it has been suggested that they should change to a nonhormonal method of contraception, as menopausal symptoms will be masked, and measurement of FSH levels may be unreliable [2].

DMPA and NET-EN are known to inhibit the mid-cycle surge of FSH and luteinizing hormone (LH), but the tonic release of these gonadotrophins continues at luteal phase levels [3], [4]. A few studies have also shown that DMPA and NET-EN suppress raised FSH and LH levels in postmenopausal women [5], [6]. While limited information exists on the duration of the suppression of raised FSH and LH levels associated with menopause, in both these studies [5], [6], the lowest FSH and LH levels occurred between 14 and 30 days after injection. The majority of suppressed levels were still high enough to be classified as in the menopausal range. Thereafter, FSH and LH levels started to rise, and in one of these studies [6], FSH levels started rising back to presuppression levels between 40 and 80 days after injection.

In South Africa, hormonal injectable contraceptive use is high, with about 60% of Black African women practicing contraception using either DMPA or NET-EN [7]. Of the two available injections, older women almost exclusively use DMPA and often continue to use this method into their late 40s.

While the primary aim of this study was to investigate bone density in older women using hormonal contraceptives, a secondary objective was to investigate whether FSH levels could be used as an indicator of menopausal status in injectable users. This was due to the high prevalence of amenorrhea in the two injectable groups, which made it impossible to use the menstrual cycle as an indicator of menopausal status. This paper presents the results of the latter component of the study.

Section snippets

Materials and methods

A cohort of older women using DMPA (150 mg at 3-month intervals), NET-EN (200 mg at 2-month intervals), combined oral contraceptives (COCs) and nonusers of contraception were recruited from a large family-planning clinic in Durban, South Africa, between September 2000 and November 2001. For inclusion as an injectable user, women had to be aged between 40 and 49 years and had to have used the injectable hormonal contraceptive for at least 1 year. On recruitment, a questionnaire was administered

Results

In total, 117 DMPA and 60 NET-EN users were recruited. Fewer women were recruited in the NET-EN group, as this method is not as popular in older women. Baseline information about these women and 161 nonusers of contraception is summarized in Table 1. Nonusers of hormonal contraception were on average 2 years older than DMPA users (p < 0.001). NET-EN users were the youngest group with a mean age of 42.5 years. All women using either DMPA or NET-EN had been using the method for at least 1 year at

Discussion

Previous studies have been limited due to their small sample sizes and the inclusion of subjects who received only one dose of MPA or NET-EN [5], [6]. These studies concluded that the baseline values of FSH and LH in postmenopausal women declined from the day of injection to reach their lowest levels between 14 and 30 days and then rose back to presuppression levels between about 40 and 80 days postinjection. In one of these studies [5], one of the subjects received a second dose of NET-EN and

Limitations of the study

This study had a number of limitations. Subjects were part of another study which was not set up for taking multiple blood samples, which would be required to obtain an in-depth picture of gonadotrophin suppression. The researchers aimed to get subjects to come once during the peak gonadotrophin suppression period and once towards the end of a 2- or 3-month injection cycle. This was not always possible, as many women were only contactable by letter and it was therefore difficult to remind them

Acknowledgements

This study was supported by a grant from the World Health Organisation and The Department for International Development UK (DFID). We wish to acknowledge the Chemical Pathology Department at the Nelson R. Mandela Medical School of the University of Natal for performing the assays for the study, Mrs. Fikile Mbatha for coordination of the study. We would also like to thank Dr. Olav Meirik for his support in developing the protocol.

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