N Wahab, W Yusof, A Shuid, W Mahmoud, K Ali
estrogen, labisia pumila, ovariectomyt, postmenopause, reproductive hormones
N Wahab, W Yusof, A Shuid, W Mahmoud, K Ali. Labisia Pumila has Similar Effects to Estrogen on the Reproductive Hormones of Ovariectomised Rats.. The Internet Journal of Herbal and Plant Medicine. 2010 Volume 2 Number 1.
Introduction: The use of estrogen replacement therapy (ERT) in postmenopausal women has been linked to increased risks of endometrial and breast cancer. Labisia pumila (LP) which has been used traditionally for women’s health is a potential alternative agent for ERT. In this study we have compared the effects of LP aqueous extract to ERT (Premarin®) on reproductive hormones using ovariectomized rat model. Methods: Thirty-four ovariectomized rats were divided into five groups, A, B, C, D and E. Group A (the ovariectomized-control group) was given distilled water. Group B was given Premarin 0.07 mg/kg body weight. Groups C, D and E were given LP at doses of 17.5, 35.0 and 70.0 mg/kg body weight, respectively. All treatments were given by daily oral gavages. Blood samples were taken through the tails at 30, 60 and 90 days of treatment for plasma follicle stimulating hormone (FSH), estradiol, luteinizing hormone (LH), testosterone, androsteinedione and dehydroepiandrosterone sulphate (DHEA-S) analysis.Results: The results showed that 60-day treatment with LP at doses of 17.5 mg/kg body weight resembled the effects of Premarin whereby there were significant elevation of estrogen and testosterone levels, suppression of FSH and LH levels compared to ovariectomized-control group. The androsteindione and DHEA-S levels were not altered. Other doses or duration of treatment with LP gave inconsistent results. Conclusions:
LP has shown potential as alternative to ERT which would require further study. The equivalent human dose of LP should be considered based on the dose of 17.5 mg/kg body weight and 60 days of treatment in ovariectomized rats.
Menopause is defined as permanent cessation of the menstrual cycle due to the loss of ovarian follicular activities. It occurs naturally in women between the age of 45 to 52 years (1) or by total ovariectomy (2). The declining ovarian follicular activities in postmenopausal women resulted in decreased estrogen level (3,4,5). This is followed by a high FSH and LH levels due to loss of negative feedback by estrogen (3,6). The testosterone, androsteinedione and dehydroepiandrosterone levels were also lowered in postmenopausal women (7). Postmenopausal women may experience vasomotor symptoms such as hot flushes, night sweats, insomnia, emotional changes, lethargy, vaginal dryness, dyspareunia and urinary incontinence (8). The current treatment for postmenopausal symptoms and diseases related to estrogen deficiency is hormone replacement therapy (HRT) which contains estrogen and progestin. However, HRT has been shown to increase the risks of breast cancer (9, 10, 11) and endometrial cancer (10, 12). The risks of endometrial cancer can be reduced if progesterone is added to the HRT (10, 12) but this may further increase the risk of breast cancer (10, 11) and reduced the vasoprotective effects of HRT (13, 14). Following reports from Women’s Health Initiative (WHI) study that showed an increase risk of breast cancer among postmenopausal women who were using HRT, the prescriptions for HRT have declined rapidly. The WHI study reports were supported by s recent findings that the decline in the use of HRT may be related to the decline in the rate of new breast cancer cases (15). The age-adjusted breast cancer incidence rates in women in the United State fell 6.7% in 2003 (16).
In our quest to find alternative treatment to HRT, we have identified
The purpose of this study is to compare the effects of
Material and methods
Prior ethical clearance was obtained from the UKM Animal Care and Use Committee (PP/FAR/2009/NAZRUN/14JULY/267-JULY2009-MAY-2010) and the experiment was conducted at Animal Unit, Institute for Medical Research, Malaysia. Thirty female Sprague-Dawley rats, aged 10 to 13 months and weighing between 250 – 350 g were ovariectomized and randomly divided into 5 groups; ovariectomized-control (OVXC), estrogen replacement at 0.07 mg/kg body weight Premarin® (ERT),
Premarin® (Wyeth, Co. Kildare, Ireland) was crushed and dissolved in distilled water. Every 0.5 ml of gavage contained 0.07 mg/kg body weight of Premarin®. This dose was calculated based on the human dosage
Data analysis was performed using Statistical Package for Social Sciences software (version 16.0; SPSS Inc., Chicago). Data were tested for normality using Kolmgorov-Smirnov test. If the data was normally distributed, analysis of variance (ANOVA) with Tukey’s test was performed. For non-normally distributed data, non-parametric Kruskall-Wallis and Mann-Whitney U tests were performed and data were expressed as median and range.
The median estradiol levels for OVXC group at 30, 60 and 90 days of treatment were 26.59 (23.16-32.26), 18.21 (17.62 – 21.34) and 20.51 (17.05 – 24.44) pg/ml, respectively. As expected ERT group had consistently higher estradiol levels of 47.64 (40.04 – 95.59), 66.59 (34.32 – 111.32) and 24.90 (24.57 – 27.44) pg/ml, at the corresponding treatment period compared to OVXC group (p<0.05). There were no significant differences in the estradiol levels for all three
As for the FSH level, ERT group had lower FSH level of 53.37 (51.32 – 55.04) and 46.77 (32.67 – 62.14) ng/ml at 60 and 90 days of treatment respectively compared to ERT group (p<0.05). Surprisingly, all
LH levels for all the groups were similar at 30 days of treatment. ERT Group had a significantly lower plasma LH level compared to OVXC group (p<0.05) only at 90 days of treatment, whereas
Testosterone level for ERT group was raised at 60 days of treatment compared to OVXC group (p<0.05). Surprisingly,
Androsteinedione and DHEA-S levels for all groups at all duration of treatments were similar. On the other hand, both
In response to the WHI report, many physicians have recommended postmenopausal women to stop taking ERT. Prescription of Premarin® and Prempro®, the two most commonly prescribed HRT in the United States, had declined from 61 millions prescriptions in 2001 to 21 millions in 2004 (16). As the popularity of HRT continues to drop, postmenopausal women increasingly choose alternative forms (23).
Based on the effects of
It was also noticed from the results that the ovariectomized control group has minor variation in the estradiol levels. When Premarin® or
Of all the reproductive hormones, the most important hormone which needs attention is estradiol as this hormone is deficient in postmenopausal women and needs to be replaced. Premarin® has resulted in an increase in estradiol level as early as 30 days of treatment compared to 17.5 mg/kg body weight of
The negative feedback of the estrogenic effects on the hypothalamus and pituitary gland should have resulted in similar pattern for the other gonadotropins, LH. However, only
Testosterone is believed to play an important role in women’s libido (30,31). The drop in testosterone in postmenopausal women may be responsible for the loss of libido. In fact, women who had undergone ovariectomy showed significant loss of libido compared to natural occurring postmenopausal women as they have a more significant drop in testosterone level (32, 33). Similar to estrogen replacement therapy,
Authors would like to thank the Pharmacology and Physiology departments staff at UKM Medical Centre for their laboratory assistance.