PMS and OCs

RUNNING HEAD: Why do women on OCs experience PMS?

Answering the Question: If combined oral contraceptives work by keeping a woman’s

hormonal cycle from fluctuating, thereby preventing ovulation, why do women taking the

pill still suffer from PMS?

Travis Sky Ingersoll

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PMS and OCs

If combined oral contraceptives work by keeping a woman’s hormonal cycle from

fluctuating, thereby preventing ovulation, why do women taking the pill still suffer from

PMS?

Before exploring the role of contraceptive use in relation to premenstrual syndrome

(PMS), it is best to provide an overview of the definition of PMS, what causes its

symptoms, and what treatments are currently available to ameliorate symptoms. A brief

review of how oral contraceptives (OCs) work is given in order to help understand OCs

role in producing symptoms of PMS. We will conclude with a brief review of new OCs

that promise to virtually eliminate menstruation and possibly even PMS.

What exactly is premenstrual syndrome? A syndrome is a group of symptoms that

occur together, and in the case of PMS those symptoms are in relation to the female’s

menstrual cycle. With PMS, physical symptoms may include cramps, dizziness,

backache, fatigue, nausea, a tingling in the extremities, abdominal bloating, breast

tenderness, breast swelling, change in appetite, thirst, edema, and increased body weight.

Psychoemotional symptoms may include anxiety, tension, irritability, depression, mood

swings, crying spells, decreased interest, insomnia, feeling out of control, and an

inability to concentrate (Backstrom et al., 2003; Hatcher, 2004; Jones & Lopez, 2006).

For women whose PMS symptoms have a significant, negative impact on their daily life,

a diagnosis of premenstrual dysphoric disorder (PMDD) could be made according to the

criteria set by the American Psychiatric Association’s DSM-IV (1994).

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PMS and OCs

How many women suffer from premenstrual syndrome? According to Jones and

Lopez (2006) around 70% - 90% of women suffer from some kind of physical and/or

emotional symptoms associated with their menstrual cycle. Around 20% to 30%

experience moderate to severe PMS, while another 1% - 10% are debilitated by the

severity of their symptoms (Hatcher et al., 2004).

What mechanisms cause premenstrual syndrome? The truth of the matter is that

nobody really knows what the exact mechanisms underlying many of the symptoms

associated with PMS are. However there are a number of researched-backed theories

which offer some insight on this physiological/psychoemotional phenomenon. PMS is

understood as a result of various neurochemical and physiological interactions that take

place due to the cyclic dispersal of gonadotropins. Due to the interactions between the

brain and secreted hormones, it is generally agreed that the ovaries, and in particular the

corpus luteum, are at the root of PMS (Backstrom et al., 2003; Freeman et al., 2001;

Jones & Lopez, 2006).

The corpus luteum forms in the follicular cavity left by the expelled egg during

ovulation. This process occurs during the second half of the menstrual cycle. Lutenizing

hormone (LH) peaks during ovulation and is understood to be the primary compound

responsible for the formation and function of the corpus luteum, which is to secrete

progesterone and estradiol (Jones & Lopez, 2006). The hormones secreted prime the

uterus for the possible implantation of a fertilized ovum. If the egg is not fertilized the

corpus luteum disintegrates, during which time PMS symptoms also disappear (Freeman

et al., 2001). If however, fertilization does occur, the corpus luteum continues producing

progesterone and estradiol until the developing embryo takes over the process of

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PMS and OCs

hormone secretion. Research has found that during anovulatory cycles, such as those

induced by the use of some oral contraceptives, or for any other reason, the corpus

luteum is not formed and PMS symptoms are either improved or absent (Hamarback &

Backstom, 1988; Mortola, Girton, & Fisher, 1991).

Estradiol, progesterone and progesterone metabolites appear to be the primary

catalysts for experiencing PMS in susceptible women. We mention PMS susceptibility

due to the fact that not every woman will ever experience PMS, and research has shown

no difference in progesterone and estradiol levels between women who suffer from PMS

and those who do not (Backstrom et al., 2003). With regard to PMS, levels of estradiol

and progestogens appear to affect the GABA and serotonin systems, but also have been

shown to influence norepinephrine and endorphin production (Jones & Lopez, 2006).

How this gonadotropin influence on the GABA system and serotonin levels works to

produce symptoms of PMS is not completely understood yet. However, when women

suffering from PMS are given selective serotonin reuptake inhibitors (SSRIs), a

significant decrease in PMS symptoms is produced (Kouri, E. M. & Halbreich, U., 1997).

What treatment options are available for PMS? As was mentioned, SSRIs have

been shown to be effective in treating the psychoemotional symptoms of PMS, and have

been shown to improve some women’s physical symptoms as well (Hatcher et al., 2004).

Of course the specific kind of SSRI used, such as fluoxetine (Prozac), alprazolam

(Xanax), or sertraline, would impact the specific symptoms alleviated. With regard to

dosage, SSRIs have been found to be effective when taken continuously, but also can be

taken in a cyclic manner, such as only during the last 14 days of the menstrual cycle

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PMS and OCs

(Backstrom et al., 2003; Hatcher et al., 2004). However, one of the most common side

effects of using SSRIs is sexual dysfunction.

Another route in the treatment of PMS is administering high doses of gonadotrophin-

releasing hormone (GnRH) agonists (Jones & Lopez, 2006). The use of GnRH agonists

result in extremely low progesterone and estrogen blood serum levels, thereby causing a

reduction in the secretion of follicle-stimulating hormone (FSH) and LH by the pituitary

gland (Freeman et al., 2001). Due to the reduction of FSH and LH, anovulation and

amenorrhoea result. Anovulation means not ovulating, while amenorrhoea refers to a

cease of menstruation. Both physiological and psychoemotional symptoms are alleviated

using this method of treatment. The primary drawbacks of using GnRH agonists in the

treatment of PMS are a loss of bone density, possible impairment in cognitive

functioning, and postmenopausal symptoms (Backstrom et al., 2003).

Surgical oophorectomy is yet another option. Performing an oophorectomy means that

the ovaries are completely removed. Although this treatment method for PMS is drastic

and should only be used when all other options have been exhausted, substantial

reduction of symptoms have been documented (Backstom et al., 2003).

It should be mentioned that many of the treatment options being reviewed are intended

to treat severe forms of PMS, there are many less-drastic options available as well.

Exercise and dietary manipulations have also been shown to reduce symptoms for those

experiencing mild forms of PMS. Minimizing consumables such as alcohol, caffeine,

sugar and salt have been found to help (Jones & Lopez, 2006). Vitamin therapy has also

shown promise. In particular, vitamin B6 has shown to produce significant improvement

in PMS symptoms (Abraham & Hargrove, 1980). However, other studies have indicated

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PMS and OCs

no such improvement using vitamin B6 (London & Bradley, 1991). Of course there’s

always Midol.

In addition there has also been research pointing to the effectiveness of an extract of

the chaste tree or chasteberry. In a randomized, placebo controlled study by Schellenberg

(2001), 178 women who experience PMS were either given a chasteberry tablet or a

placebo pill once daily. Participants taking the chasteberry tablets communicated a

significant improvement in PMS symptoms on 5 of the 6 self-assessment items.

Alleviated symptoms included irritability, anger, mood-alteration, headache and breast

fullness. The only symptom not relieved was bloating (Huddleston & Jackson, 2001).

To begin to answer the question posed at the beginning of this paper, we will now

review the use of oral contraceptives in the treatment of PMS. Theoretically, oral

contraceptives should decrease PMS symptoms since they inhibit ovulation. This is

accomplished by giving the female body a constant, and somewhat elevated, dose of

estrogen, progesterone, or a combination of both (Jones & Lopez, 2006). Estrogen

inhibits ovulation, while progesterone thins the endometrium and thickens cervical

mucous (Hatcher et al., 2004). However, simply inhibiting ovulation does not appear to

be the cure-all for PMS sufferers.

Research has found that oral contraceptives containing estrogen are often effective in

alleviating physical symptoms, but not psychoemotional symptoms, and add insult to

injury by decreasing sexual interest (Backstrom et al., 2003; Graham & Sherwin, 1992).

Progesterone-only contraceptives all seem to result in negative mood changes and

physical symptoms (Backstrom et al., 2003). In general various treatments using

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PMS and OCs

estrogens and progestogens have produced inconsistent results with regard to alleviating

PMS symptoms (Bancroft & Rennie, 1993; Hatcher et al., 2004; Jones & Lopez, 2006).

What role do oral contraceptives play in the experience of PMS? Evidence from

studies examining the effects of postmenopausal, or post-oophorectomy hormone

replacement therapy (HRT), point to a primarily neurochemical basis for PMS

(Backstrom et al., 2003; Casper et al., 1990). Literature indicates an interaction between

hormones and the brain’s response systems. Women with a history of PMS, who had

undergone both a surgical oophorectomy and a hysterectomy, could be safely be given

estrogen-only replacement therapy without experiencing a reoccurrence of symptoms

(Feeman et al., 2001).

With regard to GnRH agonist therapy, women whose symptoms improved

significantly all suffered a reoccurrence of PMS when estrogen and progesterone add-

back therapy was administered (Mortola, Girton, & Fischer, 1991; Mezrow et al., 1994).

It is the combination of estrogen and progestin that appears responsible for the experience

of symptoms associated with PMS. Estrogen alone does not appear to create PMS

symptoms. The question then is, why not just use estrogen only pills? There is, in fact, a

very good reason not to. Due to the strong correlation between estrogen replacement

therapy (ERT) and endometrial cancer, adding progestogen is advised due to studies

indicating that its addition significantly decreases the risk for such cancers (Jones &

Lopez).

In conclusion, PMS symptoms are not solely the result of hormonal fluctuations due to

a woman’s menstrual cycle. This is why women with a history of PMS still experience

symptoms even when their hormonal systems are kept in homeostasis and they are not

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PMS and OCs

ovulating. The mechanisms producing PMS are much more complex than that. The

experience of PMS is due to the way in which certain women’s bodies process

neurochemical agents, in particular the combination of estrogen and progesterone.

However there does seem to be a degree of psychosomatic influence indicated by high

placebo response rates in many studies on the treatment of PMS and PMDD (Freeman &

Rickels, 1999; Freeman et al., 2001; Yonkers, Clark & Trivedi, 1997).

Is the end of menstruation and PMS in the foreseeable future? With recent

advances in oral contraceptive technology, such a possibility may already be a reality. As

far as eliminating menstruation, there are already a few products on the market such as

Seasonale that can be taken for 84 consecutive days. After the 84 days of taking the pill,

seven days of placebo pills are given to promote a progesterone cycle withdrawal bleed.

Even in the light of side effects such as spotting, in 2004 sales for Seasonale were around

$87 million (George, 2005).

Two new oral contraceptives, Anya and Belara both promise to give women complete

choice over menstruation. Both can be taken 365 days a year without the need for

placebos. Unless the user wants to experience a withdrawal bleed, which they could for a

variety of reasons, they do not have to (Bitzer, 2005; George, 2005). Although both

Anya and Belara claim to lessen, or even eliminate symptoms associated with PMS,

further research is needed to ascertain whether both forms of contraceptive can actually

live up to that claim. As we have learned, simply producing a state of anovulation and

amenorrhea does not necessarily translate into an absence of PMS. Although our

understanding of PMS continues to advance, it is evident that we still have a lot to learn.

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PMS and OCs

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